Hemophilia APhase 4NCT00884390
Study Evaluating Safety Of Patients Switching To ReFacto AF In Usual Care Settings
A Phase 4 study testing moroctocog alfa (AF-CC) (ReFacto AF) and Laboratory tests in people with Hemophilia A, run by Pfizer at 74 sites in 14 countries.
Trial summary
The study will be investigating safety in patients who switch to ReFacto AF from ReFacto and other Factor VIII products. Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- moroctocog alfa (AF-CC) (ReFacto AF) and Laboratory tests
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 74 sitesin 14 countries
- Study dates
- May 2009to Mar 2013
- Phase
- Phase 4
- 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 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male patients greater than or equal to 12 years of age with severe hemophilia A (FVIII:C less than 1%).
- Treatment history of greater than 150 EDs to prior recombinant or plasma-derived FVIII replacement products.
- Transitioning to ReFacto AF from ReFacto or other recombinant or plasma-derived FVIII replacement products.
- Serum albumin greater than or equal to the lower limit of normal (LLN).
- Platelet count greater than or equal to 100,000/µL.
- Prothrombin time (PT) less than or equal to1.25 × ULN, or international normalized ratio (INR) less than or equal to 1.5.
- HIV positive subjects must have a CD4 count greater than 200/µL and HIV viral load less than 200 particles/µL.
Who cannot join
- Presence of any bleeding disorder in addition to hemophilia A.
- A positive FVIII inhibitor, according to the local laboratory, at screening; or any Bethesda Inhibitor Titer greater than 0.6, regardless of the normal range for the testing laboratory.
- Treated with immunomodulatory therapy (including Immune Tolerance Induction [ITI]) during the screening period.
- Prior exposure to moroctocog alfa (AF-CC).
- Known hypersensitivity to hamster protein.
Trial locations and contacts
74 sites in 14 countries.
74 sites in 14 countries
Germany19 sites
Pfizer Investigational Site
Berlin, 10249
Pfizer Investigational Site
Bonn, 53127
Pfizer Investigational Site
Bremen, 28177
Pfizer Investigational Site
Dresden, 01307
Pfizer Investigational Site
Frankfurt am Main, 60596
Pfizer Investigational Site
Fulda, 36043
Pfizer Investigational Site
Halle, 06120
Pfizer Investigational Site
Hamburg, 20246
Pfizer Investigational Site
Heidelberg, 69123
Pfizer Investigational Site
Homburg, 66421
Pfizer Investigational Site
Leipzig, 04103
Pfizer Investigational Site
Leipzig, 04289
Pfizer Investigational Site
Magdeburg, 39112
Pfizer Investigational Site
München, 80336
Pfizer Investigational Site
München, 80337
Pfizer Investigational Site
Münster, 48143
Pfizer Investigational Site
Rostock, 18059
Pfizer Investigational Site
Stuttgart, 70176
Pfizer Investigational Site
Wiesbaden, 65191
Spain15 sites
Pfizer Investigational Site
A Coruña, A Coruna, 15006
Pfizer Investigational Site
Almería, 4009
Pfizer Investigational Site
Ávila, Avila, 05004
Pfizer Investigational Site
Barcelona, Barcelona, 08035
Pfizer Investigational Site
Cáceres, 10003
Pfizer Investigational Site
Cadiz, 11300
Pfizer Investigational Site
Granada, 18012
Pfizer Investigational Site
Madrid, Spain, 28046
Pfizer Investigational Site
Málaga, Malaga, 29010
Pfizer Investigational Site
Málaga, 29011
Pfizer Investigational Site
Palma de Mallorca, Balearic Islands, 07010
Pfizer Investigational Site
Puerto Real, Cadiz, 11510
Pfizer Investigational Site
Valencia, Valencia, 46009
Pfizer Investigational Site
Valladolid, 47012
Pfizer Investigational Site
Zaragoza, Zaragoza, 50009
France11 sites
Pfizer Investigational Site
Chambray-lès-Tours, 37170
Pfizer Investigational Site
Clermont-Ferrand, 63003
Pfizer Investigational Site
Le Chesnay, 78157
Pfizer Investigational Site
Le Kremlin-Bicêtre, 94275
Pfizer Investigational Site
Limoges, 87042
Pfizer Investigational Site
Lyon, 69437
Pfizer Investigational Site
Marseille, 13385
Pfizer Investigational Site
Montmorency, 95160
