Severe Hemophilia APhase 3NCT01405742
Hemophilia Adult Prophylaxis Study: Factor VIII in Severe Hemophilia A
A Phase 3 study testing rF.VIII in people with Severe Hemophilia A, run by University of Pittsburgh at 6 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- rF.VIII
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2012to Nov 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Vanderbilt University
Nashville, Tennessee, 37235-7749
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4206
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213-4306
Puget Sound Blood Center
Seattle, Washington, 98104-1256
Georgetown University
Washington D.C., District of Columbia, 20057-1168
About this study
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 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.
Read the 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.
- Conditions
- Severe Hemophilia A
- Being tested
- rF.VIII
- Keywords
- Hemophilia, Prophylaxis, Recombinant factor VIII
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rF.VIIIDrug
Also called recombinant factor 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
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | 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. Receives: Drug: rF.VIII |
| Arm B | Experimental | 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 Receives: Drug: rF.VIII |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Bleeds
The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant.
Measured: Weeks 26 (first intervention) and 52 (second intervention)
Secondary outcomes (2)
Inter-dose Hypocoagulability by Thrombin Generation
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.
Measured: The time frame is 52 weeks per subject.
F.VIII Activity
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.
Measured: The time frame is 52 weeks per subject.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2011 (estimated)
- Study startJul 2012
- Primary completionNov 2013
- Study completionNov 2013
Why it stopped: study was non-feasible per DSMB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Severe Hemophilia AStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Margaret Ragni, University of Pittsburgh
- Investigators
- Margaret V. Ragni, MD, MPH, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01405742
- Sponsor's protocol ID
- PRO10020178
- Other IDs
- R34HL105870-01A1
- Status last verified
- Sep 2016
- First submitted
- 25 Jul 2011
- Last updated
- 7 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The data from this trial will be available, pending NIH approval, through BioLINCC https://biolincc.nhlbi.nih.gov.
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01405742
- Acronym / sponsor ID
- PRO10020178
- Conditions
- Severe Hemophilia A
- Keywords
- Hemophilia, Prophylaxis, Recombinant factor VIII
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study was non-feasible per DSMB
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 29 Jul 2011 (estimated)
- Results
- Posted 19 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: rF.VIIIThe 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. |
| Arm B | Experimental | Drug: rF.VIIIThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rF.VIIIAlso: recombinant factor VIII40 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 | Drug | Arm A, Arm B |
Primary outcome
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.
2 secondary outcomes
Inter-dose Hypocoagulability by Thrombin Generation
Time frame: The time frame is 52 weeks per subject.
F.VIII Activity
Time frame: The time frame is 52 weeks per subject.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The data from this trial will be available, pending NIH approval, through BioLINCC https://biolincc.nhlbi.nih.gov.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret V. Ragni, MD, MPH principal investigator
University of Pittsburgh
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rF.VIII in people with Severe Hemophilia A, run by University of Pittsburgh at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Bleeds (time frame: Weeks 26 (first intervention) and 52 (second intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2016.