A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Pediatric Male Participants With Moderately Severe to Severe Hemophilia B (BeneGene-3)
- Conditions
- moderately severe to severe hemophilia B (FIX:C=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
- EUCTR2020-002443-38-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- Male
- Target Recruitment
- 15
1.Participant must be <18 years of age at the time of signing the informed consent/assent from Study Site.
•For enrollment in Cohort 1, participant must be =12 to <18 years of age.
•Criteria for Cohorts 2 and 3 will be provided at time of future protocol amendment.
2.Participants who have laboratory-documented moderately severe to severe hemophilia B, defined as FIX:C=2%.
3.For Cohort 1, participants who have been on stable routine prophylaxis for at least 1 year.
4.For Cohort 1, participants who have at least 50 documented exposure days to FIX replacement product (recombinant, plasma-derived, or long-acting FIX product).
5.For Cohort 1, participants who have at least 1 year of diary information in which exogenous FIX replacement infusions and hemophilic bleeding episodes were documented in real time as they occurred over the previous 12 months.
6.Participants/legally authorized representatives must agree to suspend prophylaxis therapy for hemophilia B after administration of the study intervention. FIX replacement therapy is allowed as needed.
7.Participants who at screening have:
•Hemoglobin above or equal to the lower limit of normal for age;
•Platelets =100,000 cells/µL;
•Creatinine =1.5 × ULN for age.
8. Male
Sexually active participants must agree to use contraception in accordance with time period specified in the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Anti-AAV-Spark100 nAb titer =1:1 (i.e., positive for nAb), at screening.
2.Participants who have current or prior history of inhibitor to FIX.
3.Known hypersensitivity to FIX replacement product or IV immunoglobulin administration.
4.History of thrombotic events including, but not limited to, stroke or myocardial infarction.
5.History of or any concurrent clinically significant major chronic disease, infection, or condition that the investigator deems unsuitable for participation.
6.ALT, AST, alkaline phosphatase >2 × ULN.
7.Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN 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, hepatic encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
9.Currently on antiviral therapy for hepatitis B or C.
10.Any participant with a planned surgical procedure requiring FIX surgical prophylactic factor treatment in the next 12 months.
11.Participant received any vaccination(s) in the 3 months prior to infusion of study intervention with the exception of nonlive influenza vaccination, which is permissible up to 1 month prior to infusion of study intervention.
12.Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within the last 12 weeks.
13.Active hepatitis B or C; hepatitis B surface antigen positivity, hepatitis B core antibody positivity, hepatitis B virus-DNA positivity, or hepatitis C virus-RNA viral load positivity, respectively.
14.Significant liver disease, as defined by pre-existing diagnosis of portal hypertension, splenomegaly, or hepatic encephalopathy or a serum albumin level below normal limits during screening. Significant fibrosis will be screened for in all participants with testing by FibroTest/FibroSURE (a score of >0.48 is exclusionary), FibroScan (a score of >8 kPa is exclusionary), or shear wave elastography by conventional ultrasound (a score of >6.7 kPa is exclusionary).
15.Serological evidence of HIV-1 or HIV-2 with CD4+ cell count =200/mm3 or viral load >20 copies/mL.
16.Sensitivity to heparin or heparin-induced thrombocytopenia.
17.Sensitivity to the study intervention, or components thereof, or drug or other allergy that, in the opinion of the investigator or the sponsor's Medical Monitor, contraindicates participation in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate efficacy of a single infusion of PF-06838435 (fidanacogene elaparvovec) in male pediatric participants <18 years of age with moderately severe to severe hemophilia B (FIX:C=2%);Secondary Objective: •To further evaluate efficacy of a single infusion of PF-06838435 (fidanacogene elaparvovec) in male pediatric participants <18 years of age with moderately severe to severe hemophilia B (FIX:C=2%)<br>•Safety and tolerability of a single infusion of PF-06838435 (fidanacogene elaparvovec) in male pediatric participants <18 years of age with moderately severe to severe hemophilia B (FIX:C=2%)<br>•Assess durability of efficacy up to 5 years;Primary end point(s): •ABR for the first year post-PF-06838435 infusion versus ABR for prophylaxis FIX replacement regimen (retrospectively collected during the 1 year immediately prior to informed consent). <br>•Steady-state vector-derived FIX:C level (from Week 12 to 1 year). ;Timepoint(s) of evaluation of this end point: from Week 12 to 1 year
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •AIR for the first year post-infusion<br>Additional Secondary Endpoints:<br>•Annualized dose and total factor consumption during the first year post infusion<br>•Percentage of participants without bleeds during the first year post-infusion<br>•Change from baseline in joint health as measured by the HJHS instrument at 1 year post-infusion <br>•Change from baseline in quality of life measured by: Haem-A-QoL/Haemo-QoL Physical Health domain score at 1-year post-infusion, if age cohort appropriate<br>•Change from baseline in activity level measured by pedHAL Function of the Legs domain score at 1-year post infusion, if age cohort appropriate<br>•Incidence and severity of adverse events collected during the study;Timepoint(s) of evaluation of this end point: first year post infusion