An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A

June 24, 2016 updated by: CSL Behring

A Phase I/III Open-label, Multicenter, Crossover Safety, Efficacy and Pharmacokinetic Study of Recombinant Coagulation Factor VIII (rFVIII) Compared to Recombinant Human Antihaemophilic Factor VIII (rFVIII; INN: Octocog Alfa) in Subjects With Hemophilia A, and a Repeat PK, Safety and Efficacy Study

This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study comparing octocog alfa and rVIII-SingleChain. The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK period (Part 3) and also includes a surgical sub-study for subjects enrolled in Parts 2 and 3.

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.
175

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 2
  • 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
      • Nedlands, Australia, WA 6009
        • Study Site
      • Perth, Australia, WA 6000
        • Study Site
  • Austria
      • Graz, Austria, 8036
        • Study Site
      • Vienna, Austria, 1090
        • Study Site
  • Canada
      • New Brunswick, Canada, E2L 4L2
        • Study Site
  • Czech Republic
      • Hradec Králové, Czech Republic, 500 05
        • Study Site
  • Germany
      • Berlin, Germany, 10249
        • Study Site
      • Berlin, Germany, 13353
        • Study Site
      • Bonn, Germany, 53127
        • Study Site
      • Gießen, Germany, 35392
        • Study Site
      • Hamburg, Germany, 20095
        • Study Site
      • Hannover, Germany, 30159
        • Study Site
      • Heidelberg, Germany, 69123
        • Study Site
  • Hungary
      • Debrecen, Hungary, H-4032
        • Study Site
  • Italy
      • Florence, Italy, 50134
        • Study Site
      • Milan, Italy, 20122
        • Study Site
      • Padova, Italy, 35123
        • Study Site
      • Padova, Italy, 35128
        • Study Site
      • Torino, Italy, 10126
        • Study Site
  • Japan
      • Kashihara, Nara, Japan
        • Study Site
      • Kitakyushu, Fukuoka, Japan
        • Study Site
      • Nagoya, Japan, 466-85660
        • Study Site
      • Nishinomiya, Hyogo, Japan
        • Study Site
      • Okayama, Japan, 710-8602
        • Study Site
      • Saitama, Japan
        • Study Site
      • Suginami-ku, Tokyo, Japan
        • Study Site
      • Tokyo, Japan, 160-0023
        • Study Site
  • Lebanon
      • Beirut, Lebanon
        • Study Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 50400
        • Study Site
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Study Site
  • Philippines
      • Cebu City, Philippines, 6000
        • Study Site
      • Davao City, Philippines, 8000
        • Study Site
  • Poland
      • Gdansk, Poland, 80-952
        • Study Site
      • Krakow, Poland, 31-501
        • Study Site
    • Silesia
      • Wroclaw, Silesia, Poland, 50-367
        • Study Site
  • Romania
      • Bucharest, Romania, 011026
        • Study Site
  • Russian Federation
      • Barnaul, Russian Federation, 656038
        • Study Site
      • Kemerovo, Russian Federation, 650066
        • Study Site
  • South Africa
      • Cape Town, South Africa, 7295
        • Study Site
      • Johannesburg, South Africa, 2193
        • Study Site
  • Spain
      • Barcelona, Spain
        • Study Site
      • La Coruna, Spain
        • Study Site
      • Valencia, Spain, 46026
        • Study Site
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • Study Site
      • Donetsk, Ukraine, 830045
        • Study Site
      • Lviv, Ukraine, 79044
        • Study Site
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Study Site
  • United States
    • California
      • Sacramento, California, United States, 95817
        • Study Site
      • San Diego, California, United States, 92103
        • Study Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Study Site
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Study Site
    • Florida
      • Miami, Florida, United States, 33136
        • Study Site
    • Illinois
      • Chicago, Illinois, United States, 60612-3833
        • Study Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Study Site
    • Texas
      • Houston, Texas, United States, 77030
        • Study Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • 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

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Diagnosis of severe hemophilia A defined as <1% FVIII:C documented in medical records.
  • Males between 18 and 65 years of age (Parts 1 and 2).
  • Males between 12 and 65 years of age (Part 3).
  • Subjects who have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

  • Any history of or current FVIII inhibitors
  • Any first order family history of FVIII inhibitors
  • Use of an Investigational Medicinal Product 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 or reference product.
  • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
  • Any known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
  • Platelet count < 100,000/µL at screening.
  • Human immunodeficiency virus (HIV) positive subjects with a CD4 count < 200/mm3, in their medical history or at screening if available results are older than one year. (HIV positive subjects may participate in the study and antiviral therapy are permitted, at the discretion of the Investigator).
  • 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 prior to Day 1.
  • Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Day 1.

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 Factor VIII (rFVIII)
Biological: rVIII-SingleChain
In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.
Other Names:
  • Recombinant Factor VIII (rFVIII)
  • CSL627
Biological: Octocog alfa
In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.
Other Names:
  • Human coagulation factor VIII (rDNA)

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 24 months
The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.
Up to 24 months
Inhibitor Formation to FVIII
Time Frame: Up to 24 months
Number of subjects who develop inhibitors to FVIII
Up to 24 months
Annualized Spontaneous Bleeding Rate
Time Frame: Up to 24 months
The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).
Up to 24 months
Treatment Success During the Peri-operative Surgical Sub-study
Time Frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.
From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

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
AUC0-∞ (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Before infusion and at up to 10 time points within 72 hours of infusion
Cmax (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Before infusion and at up to 10 time points within 72 hours of infusion
Tmax (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.
Before infusion and at up to 10 time points within 72 hours of infusion
Half-life (t1/2) (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion.
Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 10 time points within 72 hours of infusion.
Mean Residence Time (MRT) (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 10 time points within 72 hours of infusion
Clearance (Cl) (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
Clearance (Cl) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Before infusion and at up to 10 time points within 72 hours of infusion
Volume of Distribution at Steady-state (Vss) (Part 1)
Time Frame: Before infusion and at up to 10 time points within 72 hours of infusion
Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Before infusion and at up to 10 time points within 72 hours of infusion
Incremental Recovery (Part 1)
Time Frame: At 30 minutes after infusion
Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
At 30 minutes after infusion
Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds
Time Frame: Up to 24 months
The annualized bleeding rate was derived for each subject as follows: 365.25*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).
Up to 24 months
Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis
Time Frame: During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)
Percentage of bleeding episodes requiring 1, 2, 3 or > 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.
During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incremental Recovery (Part 3)
Time Frame: At 30 minutes after infusion
Incremental recovery of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.
At 30 minutes after infusion
Volume of Distribution at Steady-state (Vss) (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion.
Volume of distribution at steady-state (Vss) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion.
Clearance (Cl) (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion.
Clearance (Cl) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion.
Mean Residence Time (MRT) (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion.
Mean residence time (MRT) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion.
Half-life (t1/2) (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion.
Half-life (t1/2) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion.
Tmax (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion.
Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after an initial and repeat infusion of rVIII-SingleChain.
Before infusion and at up to 12 time points within 96 hours of infusion.
Cmax (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion
Cmax of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion
AUC0-∞ (Part 3)
Time Frame: Before infusion and at up to 12 time points within 96 hours of infusion
AUC0-∞ (AUC from 0 extrapolated to infinity) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Before infusion and at up to 12 time points within 96 hours of infusion

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

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

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.
February 1, 2012

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.
December 1, 2014

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.
December 1, 2014

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).
November 19, 2011

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.
December 5, 2011

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.
December 7, 2011

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.
August 9, 2016

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.
June 24, 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.
June 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_1001
  • 2011-002393-23 (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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings