- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01027364
Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B
B-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant, Long-acting Coagulation Factor IX Fc Fusion Protein (rFIXFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia B
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia
- Research Site
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South Australia
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Adelaide, South Australia, Australia
- Research Site
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Western Australia
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Perth, Western Australia, Australia
- Research Site
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Bruxelles, Belgium
- Research Site
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Leuven, Belgium
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Campinas, Brazil
- Research Site
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Vancouver, Canada
- Research Site
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Alberta
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Calgary, Alberta, Canada
- Research Site
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Ontario
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Toronto, Ontario, Canada
- Research Site
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Quebec
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Montreal, Quebec, Canada
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Beijing, China
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Guangzhou, China
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Shanghai, China
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Tianjin, China
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Lyon, France
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Marseille, France
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Berlin, Germany
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Bonn, Germany
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Pokfulam, Hong Kong
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Shatin, Hong Kong
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Bangalore, India
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Pune, India
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Punjab
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Ludhiana, Punjab, India
- Research Site
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Tamil Nadu
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Vellore, Tamil Nadu, India
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Firenze, Italy
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Milano, Italy
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Kasihara-City, Japan
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Kawasaki City, Japan
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Kitakyushu, Japan
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Nagoya, Japan
- Research Site
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Suginami-ku, Japan
- Ressearch Site
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Tokyo, Japan
- Research Site
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Lodz, Poland
- Research Site
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Warszawa, Poland
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Moscow, Russian Federation
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St. Petersburg, Russian Federation
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Gauteng
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Johannesburg, Gauteng, South Africa
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Western Cape
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Cape Town, Western Cape, South Africa
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Malmö, Sweden
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Stockholm, Sweden
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Cambridge, United Kingdom
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London, United Kingdom
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Arizona
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Phoenix, Arizona, United States
- Research Site
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California
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Sacramento, California, United States
- Research Site
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Colorado
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Aurora, Colorado, United States
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Illinois
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Chicago, Illinois, United States
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Indiana
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Indianapolis, Indiana, United States
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Michigan
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East Lansing, Michigan, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Washington
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Seattle, Washington, United States
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and 12 years of age and older and weigh at least 40 kg
- Diagnosed with hemophilia B (baseline Factor IX level less than or equal to 2%)
- History of at least 100 exposure days to any Factor IX product
- Platelet count ≥100,000 cells/μL
Exclusion Criteria:
- History of Factor IX inhibitors
- Kidney or liver dysfunction
- Diagnosed with another coagulation defect other than hemophilia B
- Prior history of anaphylaxis associated with any Factor IX or intravenous (IV) immunoglobulin administration
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Fixed Weekly Interval
50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling. |
Other Names:
Other Names:
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Experimental: Individualized Interval
100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated.
Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.
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Other Names:
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Experimental: On Demand
20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes
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Other Names:
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Experimental: Surgery
The surgical period and dosing are dependent on the type of surgery the participant undergoes.
Participants who started the study in one of the other treatment arms prior to surgery will return to the original treatment arm.
Participants who joined the study in the Surgery arm will be assigned to one of the other treatment arms following post-operative rehabilitation.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Time Frame: up to 52 weeks ± 1 week
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Clinical laboratory evaluations included hematology and blood chemistry.
Table does not include laboratory tests evaluated during the surgical/rehabilitation period.
Because the perioperative management period represents a unique clinical situation, safety data obtained during the surgical/rehabilitation period for participants in Arm 4 were included in listings and reviewed separately.
Review of the listing was sufficient to assess this endpoint.
ULN=upper limit of normal.
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up to 52 weeks ± 1 week
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: up to 52 weeks + 30 days ± 1 week
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AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not.
TE=event present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or not present prior to receiving the first injection but subsequently appeared before last visit on study.
Serious AE (SAE)=AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.
Related=related, possibly related, and relationship missing.
Data include AEs emergent during the surgical/rehabilitation period; AE data are included in each treatment arm only for the time each participant was enrolled in that arm.
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up to 52 weeks + 30 days ± 1 week
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Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) During the Surgical / Rehabilitation Period
Time Frame: up to 52 weeks + 30 days ± 1 week
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AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not.
TEAE=AE present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or was not present prior to receiving the first injection but subsequently appeared before last visit on study.
Participants are counted once if they report multiple events in the same system organ class (SOC) or preferred term (PT).
Coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 15.0 dictionary.
The following SOCs are abbreviated in the table: Immune System (IS); Injury, Poisoning, and Procedural (IPP); Metabolism and Nutrition (MN); Musculoskeletal and Connective Tissue (MCT); Respiratory, Thoracic and Mediastinal (RTM); Skin and Subcutaneous Tissue (SST).
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up to 52 weeks + 30 days ± 1 week
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Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Surgical / Rehabilitation Period
Time Frame: up to 52 weeks + 30 days ± 1 week
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SAE=AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.
TESAE=SAE present prior to receiving the first injection of BeneFIX or rFIXFc that subsequently worsened in severity or was not present prior to receiving the first injection but subsequently appeared before last visit on study.
Participants are counted once if they report multiple events in the same system organ class (SOC) or preferred term (PT).
Coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 15.0 dictionary.
The following SOC is abbreviated in the table: Injury, Poisoning, and Procedural (IPP).
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up to 52 weeks + 30 days ± 1 week
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Incidence Rate of FIX Inhibitor Development
Time Frame: up to 52 weeks ± 1 week
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An inhibitor test result ≥0.6 Bethesda units (BU)/mL, identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive.
Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory.
The incidence rates along with the 95% CI were summarized for all titers for subjects with 50 or more exposure days (EDs) to rFIXFc and a valid inhibitor test after the 50th exposure.
In addition, the incidence rates for all subjects regardless of their exposure days to rFIXFc were also summarized.
The 95% CI was calculated using Clopper-Pearson exact method.
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up to 52 weeks ± 1 week
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Annualized Bleeding Rate
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)*365.25.
In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed pharmacokinetic (PK) sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Comparison of Annualized Bleeding Rates
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Estimated with a factor for arm, based on whole study duration for all participants.
Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)*365.25.
In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later.
The EP was interrupted for the repeat PK period in Arm 1 and for all surgical/rehabilitation periods in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Participant Assessment of Response to Injections to Treat a Bleeding Episode
Time Frame: up to 52 weeks ± 1 week
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Participant's assessment of the response to the first rFIXFc injection for each bleeding episode.
Percentages were based on the number of bleeding episodes for which a response was provided for the first injection, using the following 4-point scale: excellent=abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after the initial injection; good=definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an injection, but possibly requiring more than one injection after 24 to 48 hours for complete resolution; moderate=probable or slight beneficial effect within 8 hours after the initial injection and requiring more than one injection; no response=no improvement, or condition worsened, within approximately 8 hours after the initial injection.
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up to 52 weeks ± 1 week
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Physicians' Global Assessments of Participants' Response to Treatment With rFIXFc
Time Frame: up to 52 weeks ± 1 week
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Physicians assessed each participant's response to rFIXFc using a 4-point scale: excellent=bleeding episodes responded to less than or equal to the usual number of injections or less than or equal to the usual dose of rFIXFc, or the rate of breakthrough bleeding during prophylaxis was less than or equal to that usually observed; effective=most bleeding episodes responded to the same number of injections and dose, but some required more injections or higher doses, or there was a minor increase in the rate of breakthrough bleeding; partially effective=bleeding episodes most often required more injections and/or higher doses than expected, or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; ineffective=routine failure to control hemostasis or hemostatic control required additional agents.
Percentage of the total count of scale responses for all participants is presented.
Multiple responses per participant are counted.
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up to 52 weeks ± 1 week
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Annualized rFIXFc Consumption Per Participant
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Consumption is calculated for the efficacy period (EP).
In Arms 1 and 2, the EP started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
Overall units (IU/kg) of annualized rFIXFc consumption = [Total rFIXFc IU/kg received during the EP / number of days in EP]*365.25.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Average Weekly Dose For the Fixed Weekly Interval Prophylaxis Arm
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Average weekly dose = (total IU/kg of all eligible prophylactic doses in the included intervals / total number of days in the included intervals)*7.
Eligible dose = the first of the 2 doses defining the interval.
Participants could have multiple prophylactic dose changes.
Prophylactic dosing = from first prophylactic injection received for rFIXFc to the last prophylactic injection on study.
Intervals between 2 prophylactic doses separated by a bleed/surgery/PK visit were not included.
In Arm 1, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries).
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Average Dosing Interval For the Individualized Interval Prophylaxis Arm
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Average dosing interval = sum of days in the included dosing intervals divided by the number of included intervals.
Participants could have multiple prophylactic dose interval changes.
Prophylactic dosing = from first prophylactic injection received for rFIXFc to the last prophylactic injection on study.
Intervals between 2 prophylactic doses separated by a bleed/surgery/PK visit were not included.
In Arm 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
The EP was interrupted for all surgical/rehabilitation periods (for both major and minor surgeries).
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Annualized Bleeding Rate by Type of Bleed (Spontaneous and Traumatic)
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Annualized bleeding episodes = (number of bleeding episodes/number of days in efficacy period)*365.25.
Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
Any bleeding at a different location was a separate bleeding episode regardless of time from the last injection.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa)
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Annualized bleeding episodes = (number of bleeding episodes/number of days in efficacy period)*365.25.
Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
Any bleeding at a different location was a separate bleeding episode regardless of time from the last injection.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Number of Days From Last Injection to Treat a New Bleeding Episode
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Please see the definition of the Efficacy Period (EP) in the Outcome Measure 4 Description.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A follow-up injection administered >72 hours after the most recent injection given to treat a bleed was considered a new bleed at the same location and was classified as type=Unknown (bleeding episodes of this type were not evaluable).
The first bleed for each participant could not be included in this analysis since there was no previous bleed from which to measure time.
The number of days from the last injection to treat a bleed to a new bleeding episode was analyzed across all evaluable bleeding episodes per participant.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Number of Injections Required for Resolution of a Bleeding Episode
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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In Arms 1 and 2, the efficacy period (EP) started with date and time of first prophylactic dose following a completed PK sampling period and ended with last dose administered (for prophylaxis or a bleeding episode).
In Arm 3, the EP started following last PK sampling timepoint and ended with either date of last contact or date of last entry into the eDiary, whichever was later.
The EP was interrupted for the repeat PK period in Arm 1 and for all surgical/rehabilitation periods in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
All injections given from the initial sign of a bleed until the last date/time within the bleed window are counted.
The resolution of a bleed is defined as no sign of bleeding following injection for the bleed.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
All injections given from the initial sign of a bleed until the last date/time within the bleed window were counted.
The resolution of a bleed was defined as no sign of bleeding following injection for the bleed.
Bleeding episodes that presented in multiple locations are included as a single event in the overall summary for the number of injections to resolve that bleeding episode but are included in summaries for each location.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed
Time Frame: up to 52 weeks ± 1 week (efficacy period as defined in description)
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For each bleeding episode at one location, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode.
Please see the definition of the efficacy period (EP) in the Outcome Measure 4 Description.
The EP was interrupted for the repeat PK period in Arm 1 (sequential PK subgroup) and for all surgical/rehabilitation periods (for both major and minor surgeries) in all 3 arms.
A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode.
Bleeding episodes that presented in multiple locations are included as a single event in the overall summary for dose administered to resolve that bleeding episode but are included in the individual summaries for each location.
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up to 52 weeks ± 1 week (efficacy period as defined in description)
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Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 26
Time Frame: Baseline, Week 26
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The Haem-A-QoL consists of items pertaining to 10 domains specific to living with hemophilia and was administered to adult participants (> 17 years).
The areas covered by this instrument are: physical health, feeling, view of yourself, sports/leisure, school/work, dealing with hemophilia, and treatment (all 7 domains, during the last month) and future, family planning, and outlook for the future (all 3 domains, recently).
Changes from baseline for the Haem-A-QoL questionnaire are summarized by prestudy treatment regimen (pooled for Arms 1 and 2).
Lower scores represent better QoL; therefore, a negative change from baseline represents improvement during the course of the study.
Scores on a scale range between 0 and 100.
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Baseline, Week 26
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Haem-A-QoL Questionnaire for Adults: Change From Baseline to Week 52
Time Frame: Baseline, Week 52
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The Haem-A-QoL consists of items pertaining to 10 domains specific to living with hemophilia and was administered to adult participants (> 17 years).
The areas covered by this instrument are: physical health, feeling, view of yourself, sports/leisure, school/work, dealing with hemophilia, and treatment (all 7 domains, during the last month) and future, family planning, and outlook for the future (all 3 domains, recently).
Changes from baseline for the Haem-A-QoL questionnaire are summarized by prestudy treatment regimen (pooled for Arms 1 and 2).
Lower scores represent better QoL; therefore, a negative change from baseline represents improvement during the course of the study.
Scores on a scale range between 0 and 100.
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Baseline, Week 52
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Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 26 and Week 52
Time Frame: Baseline, Week 26, Week 52
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The Haemo-QoL, a quality of life (QoL) assessment instrument for children and adolescents with hemophilia, was administered to participants from 13- to 17-years-old.
