Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A

December 5, 2016 updated by: CSL Behring

A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A

This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to < 12 years of age and at least 25 subjects < 6 years of age who have undergone > 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.

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.
84

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
    • Victoria
      • Melbourne, Victoria, Australia, 3052
        • Study Site
  • Austria
      • Linz, Austria, 4020
        • Study Site
      • Vienna, Austria, 1090
        • Study Site
  • France
      • Brest, France, 29609
        • Study Site
      • Le Kremlin Bicetre, France, 94270
        • Study Site
      • Lille Cedex, France, 59037
        • Study Site
      • Nantes, France, 44093
        • Study Site
      • Paris, France, 75015
        • Study Site
  • Georgia
      • Tbilisi, Georgia, 0177
        • Study Site
  • Germany
      • Bonn, Germany, 53127
        • Study Site
      • Bremen, Germany, 28177
        • Study Site
      • Frankfurt/Main, Germany, 60590
        • Study Site
      • Hannover, Germany, 30159
        • Study Site
  • Italy
      • Milano, Italy, 20122
        • Study Site
  • Lebanon
      • Beirut, Lebanon, 11072240
        • Study Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 50400
        • Study Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Study Site
      • Njmegen, Netherlands, 6525 GA
        • Study Site
      • Utrecht, Netherlands, 3584 CX
        • Study Site
  • Philippines
      • Cebu City, Philippines, 6000
        • Study Site
      • Davao City, Philippines, 8000
        • Study Site
  • Poland
      • Rzeszow, Poland, 35-310
        • Study Site
  • Portugal
      • Oporto, Portugal, 4202-451
        • Study Site
  • Romania
      • Timisoara, Romania, 300011
        • Study Site
  • Spain
      • Madrid, Spain, 28046
        • Study Site
  • Switzerland
      • Lucerne, Switzerland, 6000
        • Study Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Study Site
      • Bangkok, Thailand, 10700
        • Study Site
      • Chiang Mai, Thailand, 50200
        • Study Site
      • Khon Kaen, Thailand, 40002
        • Study Site
      • Songkla, Thailand, 90110
        • Study Site
  • Turkey
      • Adana, Turkey, 01330
        • Study Site
      • Istanbul, Turkey, 34098
        • Study Site
      • Izmir, Turkey, 35100
        • Study Site
  • Ukraine
      • Lviv, Ukraine, 79044
        • Study Site
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Study Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Study 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 11 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
  • Males < 12 years of age,
  • Subjects who have received > 50 EDs with a FVIII product,
  • Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
  • Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.

Exclusion Criteria:

  • Any history of or current FVIII inhibitors
  • Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
  • Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
  • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
  • Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
  • Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening,
  • Subjects with serum creatinine values >2 x ULN at Screening,
  • Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1,
  • Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

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: rVIII-SingleChain
Subjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Biological: rVIII-SingleChain
Other Names:
  • CSL627
  • Recombinant Factor VIII single chain

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
Treatment Success
Time Frame: Up to 1 year
Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
Up to 1 year

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 Bleeding Rate
Time Frame: Up to 1 year
The annualized bleeding rate was defined as the number of bleeding episodes requiring treatment divided by the efficacy evaluation period in days, x 365.25, and is presented separately for the on-demand regimen and the prophylaxis regimens.
Up to 1 year
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.
Time Frame: Up to 1 year
Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month
Time Frame: Up to 1 year
Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year
Time Frame: Up to 1 year
Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event
Time Frame: Up to 1 year
Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month
Time Frame: Up to 1 year
Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year
Time Frame: Up to 1 year
Up to 1 year
Incremental Recovery
Time Frame: At 1 hour after the start of infusion
Incremental recovery expressed as (IU/dL)/(IU/kg) corrected for subject's predose plasma FVIII activity measured using the chromogenic substrate assay.
At 1 hour after the start of infusion
Half-life (t1/2) of rVIII-SingleChain
Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Half-life (t1/2) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Area Under the Concentration Curve (AUC)
Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
AUC to the last sample with quantifiable drug concentration (AUC0-t), baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Clearance (Cl) of rVIII-SingleChain
Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Clearance (Cl) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Number of Subjects With Inhibitor Formation to rVIII-SingleChain
Time Frame: At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).
The number of subjects who develop inhibitors to rVIII-SingleChain, defined as a rVIII-SingleChain antibody titer of at least 0.6 Bethesda Units (BU) per mL after receiving study drug.
At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).

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.
CSL Behring

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

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.
March 1, 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 1, 2015

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 1, 2015

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).
March 19, 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.
March 20, 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.
March 21, 2014

Study Record Updates

Last Update Posted (Estimate)

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.
January 27, 2017

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.
December 5, 2016

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.
December 1, 2016

More Information

Terms related to this study

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.
  • CSL627_3002
  • 2012-001336-65 (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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