Hemophilia Adult Prophylaxis Study

This study has been terminated.
(study was non-feasible per DSMB)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Margaret Ragni, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01405742
First received: July 25, 2011
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Severe Hemophilia A
Drug: Recombinant factor VIII
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • The primary outcome measure is bleeding frequency. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • A secondary outcome measure is factor usage and cost. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
  • A secondary outcomes is joint range of motion. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
  • A secondary outcome is inter-dose hypocoagulability by thrombin generation. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: No ]
  • A secondary outcome measure is F.VIII and inhibitor formation. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: July 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: rF.VIII once then thrice weekly Drug: 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.
Experimental: Arm B: r.FVIII thrice then once weekly 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01405742

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057-1168
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4206
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, United States, 15213-4306
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37235-7749
United States, Washington
Puget Sound Blood Center
Seattle, Washington, United States, 98104-1256
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Margaret V. Ragni, MD, MPH University of Pittsburgh
  More Information

No publications provided

Responsible Party: Margaret Ragni, Laurel Yasko, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01405742     History of Changes
Other Study ID Numbers: PRO10020178
Study First Received: July 25, 2011
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
Hemophilia
Prophylaxis
Recombinant factor VIII

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014