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

Conditions: Hemophilia B

Summary: participants in this study have a genetic mutation, specifically in the coagulation (blood clotting) factor 9 gene that causes severe or moderately severe hemophilia b. this study is researching an experimental gene insertion therapy (the adding of a gene into your dna) called regv131-lnp1265, also called the "study drug". gene insertion therapy aims to teach the body how to produce clotting factor long-term, without the need for factor replacement therapy. the main aim of this study is to find a safe and well-tolerated dose of the study drug by checking the side effects that may happen from taking it. the study is looking at several other research questions including: * how much study drug is in the blood at different times * whether the body makes antibodies against parts of the study drug, which could make the drug less effective or could lead to side effects. antibodies are proteins produced by the body's immune system in response to a foreign substance * whether the body makes antibodies against the clotting factor replacement therapy * how quality of life is affected by hemophilia b and if it changes after taking study drug * how joint health is affected by hemophilia b and if it changes after taking study drug * how often visits are required for the emergency room, urgent care center, physician's office, hospital, telephone or online are required as a result of bleeding events, and if the frequency changes after taking study drug * how often factor replacement therapy is needed, both on a regular basis for prevention of bleeding, and as needed to treat bleeding events (and it if changes after taking study drug) * whether there is a difference in 2 different methods for measuring factor 9 activity in the blood

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 \<18 and ≥12 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

Eligibility criteria:
key inclusion criteria: 1. 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 2. currently taking fix prophylaxis and previous experience with fix therapy, as defined in the protocol 3. 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: 1. history of fix inhibitor (clinical or laboratory-based assessment) on 2 or more occasions 2. bethesda inhibitor titer greater than the upper limit of normal (uln) at screening 3. detectable pre-existing antibodies to the adeno-associated virus serotype 8 (aav8) capsid; as measured by enzyme-linked immunosorbent assay (elisa) at prescreening (or final lead-in visit, if applicable). 4. any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy 5. evidence of advanced liver fibrosis, as defined in the protocol 6. evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit 7. history of arterial or venous thrombo-embolic events, as defined in the protocol 8. history of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids 9. 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

Keywords: severe and moderately severe congenital hemophilia b fix functional activity