Hemophilia Adult Prophylaxis Study
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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 |
- The primary outcome measure is bleeding frequency. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
- 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 ]
| Estimated Enrollment: | 20 |
| Study Start Date: | July 2012 |
| Estimated Study Completion Date: | February 2014 |
| Estimated Primary Completion Date: | December 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 |
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| Contact: Margaret V. Ragni, MD, MPH | 412-209-7288 | ragni@dom.pitt.edu |
| Contact: Kristen Jaworski, BSN, RN | 412-209-7411 | kjaworski@itxm.org |
| United States, District of Columbia | |
| Georgetown University | Not yet recruiting |
| Washington, District of Columbia, United States, 20057-1168 | |
| Contact: Craig Kessler, MD kesslerc@gunet.georgetown.edu | |
| Sub-Investigator: Craig Kessler, MD | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Not yet recruiting |
| Philadelphia, Pennsylvania, United States, 19104-4318 | |
| Contact: Leslie Raffini, MD raffini@email.chop.edu | |
| Sub-Investigator: Leslie Raffini, MD | |
| Hospital of the University of Pennsylvania | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104-4206 | |
| Contact: Patrick Fogarty, MD patrick.fogarty@uphs.upenn.edu | |
| Sub-Investigator: Patrick Fogarty, MD | |
| Hemophilia Center of Western Pennsylvania | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15213-4306 | |
| Contact: Margaret V. Ragni, MD, MPH 412-209-7288 ragni@dom.pitt.edu | |
| Contact: Kristen Jaworski, BSN, RN 412-209-7411 kjaworski@itxm.org | |
| Principal Investigator: Margaret V. Ragni, MD, MPH | |
| United States, Tennessee | |
| Vanderbilt University | Recruiting |
| Nashville, Tennessee, United States, 37235-7749 | |
| Contact: Anne Neff, MD anne.neff@vanderbilt.edu | |
| Sub-Investigator: Anne Neff, MD | |
| United States, Washington | |
| Puget Sound Blood Center | Not yet recruiting |
| Seattle, Washington, United States, 98104-1256 | |
| Contact: Neil Josephson, MD, PhD njoseph@washington.edu | |
| Sub-Investigator: Neil Josephson, MD | |
| 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: | August 5, 2012 |
| 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 May 23, 2013