A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (BeneGene-2)
- Conditions
- severe to moderately severe hemophilia B <=2%MedDRA version: 20.0Level: LLTClassification code 10060614Term: Hemophilia B (Factor IX)System Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-003086-33-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 50
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 <=2%.
3. Participants must agree to suspend prophylaxis therapy for hemophilia B after administration of the IP. FIX replacement therapy is allowed as needed
4. Acceptable screening laboratory values as follows:
Hemoglobin >=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
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 <35%).
8. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease including Gilbert's syndrome, asymptomatic gallstones, is acceptable if the participant otherwise meets entry criteria).
9. Currently on antiviral therapy for hepatitis B or C.
10. Any patient with a planned surgical procedure requiring FIX surgical prophylactic factor treatment in the next 12 months.
11. Patients using therapies that are restricted. See Section 6.5.2 of the Protocol for therapies not allowed during study participation.
12. Prior participation in a gene therapy research trial at any time or in an interventional clinical study within the last 12 weeks, excluding participation in study C0371004.
13. Active hepatitis B or C; HBsAg, HBV-DNA positivity, or HCV-RNA positivity.
14. Significant liver disease, as defined by pre-existing diagnosis of portal hypertension, splenomegaly or encephalopathy. Additionally during screening, a serum albumin level below normal limits and/or significant liver fibrosis by any of the following diagnostic modalities: FibroScan score >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method