Pfizer Investigational Site
Montpellier, 34295
Pfizer Investigational Site
Nantes, 44093
Pfizer Investigational Site
Paris, 75743
Italy8 sites
Pfizer Investigational Site
Florence, 50134
Pfizer Investigational Site
Ivrea, Italy, 10015
Pfizer Investigational Site
Milan, 20122
Pfizer Investigational Site
Naples, 80131
Pfizer Investigational Site
Pavia, 27100
Pfizer Investigational Site
Perugia, 06156
Pfizer Investigational Site
Treviso, Castelfranco Veneto, 31033
Pfizer Investigational Site
Udine, 33100
United Kingdom5 sites
Pfizer Investigational Site
Bangor, Wales, LL57 2PW
Pfizer Investigational Site
Birmingham, England, B4 6NH
Pfizer Investigational Site
Edinburgh, Scotland, EH3 9YW
Pfizer Investigational Site
London, England, NW3 2QG
Pfizer Investigational Site
Manchester, M13 9WL
Belgium3 sites
Pfizer Investigational Site
Brussels, Belgium, 1200
Pfizer Investigational Site
Brussels, 1020
Pfizer Investigational Site
Leuven, 3000
Netherlands3 sites
Pfizer Investigational Site
Amsterdam, 1105 AZ
Pfizer Investigational Site
Groningen, 9713 GZ
Pfizer Investigational Site
Utrecht, 3584 CX
Sweden3 sites
Pfizer Investigational Site
Gothenburg, 41345
Pfizer Investigational Site
Malmö, 205 02
Pfizer Investigational Site
Stockholm, 17176
Finland2 sites
Pfizer Investigational Site
Helsinki, 00029 HUS
Pfizer Investigational Site
Kuopio, 70211
About this study
Official title: A Postauthorization Safety Surveillance Study Of Patients Switching To ReFacto AF From ReFacto Or Other Factor VIII Products In Usual Care Settings
The study will be investigating safety in patients who switch to ReFacto AF from ReFacto and other Factor VIII products.
Read the detailed description
The trial was terminated prematurely on 28 March 2013, due to the inability to recruit the planned number of subjects. The decision to terminate the trial was not based on any safety or efficacy concerns and agreement to close the study in March 2013 was agreed with EMA prior to closure activity.
- Conditions
- Hemophilia A
- Being tested
- moroctocog alfa (AF-CC) (ReFacto AF), Laboratory tests
- Keywords
- Hemophilia A
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
moroctocog alfa (AF-CC) (ReFacto AF)Drug
Providing moroctocog alfa (AF-CC) as test article for use during this study.
Laboratory testsProcedure or surgery
Laboratory samples are collected during study visits, in order to collect safety and efficacy data related to the administration of test article.
| Study group | Role | What they receive |
|---|---|---|
| ReFacto AF | Experimental | Not described Receives: Drug: moroctocog alfa (AF-CC) (ReFacto AF); Procedure: Laboratory tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Significant Factor VIII Inhibitor Development
Number of participants with clinically significant FVIII inhibitor development after switching from ReFacto to moroctocog alfa (AF-CC). Clinically significant inhibitors are defined as a central laboratory confirmed positive inhibitor (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay present at 2 consecutive blood draws within a 6-week interval) and within 28 days before the initial or within 28 days following the second positive FVIII inhibitor sample collection one of the following: the need for the participant to administer alternative hemostatic products in order to achieve sufficient efficacy, or ≥2 adverse event reports of decreased drug effect (or other adverse event indicating a decrease in the efficacy of the test article). The blood sample collection for these results must also be between the date of first dose of study medication and 28 days after the last dose of study medication.
Measured: 100 exposure days to study medication (approx. 2 years)
Secondary outcomes (10)
Annualized Bleeding Rates (ABRs)
An ABR for each participant will be calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the Infusion Log Diary case report form), divided by his total therapy duration (in days), then multiplied by 365.25.