This instrument assesses domains specific to living with hemophilia.
For the Haemo-QoL, higher scores indicate a worse quality of life.
Scores on a scale range between 0 and 100.
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Baseline, Week 26, Week 52
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Investigators'/Surgeons' Assessment of Participants' Response to rFIXFc for Major Surgery
Time Frame: up to 52 weeks ± 1 week
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Based on the first assessment of hemostasis by the surgeon/investigator 24 hours or later post-surgery.
Scaled responses: Excellent = 1, Good = 2, Fair = 3, Poor/none = 4.
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up to 52 weeks ± 1 week
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Number of Injections Required to Maintain Hemostasis During Major Surgery
Time Frame: up to 52 weeks ± 1 week
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The number of injections to maintain hemostasis during surgery includes all injections for surgery purposes including the loading dose to the end date/time of surgery.
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up to 52 weeks ± 1 week
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Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery
Time Frame: up to 52 weeks ± 1 week
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Mean dose per injection is the average dose for all injections (including loading dose) needed to maintain hemostasis during surgery.
Total dose is the sum across all injections (including loading dose) needed to maintain hemostasis during surgery.
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up to 52 weeks ± 1 week
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Estimated Total Blood Loss During Major Surgery
Time Frame: up to 52 weeks ± 1 week
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up to 52 weeks ± 1 week
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Number of Transfusions Required Per Surgery
Time Frame: up to 52 weeks ± 1 week
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Number of blood component transfusions during a single surgery.
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up to 52 weeks ± 1 week
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Maximum Concentration (Cmax)
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Maximum concentration during a dosing interval.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Area Under the Curve (AUC) Per Dose
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Dose normalized area under the drug concentration-time curve.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Half Life (t1/2) Alpha and t1/2 Beta
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Time required for the concentration of the drug to reach half of its original value.
Alpha and beta half-life indicate distribution and elimination half-life in a two-compartment PK model.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Clearance (CL)
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Mean Residence Time (MRT)
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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The average time for all the drug molecules to reside in the body.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Volume in Steady State (Vss)
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Volume of distribution at steady state.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Incremental Recovery
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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IU/dL rise in plasma per IU/kg drug administered.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Time to 1% and 3% FIX Activity
Time Frame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Time to reach 1 or 3 IU/dL (%) after a single dose.
Assessment of FIX activity with BeneFIX was conducted following a required 120-hour (5-day) washout period, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 72 (±3) hours, and 96 (±3) hours (4 days) from the start of the injection.
Assessment of FIX activity and rFIXFc concentration was conducted following the initial dose of rFIXFc (after a required 120-hour [5-day] washout period) and at Week 26, at these timepoints: predose, 10 (±2) minutes, 1 hour (±15 minutes), 3 hours (±15 minutes), 6 hours (±15 minutes), 24 (±2) hours, 48 (±2) hours, 96 (±3) hours (4 days), 144 (±3) hours (6 days), 168 (±3) hours (7 days), 192 (±3) hours (8 days), and 240 (±3) hours (10 days) from the start of the injection.
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See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
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Number of Participants With Clinically Relevant Abnormalities or Relevant Changes From Baseline in Vital Signs
Time Frame: up to 52 weeks ± 1 week
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Number of participants with clinically relevant abnormalities or relevant changes from baseline in temperature, pulse (beats per minute [bpm]), systolic blood pressure (SBP), and diastolic blood pressure (DBP) are presented.
Baseline (BL) is defined as the last non-missing evaluable assessment taken prior and closest to the first rFIXFc dose.
Because the perioperative management period represents a unique clinical situation, safety data obtained during the surgical/rehabilitation period for participants in Arm 4 were included in listings and reviewed separately.
Review of the listing was sufficient to assess this endpoint.
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up to 52 weeks ± 1 week
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Coagulation Parameter: Change From Pre-dose Values in Prothrombin Split Fragments 1+ 2 (F 1+2)
Time Frame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
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Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Coagulation Parameter: Change From Pre-dose Values in Thrombin-antithrombin (TAT) Complex
Time Frame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
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Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Coagulation Parameter: Change From Pre-dose Values in D-dimer
Time Frame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Maximum value post-dosing is defined as maximum value over the 1-, 6-, and 24-hour evaluations.
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Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Medical Director, Bioverativ Therapeutics Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 998HB102
- 2009-014295-21 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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