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

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.

Condition or disease	Intervention/treatment	Phase
Hemophilia A	Biological: Human-cl rhFVIII; Biological: Kogenate FS	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: May 2010
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: September 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Human-cl rhFVIII	Biological: Human-cl rhFVIII; 50 IU/kg for PK dose
Active Comparator: Kogenate FS	Biological: Kogenate FS; 50 IU/kg for PK dose

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.

8. 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).

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

UCLA Orthodpedic Hospital

Los Angeles, California, United States, 90007

University of California, Davis

Sacramento, California, United States, 95817

United States, Colorado

University of Colorado

Denver, Colorado, United States, 80045

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20057

United States, Illinois

RUSH University Medical Center

Chicago, Illinois, United States, 60612

United States, New Jersey

University of Medicine and Dentistry

New Brunswick, New Jersey, United States, 08903

Bulgaria

Prof. Lissitchkov

Sofia, Bulgaria

Germany

Medizinische Hochschule

Hannover, Niedersachsen, Germany

Vivantes Klinikum

Berlin, Germany

Sponsors and Collaborators

Octapharma

Investigators

• Study Director: Sigurd Knaub, PhD; Octapharma

More Information

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT00989196
• Other Study ID Numbers: GENA-01
• First Posted: October 2, 2009
• Results First Posted: January 17, 2014
• Last Update Posted: October 8, 2019
• Last Verified: September 2019

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Factor VIII; Coagulants