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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by CSL Behring
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01486927
First received: November 19, 2011
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This is an open-label, non-randomized, efficacy, safety and PK study comparing octocog alfa and CSL627. 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 section (Part 3) including a surgical sub-study for subjects enrolled in Parts 2 and 3.


Condition Intervention Phase
Hemophilia A
Biological: Recombinant Factor VIII (rFVIII)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Treatment success [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Subjects will receive treatment for any bleeding episode and the investigator will rate the efficacy of the treatment based on a four point rating scale "excellent, good, moderate or poor/no response".

  • 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) ] [ Designated as safety issue: No ]
    Subjects will receive pre-treatment with rFVIII prior to major surgery. The investigator will rate the efficacy of the treatment based on a four point rating scale of "excellent, good, moderate or poor/no response".

  • Inhibitor formation to FVIII [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Number of subjects who develop inhibitors to FVIII


Secondary Outcome Measures:
  • AUC0-t [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUC0-t of a single infusion of octocog alfa and CSL627

  • AUC0-∞ [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUC0-∞ of a single infusion of octocog alfa and CSL627

  • Percent of area extrapolated [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Percent of area extrapolated of a single infusion of octocog alfa and CSL627

  • Cmax [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Cmax of a single infusion of octocog alfa and CSL627

  • Tmax [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Tmax of a single infusion of octocog alfa and CSL627

  • Elimination constant [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Elimination constant of a single infusion of octocog alfa and CSL627

  • Half-life (t1/2) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Half-life (t1/2) of a single infusion of octocog alfa and CSL627

  • AUMC0-∞ [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUMC0-∞ of a single infusion of octocog alfa and CSL627

  • Mean residence time (MRT) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Mean residence time (MRT) of a single infusion of octocog alfa and CSL627

  • Clearance (Cl) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Clearance (Cl) of a single infusion of octocog alfa and CSL627

  • Volume of distribution at steady-state (Vss) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and CSL627

  • Proportion of bleeding episodes [ Time Frame: Assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 visit ] [ Designated as safety issue: No ]
    Proportion of bleeding episodes requiring one, 2, 3 or > 3 infusions of CSL627 to achieve hemostasis

  • Incremental recovery [ Time Frame: At 30 minutes after infusion ] [ Designated as safety issue: No ]
    Incremental recovery of a single infusion of octocog alfa and CSL627


Estimated Enrollment: 104
Study Start Date: December 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Recombinant Factor VIII (rFVIII) Biological: Recombinant Factor VIII (rFVIII)
In Part 1 of the study, subjects will receive a single infusion of 50 IU/kg of octocog alfa followed by a single infusion of 50 IU/kg CSL627; each infusion will be preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects will receive infusions of CSL627 to prevent or treat bleeding episodes, at a dose and frequency determined by their study doctor (based on the subject's underlying bleeding phenotype).
Other Name: CSL627

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 CSL627 administration.
  • Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of CSL627 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01486927

Contacts
Contact: Clinical Trial Registration Coordinator clinicaltrials@cslbehring.com

  Show 57 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director CSL Behring
  More Information

No publications provided

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01486927     History of Changes
Other Study ID Numbers: CSL627_1001, 2011-002393-23
Study First Received: November 19, 2011
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
Austria: Federal Office for Safety in Health Care
Sweden: Medical Products Agency
Italy: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Japan: Pharmaceuticals and Medical Devices Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Czech Republic: State Institute for Drug Control

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014