Hemophilia Adult Prophylaxis Study

Severe Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01405742
• Other study ID #: PRO10020178
• Status: Terminated
• Phase: Phase 3
• First received: July 25, 2011
• Last updated: June 5, 2014
• Start date: July 2012
• Est. completion date: November 2013

Study information

• Verified date: June 2014
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• Recombinant factor VIII
In this arm, 40 IU/kg recombinant factor VIII will be given thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 4-day washout period, 40 IU/kg recombinant factor VIII will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds.
• Recombinant factor VIII
In this arm, 40 IU/kg recombinant factor VIII will be given once-weekly by intravenous injection for 26 weeks, with up to two rescue doses per week for bleeds. At 26 weeks after a 4-day washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly by intravenous injection until week 52.

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania
United States	Puget Sound Blood Center	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure is bleeding frequency.		The time frame is 52 weeks per subject.	Yes
Secondary	A secondary outcome measure is factor usage and cost.		The time frame is 52 weeks per subject.	Yes
Secondary	A secondary outcomes is joint range of motion.		The time frame is 52 weeks per subject.	Yes
Secondary	A secondary outcome is inter-dose hypocoagulability by thrombin generation.		The time frame is 52 weeks per subject.	No
Secondary	A secondary outcome measure is F.VIII and inhibitor formation.		The time frame is 52 weeks per subject.	Yes