Clinical trial NCT00914459: Study Evaluating Safety And Efficacy Of Moroctocog Alfa (AF-CC) In Previously Treated Hemophilia A Patients
Official title: A Non-randomized, Open-label Study To Evaluate The Pharmacokinetics, Safety And Efficacy Of Refacto Af In Previously Treated Pediatric Subjects Less Than Twelve Years Of Age With Severe Hemophilia A (Fviii:c <1%).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemophilia A
Keywords: hemophilia A
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-06-05
Enrollment: 37
Sex: MALE
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will be investigating pharmacokinetics, safety and efficacy in patients less than 12 years of age with severe hemophilia A that have been previously treated with Factor VIII products ( including blood products).


Eligibility criteria: Inclusion Criteria:

* Male subjects less than 12 years of age with a documented history of severe hemophilia A (FVIII:C less than 1%).
* Subjects who are less than 6 years of age must have had at least 50 Exposure Days (EDs) to prior FVIII products (including blood products).
* Subjects who are equal to or greater than 6 years of age must have had greater than 150 EDs to prior FVIII products (including blood products).

Exclusion Criteria:

* For laboratory assessments, any measured Bethesda inhibitor titer equal to or greater than 0.6 BU, regardless of the laboratory normal range, or any Bethesda inhibitor titer greater than ULN for the testing laboratory at the time of screening.
* Any other bleeding disorder in addition to hemophilia A.
* Treatment with any investigational drug or device within 30 days before the time of signing the parental informed consent/assent form.
* Major surgery planned to occur during the course of the study.
* Regular (e.g., daily; every other day) use of agents or medications known to influence platelet function such as aspirin or certain nonsteroidal anti-inflammatory drugs (NSAIDS).
* Regular, concomitant therapy with immunomodulating drugs (e.g., intravenous immunoglobulin \[IVIG\], routine systemic corticosteroids), or currently receiving immune tolerance induction (ITI) for inhibitor treatment.
* The subject is receiving treatment for HIV or hepatitis infection (unless the subject is on a stable antiviral regimen \[i.e., consistent treatment regimen for at least 3 months before the parental informed consent/assent form is signed\]).
* Platelet count less than 100,000/µL.
* Prothrombin time (PT) equal to or greater than 1.25 x ULN, or international normalized ratio (INR) equal to or greater than 1.5.
* Known hypersensitivity to hamster protein.

Primary outcomes:
measure: Percentage of Participants With Clinically Significant Factor VIII Inhibitor Development
timeFrame: Baseline up to Month 24
measure: Incremental Recovery
timeFrame: Days 1, 15, 50, Months 6, 18 and Final visit (up to Month 24)
measure: Terminal Elimination Half Life of ReFacto AF (t1/2)
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
measure: Clearance (CL)
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
Secondary outcomes:
measure: Mean Annualized Bleeding Rates (ABRs): All Participants
timeFrame: Baseline up to Month 24
measure: Response to First On-Demand Treatment for New Bleeds: All Participants
timeFrame: Baseline up to Month 24
measure: Number of On-Demand ReFacto AF Infusions to Treat a New Bleed: All Participants
timeFrame: Baseline up to Month 24
measure: Number of Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of ReFacto AF: All Participants
timeFrame: Baseline up to Month 24
measure: Average Infusion Dose of ReFacto AF: All Participants
timeFrame: Baseline up to Month 24
measure: Total Factor VIII Consumption: All Participants
timeFrame: Baseline up to Month 24
measure: Number of Less-Than-Expected-Therapeutic Effect (LETE) Bleeds in the On-Demand Setting: All Participants
timeFrame: Baseline up to Month 24
measure: Number of Less-Than-Expected-Therapeutic Effect (LETE) Bleeds in the Prophylaxis Setting: All Participants
timeFrame: Baseline up to Month 24
measure: Number of Occurrences of Less-Than-Expected-Therapeutic Effect (LETE) in the Low Recovery Setting: All Participants
timeFrame: Baseline up to Month 24
measure: Number of Participants Requiring Escalated Dose of Prescribed Regimen During the Treatment Period: All Participants
timeFrame: Baseline up to Month 24
measure: Plasma Concentration of Factor VIII at 0.5 Hour Post-dose (C0.5)
timeFrame: 0.5 hour post-dose on Day 1
measure: Area Under the Plasma Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
measure: Area Under the Plasma Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast)
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
measure: Mean Residence Time (MRT) of ReFacto AF
timeFrame: Pre-dose, 0.5, 1, 3, 6, 9, 24, 28, 32, 48 hours post-dose on Day 1
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): All Participants
timeFrame: Baseline up to 30 days after last study visit (Month 25)
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tbilisi
country: Georgia
facility: LTD Medinvesti- Institute of hematology and transfusiology
city: Parma
country: Italy
facility: Centro di Riferimento Regionale per la cura dell'Emofilia e delle Malattie Emorragiche Congenite
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Craiova
state: Dolj
city: Bucharest
country: Romania
facility: Sanador
city: Belgrade
country: Serbia
facility: University Children's Hospital
city: Belgrade
country: Serbia
facility: Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic"
city: Jerez de la Frontera
country: Spain
facility: Hospital Jerez de la Frontera
state: Cádiz
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Madrid
country: Spain
facility: Hospital La Paz
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset-Solna
city: Adana
country: Turkey
facility: Cukurova University Department of Pediatrics, Pediatric Hematology Division
state: Balcali/adana
city: Izmir
country: Turkey
facility: Ege University Department of Pediatrics, Pediatric Hematology Division
state: Bornova /izmir
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
state: Kampus
city: Lviv
country: Ukraine
facility: Derzhavna ustanova "Instytut patolohii krovi ta transfuziinoi medytsyny Natsionalnoi akademii medych
city: Zaporizhzhia
country: Ukraine
facility: Komunalna ustanova "Zaporizka oblasna klinichna dytiacha likarnia"
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: