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

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989196
• Other study ID #: GENA-01
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: September 2012

Study information

• Verified date: September 2019
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: September 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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

Locations

Country	Name	City	State
Bulgaria	Prof. Lissitchkov	Sofia
Germany	Vivantes Klinikum	Berlin
Germany	Medizinische Hochschule	Hannover	Niedersachsen
United States	RUSH University Medical Center	Chicago	Illinois
United States	University of Colorado	Denver	Colorado
United States	UCLA Orthodpedic Hospital	Los Angeles	California
United States	University of Medicine and Dentistry	New Brunswick	New Jersey
United States	University of California, Davis	Sacramento	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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	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.	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	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.	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	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.	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	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.	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	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.	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	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.	From 1st treatment after PK cycle 2 until study end.
Secondary	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).	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