Measured: 100 exposure days to study medication (approx. 2 years)
Response Assessment of First On-demand Treatment of New Bleeds
A 4-point scale of assessment of 'on-demand' treatment (administration of an unscheduled bolus infusion of Refacto-AF to stop bleeding) is defined as:
- Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered.
- Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; or, Definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered.
- Moderate: Probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode.
- No Response: No improvement at all between infusions or during the 24-hour interval following an infusion, or condition worsens.
Measured: 100 exposure days to study medication (approx. 2 years)
Number of ReFacto AF Infusions to Treat Each New Bleed
The Infusion Log Diary case report form (CRF) was used to determine the number of test article infusions administered to treat a bleed. This was calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time).
Measured: 100 exposure days to study medication (approx. 2 years)
Number of Bleeding Episodes Occurring ≤48 Hours After a Prophylaxis Infusion
First, the bleed start time from the Infusion Log Diary CRF was used to determine the number of breakthrough bleeds that occurred ≤48 hours after an infusion marked as "Prophylaxis" (which had no associated bleed). If there was more than 1 bleed location (ie, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. If a response was given, or if a bleed time was given, but "On Demand" was not listed as "treatment type", it was still counted as an on-demand bleed for analyses/summaries. Bleeding episodes were not categorized as spontaneous (atraumatic) or traumatic.
Measured: 100 exposure days to study medication (approx. 2 years)
Number of Participants With Breakthrough Bleeds
The number of participants with any breakthrough bleed was reported.
Measured: 100 exposure days to study medication (approx. 2 years)
Total Factor Consumption (TFC) Following a Non-prophylaxis Regimen at Baseline for All Participants
The total amount (in International Units [IU]) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Measured: 100 exposure days to study medication (approx. 2 years)
TFC Following a Prophylaxis Regimen at Baseline for All Participants
The total amount (in IU) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Measured: 100 exposure days to study medication (approx. 2 years)
Average Infusion Dose
The average infusion dose for each participant was calculated as his total factor consumption (in IU) divided by the number of infusions administered. Summary statistics were reported for both of these variables separately for those participants classified at baseline as following an on-demand regimen, and for those on a primary or secondary prophylaxis regimen.
Measured: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the On-demand Setting
The calculation of incidence of on-demand LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the On Demand LETE CRF), and the denominator was the number of bleeding episodes treated in an on-demand setting. This denominator could include new bleeding episodes in prophylaxis participants breakthrough bleeds), and if subsequent on-demand doses for such a bleed met the on-demand LETE criteria, then an on-demand LETE was reported.
Measured: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the Prophylaxis Setting
The calculation of incidence of prophylaxis LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the Prophylactic LETE CRF), and the denominator was the number of routine prophylaxis infusions. Each infusion was classified in the infusion log ("Prophylaxis/ On Demand/ Preventive"), and participants were instructed to select "On Demand" if the infusion was to treat a bleed, even if the participant typically followed a prophylaxis regimen. Only the infusions classified as "Prophylaxis" were counted in this denominator.
Measured: 100 exposure days to study medication (approx. 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: See termination reason in detailed description.
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 Hemophilia AStudies of the same condition, open and under way.
- More trials run by PfizerThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00884390
- Sponsor's protocol ID
- 3082B2-4432
- Status last verified
- Aug 2014
- First submitted
- 16 Apr 2009
- Last updated
- 1 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Postauthorization Safety Surveillance Study Of Patients Switching To ReFacto AF From ReFacto Or Other Factor VIII Products In Usual Care Settings
- ClinicalTrials.gov ID
- NCT00884390
- Acronym / sponsor ID
- 3082B2-4432
- Conditions
- Hemophilia A
- Keywords
- Hemophilia A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 208 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 20 Apr 2009 (estimated)
- Results
- Posted 1 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will be investigating safety in patients who switch to ReFacto AF from ReFacto and other Factor VIII products.
