severe to moderately severe hemophilia B <=2% MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: rAAV-Spark100-hFIX-Padua
Product Code: PF-06838435
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FIDANACOGENE ELAPARVOVEC
Current Sponsor code: PF-06838435 (SPK-9001)
C
Sponsors
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Participants must have completed at least 6 months of routine FIX prophylaxis therapy during the lead-in study (C0371004) and have >=50 lifetime exposure days to a FIX protein product (recombinant, plasma-derived or long-acting FIX product). 2. Participants who have moderately severe to severe hemophilia B, defined as FIX:C =11 g/dL; Platelets >=100,000 cells/µL; Creatinine 2.0 mg/dL. 5. Sex: Male. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following for at least time required for 3 consecutive ejaculate samples to test negative for vector shedding: Refrain from donating sperm. PLUS either: Be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR Must agree to use contraception/barrier as detailed below: Agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person 6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Are the trial subjects under 18? no 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 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Anti-AAV-Spark 100 neutralizing antibodies (nAb) titer, above the established threshold of 1:1, performed by a central laboratory during screening. 2. Prior history of inhibitor to FIX or positive inhibitor testing as measured by the central laboratory >=0.6 Bethesda Units (BU) during screening. Clinical signs or symptoms of decreased response to FIX. 3. Known hypersensitivity to FIX replacement product or intravenous immunoglobulin administration. 4. History of chronic infection or other chronic disease that investigator deems as an unacceptable risk. 5. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation or other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior (including alcoholism) or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. 6. Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase(ALP) >2x upper limit of normal (ULN). 7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 8 kPa, Fibro Test/FibroSURE >0.48 or AST-to-Platelet Ratio Index (APRI) >1. 15. Serological evidence of HIV-1 or HIV-2 with CD4+ cell count =200 mm3 and/or viral load >20 copies/mL. 16. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study. 17. Unable to comply with scheduled visits, treatment plan, laboratory tests and other study procedures for up to six years post infusion of PF-06838435 in the investigator’s judgement. 18. Sensitivity to heparin or heparin-induced thrombocytopenia. 19. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or the sponsor’s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate the efficacy of a single infusion of PF-06838435 in male participants >=18 years of age with moderately severe to severe hemophilia B (FIX:C <=2%).;Secondary Objective: - To demonstrate that the use of exogenous FIX is significantly reduced post PF-06838435 infusion. - To compare additional efficacy parameters post PF-06838435 infusion to baseline including use of exogenous FIX, information on bleeding events, and patient reported outcomes - Safety and tolerability of PF-06838435 - Efficacy assessment over the 6 years of the study.;Primary end point(s): •ABR (first 12 month post infusion of PF-06838435) will be compared within subject to pre infusion of PF-06838435 (under SOC FIX prophylaxis replacement regimen). •Steady state FIX:C (Week 12 to Month 12) will be compared to a threshold of 5%. ;Timepoint(s) of evaluation of this end point: month 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •AIR for FIX at first 12 month post infusion of PF-06838435 vs AIR during SOC FIX replacement regimen will be tested for superiority within participant. •FIX consumption, first 12 months post infusion of PF-06838435, similar method as applied to AIR will used to do hypothesis testing on this endpoint. •Number of bleeding events of specific type first 12 months post infusion of PF- 06838435: spontaneous and traumatic, and untreated. Similar method applied to ABR will be used to test these endpoints. •Frequency of target joint bleeds first 12 months post infusion of PF- 06838435 will be summarized. •HJHS for first 12 months post infusion of PF-06838435 will be compared to baseline •PROs endpoints (Haem A Qol, HAL, PGIC H) 12 month post infusion of PF-06838435 will be summarized, and compared/to baseline to assess the improvement from baseline if baseline is available. ;Timepoint(s) of evaluation of this end point: first 12 months post infusion | — |
Countries
Australia, Brazil, Canada, France, Germany, Greece, Israel, Japan, Saudi Arabia, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed