An Open Label Multi-center Study to Assess the Efficacy and Safety of B-Domain Deleted Recombinant Factor VIII (BDDrFVIII, ReFacto AF) in Patients With Hemophilia A Undergoing Elective Major Surgery - Study 311

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-001579-37-SE
• Date of registration: 09/12/2005
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals, Inc. Clinical Research and Development
• Public title: An Open Label Multi-center Study to Assess the Efficacy and Safety of B-Domain Deleted Recombinant Factor VIII (BDDrFVIII, ReFacto AF) in Patients With Hemophilia A Undergoing Elective Major Surgery - Study 311
• Scientific title: An Open Label Multi-center Study to Assess the Efficacy and Safety of B-Domain Deleted Recombinant Factor VIII (BDDrFVIII, ReFacto AF) in Patients With Hemophilia A Undergoing Elective Major Surgery - Study 311
• Date of first enrolment: 16/02/2006
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-001579-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
- Male subjects with hemophilia A- FVIII:C = 2%
- Age = 12 years
- A negative FVIII inhibitor at both the local laboratory and central laboratory at screening
- A negative past medical history of a FVIII inhibitor
- Previously treated with = 150 exposure days to any Factor VIII product
- The subject will be undergoing elective major surgery that is anticipated to require FVIII infusions and daily FVIII activity monitoring over a period of at least 6 days following surgery
- ALT (SGOT) and AST (SGPT) =5.0 x ULN, and bilirubin =2mg/dL (33 µmol/L)
- Serum albumin = LLN- Serum creatinine =1.25 x ULN- Platelet count = 100,000 /µL
- Absolute CD4 count >200 µL
- PT =1.25 x ULN or INR = 1.5
- Patients receiving therapy for HIV or Hepatitis infection, must be on a stable antiviral regimen at the time of study entry
- The patient should be able to comply with the mandatory 72-hour washout period as specified in the protocol
- The patient should be able to comply with the required inpatient length of
stay including at least 2 days for BI subjects and at least 6 days for all CI
subjects
The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to inclusion criteria.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- A history of FVIII inhibitor (clinical or laboratory based assessment, as defined in the protocol definitions), such as recurrent low titer values. Any measured Bethesda inhibitor titer greater than or equal to 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay
- Presence of a bleeding disorder in addition to hemophilia A
- Treatment with any investigational drug or device within the past 30 days, except for subjects entering from other studies of ReFacto AF
- Prior participation in this study (except for screen failures)
- Regular (e.g. daily, QOD) use of antifibrinolytic agents or medications known to influence platelet function such as aspirin or certain NSAIDs
- Concomitant therapy with immunosuppressive drugs (e.g., IVIG, routine systemic corticosteroids)
- Known hypersensitivity to hamster protein
- Unwilling or unable to follow the terms of the protocol
The Global Medical Monitor should be consulted about prospective subjects with complex clinical or laboratory histories relevant to exclusion criteria.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Male subjects with hemophilia A (FVIII:C =2% confirmed at screening), previously treated with = 150 exposure days to any Factor VIII product, undergoing elective major surgery that is anticipated to require FVIII infusions over a period of at least 6 days following surgery
MedDRA version: 8.1 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII

Intervention(s)

Product Name: ReFacto AF
Product Code: 3082B2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: moroctocog alfa
CAS Number: 284036/24/4
Current Sponsor code: 3082B2
Other descriptive name: Albumin-Free Factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Product Name: ReFacto AF
Product Code: 3082B2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: moroctocog alfa
CAS Number: 284036/24/4
Current Sponsor code: 3082B2
Other descriptive name: Albumin-Free Factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000-

Product Name: ReFacto AF
Product Code: 3082B2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: moroctocog alfa
CAS Number: 284036/24/4
Current Sponsor code: 3082B2
Other descriptive name: Albumin-Free Factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 250-

Product Name: ReFacto AF
Product Code: 3082B2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: moroctocog alfa
CAS Number: 284036/24/4
Current Sponsor code: 3082B2
Other descriptive name: Albumin-Free Factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 2000-

Primary Outcome(s)

Primary end point(s): Efficacy: Assessment of hemostatic efficacy at the end of surgery as determined by the investigator and/or the surgeon using the 4 point ordinal scale below:
a) Excellent – Achieved hemostasis comparable to that expected after similar surgery in a non-hemophilic subject
b) Good – Prolonged time to hemostasis, with somewhat increased bleeding compared to that expected after similar surgery in a non-hemophilic subject
c) Moderate – Obviously delayed hemostasis, but manageable with additional infusions of FVIII
d) None – No hemostatic response
Safety: evaluations will include routine physical and laboratory examinations, including assessment for FVIII inhibitor development, thrombosis and allergic reactions. All adverse events will be recorded

Secondary Objective: - Characterize and compare the total and daily dose of ReFacto AF for both bolus injection and continuous infusion
- Characterize the pharmacokinetics of ReFacto AF in the patient population
- Characterize the pharmacokinetic measurements required for surgical prophylaxis
- Characterize the predicted and estimated actual blood loss and transfusion requirements in the study patient population
- Characterize the variety of regimens used in those patients treated by continuous infusion
- Characterize patient compliance with prescribed regimens in the outpatient setting

Main Objective: Demonstration of the safety and efficacy of ReFacto AF administered by bolus injection or continuous infusion during the perioperative management of patients with hemophilia A undergoing major surgery

Secondary ID(s)

3082B2-311-WW