Clinical trial NCT00543439: Study Evaluating Prophylaxis Treatment & Characterizing Efficacy, Safety, & PK Of B-Domain Deleted Recombinant FVIII
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-10-15
Enrollment: 66
Sex: MALE
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Mean Annualized Bleed Rate (ABR) by Treatment: On Demand Cohort
timeFrame: 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)
Secondary outcomes:
measure: Mean Annualized Bleed Rate (ABR) by Treatment: Routine Prophylaxis Cohort
timeFrame: Day 1 up to Month 24 (RP Cohort, Period 1 and Period 2)
measure: Mean of Moroctocog Alfa (AF-CC) Infusions Administered To Treat Bleeding Episode: All Participants
timeFrame: Day 1 up to Month 24
measure: 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)
timeFrame: Day 1 up to Month 24
measure: Number of Treated Spontaneous Bleeds by Time Interval Between Bleed Onset and Prior Moroctocog Alfa (AF-CC) Prophylaxis Dose: Routine Prophylaxis Therapy
timeFrame: 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)
measure: Number of Participants Requiring Prophylaxis Regimen Escalation: Routine Prophylaxis Therapy
timeFrame: 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)
measure: Mean Routine Prophylaxis Dose (IU/kg) of Moroctocog Alfa (AF-CC) Received: Routine Prophylaxis Therapy
timeFrame: 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)
measure: Mean of Total Number Moroctocog Alfa (AF-CC) Infusions Received: Routine Prophylaxis Therapy
timeFrame: 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)
measure: Mean of Total Number of Days Participants Exposed to Moroctocog Alfa (AF-CC): Routine Prophylaxis Therapy
timeFrame: 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)
measure: Mean of Total Number of Infusions of Moroctocog Alfa (AF-CC) Received Per Week to Assess Compliance: Routine Prophylaxis Therapy
timeFrame: 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)
measure: Terminal Phase Half Life (t1/2) of Factor VIII (FVIII) Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Clearance (CL) of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Incremental Recovery of Factor VIII Activity
timeFrame: Day 1, Month 6
measure: Maximum Concentration of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Area Under the Curve From Time Zero to Last Measurable Concentration (AUClast) of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Steady-State Volume of Distribution (Vss) of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Mean Residence Time (MRT) of Factor VIII Activity
timeFrame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) According to Severity
timeFrame: Day 1 up to Month 25
measure: Number of Participants With Treatment-Related Adverse Events
timeFrame: Day 1 up to Month 25
measure: Number of Participants With Confirmed FVIII Inhibitor Development
timeFrame: Day 1 up to Month 24
measure: Number of Participants With Incidence of Less Than Expected Therapeutic Effect (LETE): On Demand Therapy
timeFrame: 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)
measure: Number of Participants With Incidence of Less Than Expected Therapeutic Effect (LETE): Routine Prophylaxis Therapy
timeFrame: 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)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: OHSU Investigational Pharmacy
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: Childrens Medical Center Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Buenos Aires
country: Argentina
facility: Fundacion de la Hemofilia
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Bogota
country: Colombia
facility: Liga Colombiana de Hemofílicos y otras Deficiencias Sanguíneas
city: Split
country: Croatia
facility: Clinical Hospital Centre Split
city: Irbid
country: Jordan
facility: Jordan University of Science and Technology, King Abdullah University Hospital
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Dr. Juan I. Menchaca
state: Jalisco
city: Colonia Centro
country: Mexico
facility: Hospital y Clinica OCA S.A. de C.V.
state: Monterrey, Nuevo LEON
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo LEON
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: South Island
city: Christchurch
country: New Zealand
facility: Canterbury District Health Board
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Urbanización La Victoria
country: Peru
facility: Centro Medico Monte Carmelo
state: Arequipa
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny
city: Bucuresti
country: Romania
facility: Sanador
city: Balcali/Adana
country: Turkey
facility: Cukurova University Tip Fakultesi
state: Adana
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Cocuk Hastanesi
state: Bornova
city: Capa
country: Turkey
facility: Istanbul Universtesi Istanbul Tip Fakultesi
state: Istanbul
city: Samsun
country: Turkey
facility: On Dokuz Mayis University Faculty of Medicine
state: Kurupelit
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Izmir
country: Turkey
facility: Dr. Behcet Uz Child and Diseases And Surgery Education and Research Hospital
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: