- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00989196
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia 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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Sofia, Bulgaria
- Prof. Lissitchkov
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Berlin, Germany
- Vivantes Klinikum
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Niedersachsen
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Hannover, Niedersachsen, Germany
- Medizinische Hochschule
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California
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Los Angeles, California, United States, 90007
- UCLA Orthodpedic Hospital
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Sacramento, California, United States, 95817
- University of California, Davis
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Colorado
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Denver, Colorado, United States, 80045
- University of Colorado
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District of Columbia
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Washington, District of Columbia, United States, 20057
- Georgetown University
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Illinois
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Chicago, Illinois, United States, 60612
- Rush University Medical Center
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New Jersey
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New Brunswick, New Jersey, United States, 08903
- University of Medicine and Dentistry
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Human-cl rhFVIII
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50 IU/kg for PK dose
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Active Comparator: Kogenate FS
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50 IU/kg for PK dose
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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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.
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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.
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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.
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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.
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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.
|
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.
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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.
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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.
|
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.
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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.
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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.
|
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.
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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.
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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.
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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.
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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.
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Efficacy of On-demand Treatment of Bleeding Episodes
Time Frame: From 1st treatment after PK cycle 2 until study end.
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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. |
From 1st treatment after PK cycle 2 until study end.
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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
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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).
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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
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Sigurd Knaub, PhD, Octapharma
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GENA-01
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-
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American Thrombosis and Hemostasis NetworkTakeda; CSL Behring; OctapharmaCompletedHemophilia A | Hemophilia B | Hemophilia | Hemophilia A With Inhibitor | Haemophilia | Hemophilia B With Inhibitor | Haemophilia A Without Inhibitor | Haemophilia B Without InhibitorUnited States
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Clinical Trials on Human-cl rhFVIII
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OctapharmaCompletedSevere Hemophilia AUnited States, France, Canada, United Kingdom, India, Georgia, Moldova, Republic of, Poland, Ukraine
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OctapharmaCompletedSevere Haemophilia AFrance, Japan, United States, Canada, Croatia, Finland, Netherlands, North Macedonia, Slovenia
-
OctapharmaCompletedSevere Hemophilia ACanada, United States, France, Spain, Ukraine, United Kingdom, Belarus, Georgia, Germany, India, Italy, Moldova, Republic of, Morocco, Poland, Portugal, Russian Federation, Slovenia
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OctapharmaCompletedSevere Haemophilia AAustria, United Kingdom, Bulgaria, Hungary, Germany, Poland, Romania, Slovakia
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OctapharmaCompletedSevere Hemophilia AUnited States, Bulgaria
-
OctapharmaCompletedSevere Hemophilia AGermany, Austria, United Kingdom, Bulgaria
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OctapharmaTerminated
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HeNan Sincere Biotech Co., LtdCompleted
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Boehringer IngelheimCompleted
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Contour ResearchCompleted