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-GR
- Lead Sponsor
- Pfizer Inc.
- 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) prior to providing consent at the screening visit for this study.
2. Participants who have documented 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/mL;
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-Spark100 neutralizing antibodies (nAb) titer=1:1 (i.e., positive for nAb), 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 deation or behavior (including alcoholism) or laboratory abnormality that may ncrease 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) based on central laboratory results..
7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) based on central laboratory results.
8. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, hepatic 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). Note: Participants who have a central laboratory test value that is outside the range specified by the exclusion criteria may have the test repeated, by the central laboratory, to determine eligibility; however, the result must be available prior to Baseline Visit /Visit 2.
9. Currently on antiviral therapy for hepatitis B or C.
10. Any participants with a planned surgical procedure requiring FIX surgical prophylactic
factor treatment in the next 15 months.
11. Participants using therapies that are restricted. See Section 6.5.2 for therapies not
allowed during study participation.
12. Previously dosed 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 hepatic 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 units, Fibro Test/FibroSURE >0.48 or AST-to-Platelet Ratio Index (APRI) >1. In the investigator's opinion, if there is concern regarding the FibroTest results due to a confounding medical history (e.g., proteinuria can impact FibroTest result), the investigator can perform a different assessment of liver fibrosis (e.g., FibroScan or APRI) during the screening period.*Please note: if a participant has a known history of Gilbert's syndrome, a FibroTest cannot be used for fibrosis testing. However, the participant could be tested using FibroScan or
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