A Study to Investigate the Safety and Effectiveness of a Coagulation Factor IX Gene Insertion Therapy (REGV131-LNP1265) in Pediatric, Adolescent and Adult Participants With Hemophilia B

The study will be conducted with a 2-part adaptive design, with enrollment of patients into sequential parts of the study.

Part 1: Dose Escalation and Dose Confirmation in adult patients ≥18 years of age

• Dose Escalation Cohorts to determine the Recommended Dose for Expansion (RDE) of REGV131-LNP1265
• Dose Confirmation Cohort to gain further confidence in safety, tolerability, and Coagulation Factor IX (FIX) functional activity data at the RDE

Part 2: Dose Expansion at the RDE

• Part 2A: Adult patients ≥18 years of age: RDE of REGV131-LNP1265, as determined in Part 1
• Part 2B: Adolescent patients ≥12 to <18 years of age will be administered weight-adjusted RDE
• Part 2C: Adolescent and Pediatric patients ≥2 to <12 years may be enrolled in an age staggered sequential manner; first participants aged ≥6 to <12 years and then participants ≥2 to <6 years of age and will receive a weight-adjusted RDE

Key Inclusion Criteria:

• Confirmed diagnosis of severe or moderately severe hemophilia B with medical history of FIX functional activity (≤2% or <0.02 IU/mL) or documented genotype known to produce severe hemophilia B
• Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol
• Participation in the lead-in period of this interventional study OR a separate lead-in study (R0000-HEMB-2187 [NCT05568459]) for at least 6 months for ABR data while taking FIX prophylaxis, as defined in the protocol

Key Exclusion Criteria:

• History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions
• Bethesda inhibitor titer greater than the Upper Limit of Normal (ULN) at screening
• Detectable pre-existing antibodies to the AAV8 capsid; as measured by Enzyme-Linked ImmunoSorbent Assay (ELISA) at prescreening (or final lead-in visit, if applicable)
• Any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy
• Evidence of advanced liver fibrosis or significant fatty liver, as defined in the protocol
• Evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit
• History of arterial or venous thrombo-embolic events, as defined in the protocol
• History of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids
• Previously received any AAV gene-based therapy or intends to receive approved or investigational AAV-based gene therapy other than REGV131-LNP1265 during the study period

NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply