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

Phase 2

Completed

• Conditions: Hemophilia A
• Interventions: Biological: Human-cl rhFVIII; Biological: Kogenate FS

• Registration Number: NCT00989196
• Lead Sponsor: Octapharma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-30
• Study First Submitted QC: 2009-10-01
• Study First Posted: 2009-10-02
• Study Start: 2010-05
• Primary Completion: 2011-10
• Study Completion: 2012-09
• Results First Submitted: 2013-03-01
• Results First Submitted QC: 2013-12-16
• Results First Posted: 2014-01-17
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-27
• Last Update Posted: 2019-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Human-cl rhFVIII	Human-cl rhFVIII	-
Kogenate FS	Kogenate FS	-

Primary Outcome Measures

Name	Time	Method
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS	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.

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS	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.
Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS	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.
Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS	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.
Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS	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.
Efficacy of On-demand Treatment of Bleeding Episodes	From 1st treatment after PK cycle 2 until study end.	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.
Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS	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.
Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS	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.
Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study)	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	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).

Trial Locations

Locations (9)

UCLA Orthodpedic Hospital; 🇺🇸 Los Angeles, California, United States

University of Medicine and Dentistry; 🇺🇸 New Brunswick, New Jersey, United States

Prof. Lissitchkov; 🇧🇬 Sofia, Bulgaria

University of California, Davis; 🇺🇸 Sacramento, California, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

Vivantes Klinikum; 🇩🇪 Berlin, Germany

Medizinische Hochschule; 🇩🇪 Hannover, Niedersachsen, Germany

RUSH University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Colorado; 🇺🇸 Denver, Colorado, United States