Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A

Severe Haemophilia A Clinical Trial

Official title:

Prospective, Open-label, Multicenter Phase 3b Study to Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01863758
• Other study ID #: GENA-21
• Status: Completed
• Phase: Phase 3
• First received: May 23, 2013
• Last updated: July 5, 2017
• Start date: August 2013
• Est. completion date: January 2015

Study information

• Verified date: July 2017
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment.

Description:

There were 3 phases in this study: (1) An initial pharmacokinetic (PK) assessment in which participants received a single infusion of 60±5 IU/kg of Human-cl rhFVIII; blood samples were collected for 72 hours following the infusion. (2) Prophylactic Treatment-Phase I during which participants received infusions of 30-40 IU/kg of human-cl rhFVIII every other day or 3x/week for 1-3 months. (3) Prophylactic Treatment-Phase II during which the dose and dosing interval were determined individually from data gathered in the initial PK assessment. The maximum dosing interval with a dose of ≤ 60-80 IU/kg that maintains a trough level of ≥ 0.01 IU/mL was determined. Participants were treated for 6 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Severe haemophilia A (FVIII:C < 1%) according to medical history.

• Male patients = 18 years old.

• Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs).

• Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start.

• Immunocompetence (CD4+ count > 200/microliter).

• HIV-negative, if positive, viral load < 200 particles/microliter or < 400,000 copies/mL.

• Freely given written informed consent

Exclusion Criteria:

• Any coagulation disorder other than haemophilia A.

• Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])

• Severe liver or kidney disease.

Related Conditions & MeSH terms

• Hemophilia A
• Severe Haemophilia A

Intervention

Biological:
• Human-cl rhFVIII
Human-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection.

Locations

Country	Name	City	State
Austria	Medical University Vienna	Vienna
Bulgaria	University Multiprofile Hospital for Active Treatment	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment	Varna
Germany	Vivantes Hospital in Friedrichshain	Berlin
Germany	SRH Kurpfalzklinik Heidelberg GMBH	Heidelberg
Hungary	Hungarian National Healthcare Center	Budapest
Hungary	University of Debrecen, Medical and Health Science Center	Debrecen
Poland	University Teaching Hospital in Bialystok, Teaching Department of Hematology with a Subdepartment of Vascular Diseases	Bialystok
Poland	University Clinical Center, Teaching Department of Hematology and Transplantology	Gdansk
Poland	Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology	Torun
Poland	Institute of Hematology and Transfusion Medicine, Depart. of Hemostatic Disorders and Internal Diseases	Warsaw
Romania	Sanador SRL	Bucharest
Romania	Louis Turcanu Emergency Clinical Children's Hospital	Timisoara
Slovakia	University Hospital Saint Cyril and Metod	Bratislava
Slovakia	University Hospital Martin, Department of Hematology and Transfusiology	Martin
United Kingdom	Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center	Basingstoke
United Kingdom	Royal London Hospital, Barts and the London Hemophilia Center	London
United Kingdom	Manchester Royal Infirmary, Department of Clinical Hematology	Manchester
United Kingdom	Royal Hallamshire Hospital	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

Austria,  Bulgaria,  Germany,  Hungary,  Poland,  Romania,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Number of Bleeding Episodes (BE) in Phase II	The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).	Beginning to the end of Phase II (6 months)
Secondary	Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II	The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included.	Beginning to the end of Phase II (6 months)
Secondary	Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With = 2 Treatments/Week	The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included.	Beginning to the end of Phase II (6 months)
Secondary	Median Dosing Interval During Individually Tailored Prophylaxis	The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient	Beginning to the end of Phase II (6 months)
Secondary	Dosage Per Week in Phase II	The mean dosage per week during Phase II of the study are reported.	Beginning to the end of Phase II (6 months)