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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2011

Interventions

  • Biological: Human-cl rhFVIII
    • 50 IU/kg for PK dose
  • Biological: Kogenate FS
    • 50 IU/kg for PK dose

Arms, Groups and Cohorts

  • Experimental: Human-cl rhFVIII
  • Active Comparator: Kogenate FS

Clinical Trial Outcome Measures

Primary 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.
    • 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 Measures

  • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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
    • 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).

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 12 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Octapharma
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sigurd Knaub, PhD, Study Director, Octapharma

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