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.
Verified January 2014 by CSL Behring
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01486927
First received: November 19, 2011
Last updated: February 13, 2014
Last verified: January 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01486927

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

  Hide Study Locations
Locations
United States, California
Study Site Recruiting
Sacramento, California, United States, 95817
Contact: Use central contact         
Principal Investigator: Jerry Powell, MD         
United States, Connecticut
Study Site Not yet recruiting
Hartford, Connecticut, United States, 06106
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Principal Investigator: Donna Boruchov         
United States, Florida
Study Site Recruiting
Miami, Florida, United States, 33136
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Principal Investigator: Joanna Davis, MD         
United States, Illinois
Study Site Recruiting
Chicago, Illinois, United States, 60612-3833
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Principal Investigator: Lisa Boggio, MD         
United States, Louisiana
Study Site Recruiting
New Orleans, Louisiana, United States, 70112
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Principal Investigator: Cindy A Leissinger, MD         
United States, Missouri
Study Site Not yet recruiting
Columbia, Missouri, United States, 65212
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Principal Investigator: Thomas Loew, MD         
United States, Nevada
Study Site Recruiting
Las Vegas, Nevada, United States, 89109-2294
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Principal Investigator: Jonathan Bernstein, Dr.         
United States, Texas
Study Site Not yet recruiting
Houston, Texas, United States, 70030
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Principal Investigator: Miguel Escobar, MD         
United States, Wisconsin
Study Site Recruiting
Milwaukee, Wisconsin, United States, 53226
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Principal Investigator: Joan Gill, MD         
Austria
Study Site Recruiting
Graz, Austria, 8036
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Principal Investigator: Peter Neumeister, MD         
Study Site Recruiting
Vienna, Austria, 1090
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Principal Investigator: Ingrid Pabinger-Fasching, Prof.         
Belgium
Study Site Withdrawn
Gent, Belgium, 9000
Study Site Withdrawn
Liège, Belgium, 4000
France
Study Site Not yet recruiting
Lille, France, 59037
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Principal Investigator: Jenny Goudemand, Prof.         
Study Site Not yet recruiting
Lyon, France, 69437
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Principal Investigator: Claude Negrier, MD         
Germany
Study Site Recruiting
Berlin, Germany, 10249
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Principal Investigator: Robert Klamroth, Dr.         
Study Site Recruiting
Hamburg, Germany, 20095
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Principal Investigator: Wolfgang Zeller, MD         
Study Site Recruiting
Hannover, Germany, 30625
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Principal Investigator: Mario von Depka Prondzinski, MD         
Study Site Recruiting
Heidelberg, Germany, 69123
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Principal Investigator: Angela Huth-Kuehne, Dr.         
Italy
Study Site Recruiting
Florence, Italy, 50134
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Principal Investigator: Massimo Morfini, MD         
Study Site Recruiting
Milan, Italy, 20122
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Principal Investigator: Elena Santagostino, MD         
Study Site Not yet recruiting
Padova, Italy, 35123
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Principal Investigator: Ezio Zanon, MD         
Japan
Study Site Recruiting
Kashihara, Japan
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Principal Investigator: Keiji Nogami         
Study Site Recruiting
Kitakyushu, Japan
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Principal Investigator: Tetsuji Sato         
Study Site Not yet recruiting
Kitakyushu, Japan, 807-8555
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Study Site Recruiting
Nishinomiya, Japan
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Principal Investigator: Satoshi Higasa         
Study Site Recruiting
Saitama, Japan
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Principal Investigator: Katsuyoshi Koh         
Study Site Recruiting
Suginami-ku, Japan
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Principal Investigator: Hideji Hanabusa         
Study Site Recruiting
Tokyo, Japan, 160-0023
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Principal Investigator: Katsuyuki Fukutake         
Poland
Study Site Recruiting
Wroclaw, Silesia, Poland, 50-367
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Principal Investigator: Kazimierz Kuliczkowski, Prof.         
Study Site Not yet recruiting
Gdansk, Poland, 80-952
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Principal Investigator: Andrzej Hellmann, Prof.         
Russian Federation
Study Site Withdrawn
Barnaul, Russian Federation, 656099
Study Site Not yet recruiting
Kirov, Russian Federation, 610027
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Principal Investigator: Tatiana Chernova, MD         
Spain
Study Site Recruiting
Barcelona, Spain
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Principal Investigator: Rafael Parra Lopez         
Study Site Recruiting
La Coruna, Spain
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Principal Investigator: Fernanda Lopez Fernandez         
Sweden
Study Site Recruiting
Malmoe, Sweden, 20502
Contact: Use central contact         
Principal Investigator: Erik Berntorp, MD         
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: February 13, 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 April 17, 2014