Study to Determine the Safety and Efficacy of rFIXFc in Previously Untreated Males With Severe Hemophilia B (PUPs B-LONG)

March 15, 2022 updated by: Bioverativ, a Sanofi company

An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc; BIIB029) in the Prevention and Treatment of Bleeding in Previously Untreated Patients With Severe Hemophilia B

The primary objective of the study was to evaluate the safety of recombinant coagulation factor IX Fc fusion protein (rFIXFc, BIIB029) in previously untreated patients (PUPs) with severe hemophilia B. Secondary objectives were to evaluate the efficacy of rFIXFc in the prevention and treatment of bleeding episodes in PUPs, and to evaluate rFIXFc consumption for prevention and treatment of bleeding episodes in PUPs.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Research Site
  • Denmark
      • Aarhus, Denmark, 8200
        • Research Site
  • France
    • Nord
      • Lille, Nord, France, 59037
        • Hopital Cardiologique - CHU Lille
    • Rhone
      • Lyon Cedex 3, Rhone, France, 69437
        • Research Site
  • Ireland
      • Dublin, Ireland, D12 N512
        • Research Site
  • Italy
      • Milano, Italy, 20122
        • Research Site
      • Napoli, Italy, 80122
        • Research Site
      • Parma, Italy, 43126
        • Research Site
      • Roma, Italy, 00165
        • Research Site
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Research Site
  • New Zealand
      • Auckland, New Zealand, 1023
        • Research Site
  • Poland
      • Warszawa, Poland, 02-091
        • Research Site
  • Sweden
      • Malmo, Sweden, 205 02
        • Research Site
  • United Kingdom
      • London, United Kingdom, WC1N3JH
        • Research Site
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Research Site
    • London
      • Whitechapel, London, United Kingdom, E1 1BB
        • Research Site
  • United States
    • California
      • Sacramento, California, United States, 95817
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Research Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Research Site
    • Michigan
      • East Lansing, Michigan, United States, 48823
        • Research Site
      • Traverse City, Michigan, United States, 49684
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Key Inclusion Criteria:

  • Weight >=3.5 kilogram at the time of informed consent.
  • Severe hemophilia B was defined as less than or equal to (<=)2 International Units per deciliter (IU/dL) (<=2 percent [%]) endogenous FIX documented in the medical record or as tested during the Screening Period.

Key Exclusion Criteria:

  • History of positive inhibitor testing. A prior history of inhibitors was defined based on a participant's historical positive inhibitor test using the local laboratory Bethesda value for a positive inhibitor test (that is equal to or above lower limit of detection).
  • History of hypersensitivity reactions associated with any rFIXFc administration.
  • Exposure to blood components or injection with a coagulation factor IX (FIX) concentrate (including plasma derived) other than rFIXFc.
  • Injection with commercially available rFIXFc more than 28 days prior to Screening.
  • More than 3 injections of commercially available rFIXFc prior to confirmation of eligibility.
  • Other coagulation disorders in addition to hemophilia B.
  • Any concurrent clinically significant major disease that, in the opinion of the Investigator, would have made the participant unsuitable for enrollment (example HIV infection with cluster of differentiation 4 (CD4) lymphocyte count less than (<)200 cells/microliter (mcL) or a viral load greater than (>)200 particles/mcL, or any other known congenital or acquired immunodeficiency).
  • Current systemic treatment with chemotherapy and/or other immunosuppressant drugs. Use of steroids for treatment of asthma or management of acute allergic episodes or otherwise life-threatening episodes was allowed. Treatment in these circumstances should not have exceeded a 14-day duration.
  • Participation within the past 30 days in any other clinical study involving investigational treatment.
  • Current enrollment in any other clinical study involving investigational treatment.
  • Inability to comply with study requirements.
  • Other unspecified reasons that, in the opinion of the Investigator or Bioverativ, would have made the participant unsuitable for enrollment.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (>=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX (FIX) levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
Biological: rFIXFc
Adjustments to the dose and interval of rFIXFc was made in this study based on investigator discretion using available pharmacokinetic (PK) data, subsequent FIX trough and peak levels, level of physical activity, and bleeding pattern, in accordance with local standards of care for a prophylactic regimen. There was an option to start study dosing as episodic treatment (on-demand).
Other Names:
  • Alprolix
  • BIIB029
  • recombinant coagulation factor IX Fc fusion protein

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
Time Frame: Up to 3 years
Development of an inhibitor was defined as an inhibitor test result of >= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of >=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
Up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
Time Frame: Up to 3 years
ABR was annualized number of bleeding episodes during efficacy period (EP) per participant normalized to a 1-year interval of time. Bleeding episodes were classified as: spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent strenuous activity; and traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens excluding surgical/rehabilitation periods and large injection intervals (greater than [>]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Annualized Number of Spontaneous Joint Bleeding Episodes
Time Frame: Up to 3 years
Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there is no known contributing factor such as a definite trauma or antecedent "strenuous" activity. Annualized spontaneous joint bleeding episodes=(Total number of spontaneous joint bleeding episodes during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Number of rFIXFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Time Frame: Up to 3 years
Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Total Number of Exposure Days (EDs)
Time Frame: Up to 3 years
An ED was defined as a 24-hour period in which a participant received one or more doses of rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant who did not have a particular injection type were counted as having zero injections for that type.
Up to 3 years
Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Time Frame: Up to 3 years
Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (> 28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Number of Injections of rFIXFc Required to Resolve a Bleeding Episode
Time Frame: Up to 3 years
Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Average Dose Per Injection of rFIXFc Required to Resolve a Bleeding Episode
Time Frame: Up to 3 years
The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Up to 3 years
Change From Baseline in rFIXFc Incremental Recovery (IR)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144
Blood samples were taken at trough and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX activity less than (<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bioverativ, a Sanofi company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Swedish Orphan Biovitrum

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 13, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 20, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 20, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 9, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 15, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 998HB303
  • 2013-003629-27 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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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