Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Octapharma
ClinicalTrials.gov Identifier:
NCT00989196
First received: September 30, 2009
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

This is a clinical study to investigate the pharmacokinetics, efficacy, safety and immunogenicity of human-cl rhFVIII, a newly developed human cell-line derived recombinant FVIII concentrate in previously treated patients with severe Hemophilia A.


Condition Intervention Phase
Hemophilia A
Biological: Human-cl rhFVIII
Biological: Kogenate FS
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of Human-cl rhFVIII, a Newly Developed Human Cell-line Derived Recombinant FVIII Concentrate in Previously Treated Patients With Severe Hemophilia A

Resource links provided by NLM:


Further study details as provided by Octapharma:

Primary Outcome Measures:
  • The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.


Secondary Outcome Measures:
  • Pharmacokinetic Parameter: Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS [ Time Frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion. ] [ Designated as safety issue: No ]
    After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.

  • Efficacy of On-demand Treatment of Bleeding Episodes [ Time Frame: From 1st treatment after PK cycle 2 until study end. ] [ Designated as safety issue: No ]

    After each infusion of IMP and at the end of a BE, the following efficacy assessment is made by the subject (together with the Investigator in case of on-site treatment):

    Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion.

    Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 - 12 hours after an infusion requiring up to 2 infusions for complete resolution.

    Moderate: Probable or slight beneficial effect within approximately 12 hours after the first infusion requiring more than two infusions for complete resolution.

    None: No improvement within 12 hours, or worsening of symptoms, requiring more than 2 infusions for complete resolution.

    The assessment was made at the end of a BE in case more than one infusion was needed.


  • Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study) [ Time Frame: study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for ] [ Designated as safety issue: Yes ]
    Inhibitor activity was determined by the modified Bethesda assay (Nijmegen modification) at study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for some patients who may finish the study before they achieve 50 EDs), with human-cl rhFVIII (i.e. at the study completion visit).


Enrollment: 22
Study Start Date: May 2010
Study Completion Date: September 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Human-cl rhFVIII Biological: Human-cl rhFVIII
50 IU/kg for PK dose
Active Comparator: Kogenate FS Biological: Kogenate FS
50 IU/kg for PK dose

  Eligibility

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

Inclusion Criteria:

  • Severe hemophilia A (FVIII:C <= 1%)
  • Male subjects between 12 and 65 years of age
  • Body weight 25 kg to 110 kg
  • Previously treated with FVIII concentrate for at least 150 EDs

Exclusion Criteria:

  • Other coagulation disorder than hemophilia A
  • Present or past FVIII inhibitor activity
  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: NCT00989196

Locations
United States, California
UCLA Orthodpedic Hospital
Los Angeles, California, United States, 90007
University of California, Davis
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80045
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057
United States, Illinois
RUSH University Medical Center
Chicago, Illinois, United States, 60612
United States, New Jersey
University of Medicine and Dentistry
New Brunswick, New Jersey, United States, 08903
Bulgaria
Prof. Lissitchkov
Sofia, Bulgaria
Germany
Medizinische Hochschule
Hannover, Niedersachsen, Germany
Vivantes Klinikum
Berlin, Germany
Sponsors and Collaborators
Octapharma
Investigators
Study Director: Sigurd Knaub, PhD Octapharma
  More Information

No publications provided

Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT00989196     History of Changes
Other Study ID Numbers: GENA-01
Study First Received: September 30, 2009
Results First Received: March 1, 2013
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Bulgaria: Bulgarian Drug Agency

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 24, 2014