Back to resultsClinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Human-cl rhFVIII
Kogenate FS
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility 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
Sites / Locations
- UCLA Orthodpedic Hospital
- University of California, Davis
- University of Colorado
- Georgetown University
- RUSH University Medical Center
- University of Medicine and Dentistry
- Prof. Lissitchkov
- Medizinische Hochschule
- Vivantes Klinikum
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Human-cl rhFVIII
Kogenate FS
Arm Description
Outcomes
Primary Outcome Measures
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS
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
Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS
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
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
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
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
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
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
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)
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00989196
Brief Title
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Human-cl rhFVIII
Arm Type
Experimental
Arm Title
Kogenate FS
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Human-cl rhFVIII
Intervention Description
50 IU/kg for PK dose
Intervention Type
Biological
Intervention Name(s)
Kogenate FS
Intervention Description
50 IU/kg for PK dose
Primary Outcome Measure Information:
Title
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Secondary Outcome Measure Information:
Title
Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS
Description
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 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.
Title
Efficacy of On-demand Treatment of Bleeding Episodes
Description
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.
Time Frame
From 1st treatment after PK cycle 2 until study end.
Title
Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study)
Description
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).
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sigurd Knaub, PhD
Organizational Affiliation
Octapharma
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Orthodpedic Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
RUSH University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Medicine and Dentistry
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Prof. Lissitchkov
City
Sofia
Country
Bulgaria
Facility Name
Medizinische Hochschule
City
Hannover
State/Province
Niedersachsen
Country
Germany
Facility Name
Vivantes Klinikum
City
Berlin
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A
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