Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

Brief Title

Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

Official Title

R34 Pilot Feasibility Randomized, Noninferiority, Cross-Over Trial of Once-Weekly vs. Thrice-Weekly Prophylaxis With Recombinant Factor VIII in Adults With Severe Hemophilia A

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.

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Number of Bleeds

Secondary Outcome

 Inter-dose Hypocoagulability by Thrombin Generation

Condition

Severe Hemophilia A

Intervention

rF.VIII

Study Arms / Comparison Groups

 Arm A

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

July 2012

Completion Date

November 2013

Primary Completion Date

November 2013

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

Gender

Male

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Margaret V. Ragni, MD, MPH, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT01405742

Organization ID

PRO10020178

Secondary IDs

R34HL105870-01A1

Responsible Party

Principal Investigator

Study Sponsor

University of Pittsburgh

Collaborators

 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Margaret V. Ragni, MD, MPH, Principal Investigator, University of Pittsburgh

Verification Date

September 2016