Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT00884390
Previous Study | Return to List | Next Study

Study Evaluating Safety Of Patients Switching To ReFacto AF In Usual Care Settings

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00884390
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : April 20, 2009
Results First Posted : September 1, 2014
Last Update Posted : September 1, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE April 16, 2009
First Posted Date  ICMJE April 20, 2009
Results First Submitted Date  ICMJE March 20, 2014
Results First Posted Date  ICMJE September 1, 2014
Last Update Posted Date September 1, 2014
Study Start Date  ICMJE May 2009
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2009)
Inhibitor Development [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2014)
  • Annualized Bleeding Rates (ABRs) [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Response Assessment of First On-demand Treatment of New Bleeds [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Number of ReFacto AF Infusions to Treat Each New Bleed [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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).
  • Number of Bleeding Episodes Occurring ≤48 Hours After a Prophylaxis Infusion [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Number of Participants With Breakthrough Bleeds [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    The number of participants with any breakthrough bleed was reported.
  • 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) ]
    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.
  • TFC Following a Prophylaxis Regimen at Baseline for All Participants [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Average Infusion Dose [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Incidence of Less-than-expected-therapeutic Effect (LETE) in the On-demand Setting [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
  • Incidence of Less-than-expected-therapeutic Effect (LETE) in the Prophylaxis Setting [ Time Frame: 100 exposure days to study medication (approx. 2 years) ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Safety Of Patients Switching To ReFacto AF In Usual Care Settings
Official Title  ICMJE A Postauthorization Safety Surveillance Study Of Patients Switching To ReFacto AF From ReFacto Or Other Factor VIII Products In Usual Care Settings
Brief Summary 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE
  • Drug: moroctocog alfa (AF-CC) (ReFacto AF)
    Providing moroctocog alfa (AF-CC) as test article for use during this study.
  • Procedure: Laboratory tests
    Laboratory samples are collected during study visits, in order to collect safety and efficacy data related to the administration of test article.
Study Arms  ICMJE Experimental: ReFacto AF
Interventions:
  • Drug: moroctocog alfa (AF-CC) (ReFacto AF)
  • Procedure: Laboratory tests
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 20, 2014)
208
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2009)
300
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Denmark,   Finland,   France,   Germany,   Greece,   Hungary,   Italy,   Netherlands,   Romania,   Spain,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00884390
Other Study ID Numbers  ICMJE 3082B2-4432
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date August 2014

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