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

Hemophilia A Clinical Trial

Official title:

A Postauthorization Safety Surveillance Study Of Patients Switching To ReFacto AF From ReFacto Or Other Factor VIII Products In Usual Care Settings

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00884390
• Other study ID #: 3082B2-4432
• Status: Terminated
• Phase: Phase 4
• First received: April 16, 2009
• Last updated: August 20, 2014
• Start date: May 2009
• Est. completion date: March 2013

Study information

• Verified date: August 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The study will be investigating safety in patients who switch to ReFacto AF from ReFacto and other Factor VIII products.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 208
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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.

Locations

Country	Name	City	State
Austria	Pfizer Investigational Site	Wien
Belgium	Pfizer Investigational Site	Brussels
Belgium	Pfizer Investigational Site	Bruxelles
Belgium	Pfizer Investigational Site	Leuven
Denmark	Pfizer Investigational Site	Copenhagen
Finland	Pfizer Investigational Site	Helsinki
Finland	Pfizer Investigational Site	Kuopio
France	Pfizer Investigational Site	Chambray Les Tours Cedex
France	Pfizer Investigational Site	Clermont Ferrand Cedex 1
France	Pfizer Investigational Site	Clermont-Ferrand Cedex 1
France	Pfizer Investigational Site	Le Chesnay
France	Pfizer Investigational Site	Le Kremlin Bicetre Cedex
France	Pfizer Investigational Site	Limoges Cedex 1
France	Pfizer Investigational Site	Lyon Cedex 03
France	Pfizer Investigational Site	Marseille Cedex 05
France	Pfizer Investigational Site	Montmorency
France	Pfizer Investigational Site	Montpellier Cedex 5
France	Pfizer Investigational Site	Nantes
France	Pfizer Investigational Site	Paris Cedex 15
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Bonn
Germany	Pfizer Investigational Site	Bremen
Germany	Pfizer Investigational Site	Dresden
Germany	Pfizer Investigational Site	Frankfurt am Main
Germany	Pfizer Investigational Site	Fulda
Germany	Pfizer Investigational Site	Halle
Germany	Pfizer Investigational Site	Hamburg
Germany	Pfizer Investigational Site	Heidelberg
Germany	Pfizer Investigational Site	Homburg
Germany	Pfizer Investigational Site	Leipzig
Germany	Pfizer Investigational Site	Leipzig
Germany	Pfizer Investigational Site	Magdeburg
Germany	Pfizer Investigational Site	Muenchen
Germany	Pfizer Investigational Site	Muenchen
Germany	Pfizer Investigational Site	Muenster
Germany	Pfizer Investigational Site	Rostock
Germany	Pfizer Investigational Site	Stuttgart
Germany	Pfizer Investigational Site	Wiesbaden
Greece	Pfizer Investigational Site	Athens
Hungary	Pfizer Investigational Site	Budapest
Italy	Pfizer Investigational Site	Firenze
Italy	Pfizer Investigational Site	Ivrea
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Napoli
Italy	Pfizer Investigational Site	Pavia
Italy	Pfizer Investigational Site	Perugia
Italy	Pfizer Investigational Site	Treviso	Castelfranco Veneto
Italy	Pfizer Investigational Site	Udine
Netherlands	Pfizer Investigational Site	Amsterdam
Netherlands	Pfizer Investigational Site	Groningen
Netherlands	Pfizer Investigational Site	Utrecht
Romania	Pfizer Investigational Site	Bucharest
Spain	Pfizer Investigational Site	A Coruna
Spain	Pfizer Investigational Site	Almeria
Spain	Pfizer Investigational Site	Avila
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Caceres
Spain	Pfizer Investigational Site	Cadiz
Spain	Pfizer Investigational Site	Granada
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Malaga
Spain	Pfizer Investigational Site	Malaga
Spain	Pfizer Investigational Site	Palma de Mallorca	Islas Baleares
Spain	Pfizer Investigational Site	Puerto Real	Cadiz
Spain	Pfizer Investigational Site	Valencia
Spain	Pfizer Investigational Site	Valladolid
Spain	Pfizer Investigational Site	Zaragoza
Sweden	Pfizer Investigational Site	Goteborg
Sweden	Pfizer Investigational Site	Malmo
Sweden	Pfizer Investigational Site	Stockholm
United Kingdom	Pfizer Investigational Site	Bangor	Wales
United Kingdom	Pfizer Investigational Site	Birmingham	England
United Kingdom	Pfizer Investigational Site	Edinburgh	Scotland
United Kingdom	Pfizer Investigational Site	London	England
United Kingdom	Pfizer Investigational Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Romania,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	100 exposure days to study medication (approx. 2 years)	Yes
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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).	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	Number of Participants With Breakthrough Bleeds	The number of participants with any breakthrough bleed was reported.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No
Secondary	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.	100 exposure days to study medication (approx. 2 years)	No

External Links

•   To obtain contact information for a study center near you, click here.