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

• ClinicalTrials.gov Identifier: NCT00989196
• Recruitment Status: Completed
• First Posted: October 2, 2009
• Results First Posted: January 17, 2014
• Last Update Posted: October 8, 2019
• Sponsor: Octapharma
• Information provided by (Responsible Party): Octapharma

Tracking Information

• First Submitted Date: September 30, 2009
• First Posted Date: October 2, 2009
• Results First Submitted Date: March 1, 2013
• Results First Posted Date: January 17, 2014
• Last Update Posted Date: October 8, 2019
• Study Start Date: May 2010
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2013)

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: September 27, 2019)

• 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).

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia A

Intervention

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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 2, 2012): 22
• Original Estimated Enrollment (submitted: October 1, 2009): 20
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Germany, United States

Administrative Information

• NCT Number: NCT00989196
• Other Study ID Numbers: GENA-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Octapharma
• Original Responsible Party: Sylvia Werner, Associate Director of Clinical Operations, Octapharma
• Current Study Sponsor: Octapharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Sigurd Knaub, PhD; Octapharma

• PRS Account: Octapharma
• Verification Date: September 2019