Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

NCT ID: NCT01405742

Last Updated: 2016-10-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-11-30

Brief Summary

The purpose of this pilot R34 trial is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis comparing once weekly with thrice-weekly recombinant factor VIII. Efficacy will measured by bleeding frequency, factor usage, joint range of motion, cost, quality-of-life, F.VIII level, and inter-dose hypocoagulability by thrombin generation. Safety will be measured by inhibitor formation and bleeding events unresponsive to up to two rescue doses.

Detailed Description

The purpose of this 52-week pilot R34 randomized, open-label, non-inferiority, cross-over study is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis. The primary efficacy endpoint will be bleeding frequency. Secondary endpoints will include factor usage, joint range of motion, cost, quality-of-life, and inter-dose hypocoagulability by thrombin generation time and F.VIII activity will also be determined. Safety will be measured by the frequency of bleeding unresponsive to up to two rescue treatments. Inhibitor formation by anti-F.VIII Bethesda assay, and clinical frequency of thrombosis and allergic reactions will also be assessed. Subject acceptance and adherence to the treatment interventions will be determined; and web-based data entry of case report forms, digital range-of-motion images, and quality-of-life instrument will be implemented. The relation of bleeding frequency to relative inter-dose hypocoagulability, will be assessed by inter-dose thrombin generation time (TGT), endogenous thrombin potential (ETP), and factor VIII levels. Optimal blood sample collection and shipping methods will be determined. For all tests, we will estimate and determine completeness and congruency, in order to determine adjustments or revisions required before initiating a large phase III Randomized clinical trial. All testing will be exploratory, so that we may determine if the test, approach are realistic, and to estimate standard deviations for future power analyses.

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

The intervention for Arm A is 40 IU/kg recombinant factor VIII (rFVIII) by once-weekly intravenous injection for 26 weeks.

Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given thrice-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds.

Group Type: EXPERIMENTAL

rF.VIII

Intervention Type: DRUG

40 IU/kg recombinant factor VIII will be given once-weekly or thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 72 hour washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly or once-weekly, respectively, by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Arm B

The intervention for Arm B is 40 IU/kg recombinant factor VIII (rFVIII) by thrice-weekly intravenous injection for 26 weeks.

Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Group Type: EXPERIMENTAL

rF.VIII

Intervention Type: DRUG

40 IU/kg recombinant factor VIII will be given once-weekly or thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 72 hour washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly or once-weekly, respectively, by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Interventions

rF.VIII

40 IU/kg recombinant factor VIII will be given once-weekly or thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 72 hour washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly or once-weekly, respectively, by intravenous injection until week 52, with up to two rescue doses per week for bleeds

Intervention Type: DRUG

Other Intervention Names

recombinant factor VIII

Eligibility Criteria

Inclusion Criteria

• Adult males 18 years or older
• Severe hemophilia A (F.VIII < 0.01 U/ml)
• At least 150 exposure days to F.VIII products
• No detectable inhibitor
• No history of allergic reaction
• Platelets at least 150,000/ul
• If HIV(+), CD4 at least 200/ul, HIV-VL <48 copies/ml,and cART compliant
• If HCV(+), no splenomegaly,varices,GI bleed,ascites,edema,encephalopathy
• Willingness to comply with cross-over design, randomization schema
• Willingness to keep a personal diary of bleeding frequency and factor use
• Willingness to make every 3 month visits, coagulation testing at wks 2, 28

Exclusion Criteria

• Acquired hemophilia
• Any bleeding disorder other than hemophilia A
• Presence of an inhibitor to factor VIII
• Historic platelet count < 100,000
• Use of experimental drugs
• Surgery anticipate in the next 52 weeks
• Symptomatic HCV(splenomegaly,varices,GI bleed,ascites,edema,encephalopathy)
• Symptomatic HIV(CD4<200/ul or HIV VL 48 or more copy/ml,cART noncompliant)
• Life expectancy less than 5 years
• Investigational drug or study within 4 weeks prior to study
• Inability to comply with study requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Margaret Ragni

Laurel Yasko

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Margaret V. Ragni, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Georgetown University

Washington D.C., District of Columbia, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

Puget Sound Blood Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

R34HL105870-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO10020178

Identifier Type: -

Identifier Source: org_study_id