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

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

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.

Study Overview

• Status: Completed
• Conditions: Severe Haemophilia A
• Intervention / Treatment: Biological: Human-cl rhFVIII

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human-cl rhFVIII; Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval.	Biological: Human-cl rhFVIII; Human-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: May 23, 2013
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: GENA-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No