Detailed description
The trial was terminated prematurely on 28 March 2013, due to the inability to recruit the planned number of subjects. The decision to terminate the trial was not based on any safety or efficacy concerns and agreement to close the study in March 2013 was agreed with EMA prior to closure activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ReFacto AF | Experimental | Drug: moroctocog alfa (AF-CC) (ReFacto AF), Procedure: Laboratory tests |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Male patients greater than or equal to 12 years of age with severe hemophilia A (FVIII:C less than 1%).
- Treatment history of greater than 150 EDs to prior recombinant or plasma-derived FVIII replacement products.
- Transitioning to ReFacto AF from ReFacto or other recombinant or plasma-derived FVIII replacement products.
- Serum albumin greater than or equal to the lower limit of normal (LLN).
- Platelet count greater than or equal to 100,000/µL.
Key exclusion criteria (5 listed)
- Presence of any bleeding disorder in addition to hemophilia A.
- A positive FVIII inhibitor, according to the local laboratory, at screening; or any Bethesda Inhibitor Titer greater than 0.6, regardless of the normal range for the testing laboratory.
- Treated with immunomodulatory therapy (including Immune Tolerance Induction [ITI]) during the screening period.
- Prior exposure to moroctocog alfa (AF-CC).
- Known hypersensitivity to hamster protein.
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 |
|---|---|---|
| moroctocog alfa (AF-CC) (ReFacto AF)Providing moroctocog alfa (AF-CC) as test article for use during this study. | Drug | ReFacto AF |
| Laboratory testsLaboratory samples are collected during study visits, in order to collect safety and efficacy data related to the administration of test article. | Procedure or surgery | ReFacto AF |
Primary outcome
Number of Participants With Clinically Significant Factor VIII Inhibitor Development
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of participants with clinically significant FVIII inhibitor development after switching from ReFacto to moroctocog alfa (AF-CC). Clinically significant inhibitors are defined as a central laboratory confirmed positive inhibitor (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay present at 2 consecutive blood draws within a 6-week interval) and within 28 days before the initial or within 28 days following the second positive FVIII inhibitor sample collection one of the following: the need for the participant to administer alternative hemostatic products in order to achieve sufficient efficacy, or ≥2 adverse event reports of decreased drug effect (or other adverse event indicating a decrease in the efficacy of the test article). The blood sample collection for these results must also be between the date of first dose of study medication and 28 days after the last dose of study medication.
10 secondary outcomes
Annualized Bleeding Rates (ABRs)
Time frame: 100 exposure days to study medication (approx. 2 years)
Response Assessment of First On-demand Treatment of New Bleeds
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of ReFacto AF Infusions to Treat Each New Bleed
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of Bleeding Episodes Occurring ≤48 Hours After a Prophylaxis Infusion
Time frame: 100 exposure days to study medication (approx. 2 years)
Number of Participants With Breakthrough Bleeds
Time frame: 100 exposure days to study medication (approx. 2 years)
Total Factor Consumption (TFC) Following a Non-prophylaxis Regimen at Baseline for All Participants
Time frame: 100 exposure days to study medication (approx. 2 years)
TFC Following a Prophylaxis Regimen at Baseline for All Participants
Time frame: 100 exposure days to study medication (approx. 2 years)
Average Infusion Dose
Time frame: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the On-demand Setting
Time frame: 100 exposure days to study medication (approx. 2 years)
Incidence of Less-than-expected-therapeutic Effect (LETE) in the Prophylaxis Setting
Time frame: 100 exposure days to study medication (approx. 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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The CACHE Study: Coronary Artery Care in HaEmophilia
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A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
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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.
Pfizer CT.gov Call Center study director
Pfizer
74 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing moroctocog alfa (AF-CC) (ReFacto AF) and Laboratory tests in people with Hemophilia A, run by Pfizer at 74 sites in 14 countries.
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 7 inclusion and 5 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 1 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 74 sites in Germany, Spain, France, Italy, United Kingdom and 9 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 1 Sep 2014). 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 Participants With Clinically Significant Factor VIII Inhibitor Development (time frame: 100 exposure days to study medication (approx. 2 years)). 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 1 Sep 2014.