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Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A

This study has been terminated.
(study was non-feasible per DSMB)
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Margaret Ragni, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01405742
First received: July 25, 2011
Last updated: September 16, 2016
Last verified: September 2016

July 25, 2011
September 16, 2016
July 2012
November 2013   (Final data collection date for primary outcome measure)
Number of Bleeds [ Time Frame: Weeks 26 (first intervention) and 52 (second intervention) ]
The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.
The primary outcome measure is bleeding frequency. [ Time Frame: The time frame is 52 weeks per subject. ]
Complete list of historical versions of study NCT01405742 on ClinicalTrials.gov Archive Site
  • Inter-dose Hypocoagulability by Thrombin Generation [ Time Frame: The time frame is 52 weeks per subject. ]
    Thrombin generation was performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52.
  • F.VIII Activity [ Time Frame: The time frame is 52 weeks per subject. ]
    F.VIII Activity (IU/mL) performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52.
  • A secondary outcome measure is factor usage and cost. [ Time Frame: The time frame is 52 weeks per subject. ]
  • A secondary outcomes is joint range of motion. [ Time Frame: The time frame is 52 weeks per subject. ]
  • A secondary outcome is inter-dose hypocoagulability by thrombin generation. [ Time Frame: The time frame is 52 weeks per subject. ]
  • A secondary outcome measure is F.VIII and inhibitor formation. [ Time Frame: The time frame is 52 weeks per subject. ]
Not Provided
Not Provided
 
Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A
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
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.
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.
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Severe Hemophilia A
Drug: 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
Other Name: recombinant factor VIII
  • Experimental: 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.

    Intervention: Drug: rF.VIII
  • Experimental: 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

    Intervention: Drug: rF.VIII
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
November 2013
November 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Male
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01405742
PRO10020178
R34HL105870-01A1 ( US NIH Grant/Contract Award Number )
Yes
Not Provided
Yes
The data from this trial will be available, pending NIH approval, through BioLINCC https://biolincc.nhlbi.nih.gov.
Margaret Ragni, University of Pittsburgh
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Margaret V. Ragni, MD, MPH University of Pittsburgh
University of Pittsburgh
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP