An Open-label Study To Evaluate Prophylaxis Treatment, And To Characterize The Efficacy, Safety, And Pharmacokinetics Of B-domain Deleted Recombinant Factor Viii Albumin Free (Moroctocog Alfa [Af-cc]) In Children With Hemophilia A

Pfizer28 sites in 13 countries66 target enrollmentDecember 2007

ConditionsHemophilia A

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Hemophilia A
Sponsor: Pfizer
Enrollment: 66
Locations: 28
Primary Endpoint: Mean Annualized Bleed Rate (ABR) by Treatment: On Demand Cohort
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this research study is to determine the effectiveness, safety, and pharmacokinetics (PK) of moroctocog alfa (AF-CC) in previously treated subjects, who are younger than 6 years of age, with severe or moderately severe hemophilia A.

Registry

clinicaltrials.gov

Start Date

December 2007

End Date

April 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Crossover

Sex

Male

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male subjects, aged less than 6 years, with moderately severe to severe hemophilia A.
•A negative FVIII inhibitor titer at screening, and a medical history negative for a past FVIII inhibitor.
•At least 20 exposure days to any FVIII replacement product.
•Adequate hepatic and renal function
•CD4 count \> 400 cells/uL, and if receiving antiviral therapy must be on a stable regimen
•Additional criteria for subjects participating in the PK assessment:
•Male subjects as described immediately above except they must have a FVIII Activity of less than or equal to 1% confirmed by the central laboratory screening test
•Age \< 6 years at time of PK assessment.
•The subject's size is sufficient to permit PK-related phlebotomy.
•The subject is able to comply with the procedures conducted during the PK assessment, including a mandatory 72-hour washout period preceding the PK assessment.

Exclusion Criteria

•A history of FVIII inhibitor.
•Presence of a bleeding disorder in addition to hemophilia A.
•Treatment with any investigational drug or device within 30 days before the time of signing the informed consent form.
•Major or orthopedic surgery planned to occur during the course of the study.
•Regular (e.g., daily, every other day) use of antifibrinolytic agents or medications known to influence platelet function such as aspirin or certain nonsteroidal anti-inflammatory drugs (NSAIDs), or regular, concomitant therapy with immunomodulating drugs (e.g., intravenous immunoglobulin \[IVIG\], routine systemic corticosteroids).
•Known hypersensitivity to hamster protein.

Outcomes

Primary Outcomes

Mean Annualized Bleed Rate (ABR) by Treatment: On Demand Cohort

Time Frame: Day 1 up to Month 6 (OD Cohort, OD Therapy, Period 1); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

ABR for each participant was calculated as the number of bleeds requiring administration of moroctocog alfa (AF-CC) divided by the total therapy duration (in days), then multiplied by 365.25 (days in a year).

Secondary Outcomes

Mean of Moroctocog Alfa (AF-CC) Infusions Administered To Treat Bleeding Episode: All Participants(Day 1 up to Month 24)
Number of Treated Spontaneous Bleeds by Time Interval Between Bleed Onset and Prior Moroctocog Alfa (AF-CC) Prophylaxis Dose: Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Mean Residence Time (MRT) of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Mean Annualized Bleed Rate (ABR) by Treatment: Routine Prophylaxis Cohort(Day 1 up to Month 24 (RP Cohort, Period 1 and Period 2))
Terminal Phase Half Life (t1/2) of Factor VIII (FVIII) Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Incremental Recovery of Factor VIII Activity(Day 1, Month 6)
Area Under the Curve From Time Zero to Last Measurable Concentration (AUClast) of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Steady-State Volume of Distribution (Vss) of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Number of Participants With Treatment Emergent Adverse Events (AEs) According to Severity(Day 1 up to Month 25)
Number of Participants With Incidence of Less Than Expected Therapeutic Effect (LETE): Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Number of Treated Bleeds Classified on Basis of Response to First Infusion of Moroctocog Alfa (AF-CC) as On-Demand Treatment: OD Therapy (OD and RP Cohort)(Day 1 up to Month 24)
Number of Participants Requiring Prophylaxis Regimen Escalation: Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Mean of Total Number Moroctocog Alfa (AF-CC) Infusions Received: Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Mean of Total Number of Infusions of Moroctocog Alfa (AF-CC) Received Per Week to Assess Compliance: Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Maximum Concentration of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Number of Participants With Treatment-Related Adverse Events(Day 1 up to Month 25)
Mean Routine Prophylaxis Dose (IU/kg) of Moroctocog Alfa (AF-CC) Received: Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Mean of Total Number of Days Participants Exposed to Moroctocog Alfa (AF-CC): Routine Prophylaxis Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))
Clearance (CL) of Factor VIII Activity(0.5, 8, 24, 28 and 32 hours post dose on Day 1)
Number of Participants With Confirmed FVIII Inhibitor Development(Day 1 up to Month 24)
Number of Participants With Incidence of Less Than Expected Therapeutic Effect (LETE): On Demand Therapy(Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Day 1 up to Month 6 (OD Cohort, OD Therapy, Period 1); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2))