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

NCT06379789 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: R131L1265-HEMB-23182023-507260-40-00
• Study Type: interventional
• Target: 130
• Locations: 8 countries
• Sites: 41

Brief 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, both in the near term and over time. 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 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

Conditions

Hemophilia B

Keywords

Severe and moderately severe congenital hemophilia B; FIX functional activity

Outcome Measures

Primary Outcomes (11)

• Occurrence of Treatment-Emergent Adverse Events (TEAEs)

  Part 1, 2B, and 2C

  Up to 2 Years

• Severity of TEAEs

  Part 1, 2B, and 2C

  Up to 2 Years

• Coagulation Factor IX (FIX) functional activity measured using the chromogenic substrate assay

  Part 1

  Up to 2 Years

• Change in FIX functional activity in plasma, measured using the chromogenic substrate assay

  Part 2A, 2B, and 2C

  Up to 2 Years

• Annualized Bleeding Rate (ABR) following sustained FIX functional activity among participants receiving the RDE

  Part 2A, 2B, and 2C

  Up to 2 Years

• Occurrence of Serious Adverse Events (SAEs)

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through Long Term Follow Up (LTFU), Up to 15 Years

• Severity of SAEs

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through LTFU, Up to 15 Years

• Occurrence of Adverse Event of Special Interests (AESIs)

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through LTFU, Up to 15 Years

• Severity of AESIs

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through LTFU, Up to 15 Years

• Occurrence of clinically meaningful Adverse Events (AEs)

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through LTFU, Up to 15 Years

• Severity of clinically meaningful AEs

  LTFU Period for Part 1, 2A, 2B, and 2C

  Through LTFU, Up to 15 Years

Secondary Outcomes (26)

• Change in FIX functional activity in plasma measured using the chromogenic substrate assay

  Up to 2 Years

• ABR following sustained FIX functional activity among participants receiving the RDE

  Through LTFU, Up to 15 Years

• FIX functional activity in plasma over time during the study period using the chromogenic substrate assay

  Through LTFU, Up to 10 Years

• Annualized treated Bleeding Rate (tABR) following sustained FIX functional activity, among participants receiving the RDE

  Through LTFU, Up to 15 years

• Annualized utilization (IU/kg/year) of FIX replacement therapy following sustained FIX functional activity among participants receiving the RDE

  Through LTFU, Up to 15 Years

Study Arms (7)

Part 1: Cohort 1 Dose Escalation for RDE

EXPERIMENTAL

Starting dose to determine the RDE of REGV131-LNP1265 and further assess the safety, tolerability, and FIX functional activity data at the RDE

Drug: REGV131; Drug: LNP1265

Part 1: Cohort 2 Dose Escalation for RDE

EXPERIMENTAL

Dose 2 of ascending dose level cohorts to determine the RDE of REGV131-LNP1265 and further assess the safety, tolerability, and FIX functional activity data at the RDE

Drug: REGV131; Drug: LNP1265

Part 1: Cohort 3 Dose Escalation for RDE

EXPERIMENTAL

Dose 3 of ascending dose level cohorts to determine the RDE of REGV131-LNP1265 and further assess the safety, tolerability, and FIX functional activity data at the RDE

Drug: REGV131; Drug: LNP1265

Part 1: Cohort 4 Dose Escalation for RDE

EXPERIMENTAL

Dose 4 of ascending dose level cohorts to determine the RDE of REGV131-LNP1265 and further assess the safety, tolerability, and FIX functional activity data at the RDE

Drug: REGV131; Drug: LNP1265

Part 2: Dose Expansion A

EXPERIMENTAL

Participants ≥18 Years of Age will receive the RDE of REGV131-LNP1265 determined by Part 1

Drug: REGV131; Drug: LNP1265

Part 2: Dose Expansion B

EXPERIMENTAL

Participants ≥12 to \<18 Years of Age will receive the administered weight-adjusted RDE of REGV131-LNP1265 determined by Part 1

Drug: REGV131; Drug: LNP1265

Part 2: Dose Expansion C

EXPERIMENTAL

Participants ≥2 to \<12 Years of Age will receive the administered weight-adjusted RDE of REGV131-LNP1265 determined by Part 1

Drug: REGV131; Drug: LNP1265

Interventions

REGV131 DRUG

Administered per the protocol before LNP1265

Part 1: Cohort 1 Dose Escalation for RDE; Part 1: Cohort 2 Dose Escalation for RDE; Part 1: Cohort 3 Dose Escalation for RDE; Part 1: Cohort 4 Dose Escalation for RDE; Part 2: Dose Expansion A; Part 2: Dose Expansion B; Part 2: Dose Expansion C

LNP1265 DRUG

Administered per the protocol following REGV131

Part 1: Cohort 1 Dose Escalation for RDE; Part 1: Cohort 2 Dose Escalation for RDE; Part 1: Cohort 3 Dose Escalation for RDE; Part 1: Cohort 4 Dose Escalation for RDE; Part 2: Dose Expansion A; Part 2: Dose Expansion B; Part 2: Dose Expansion C

Eligibility Criteria

• Age: 2 Years+
• Gender Eligibility Details: Male gender at birth: Part 1: \> 18 years of age, irrespective of weight Part 2A: \> 18 years of age, irrespective of weight Part 2B: ≥12 to \<18 years of age with weight ≥45 kg Part 2C: ≥ 2 to \< 12 years of age
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Intellia Therapeutics: collaborator

Study Sites (41)

Orthopaedic Hemophilia Treatment Center

Los Angeles, California, 90007, United States

RECRUITING

David Geffen School of Medicine at UCLA

Los Angeles, California, 90024, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

University of California Davis

Sacramento, California, 95817, United States

RECRUITING

University California San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

RECRUITING

Yale HTC

New Haven, Connecticut, 06510, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

RECRUITING

Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders

New Orleans, Louisiana, 70112, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Royal Prince Alfred Hospital, Haemophilia Treatment Centre

Camperdown, New South Wales, 2050, Australia

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

McGill University Health Center (MUHC)

Montreal, Quebec, H4J 3A1, Canada

RECRUITING

Hospices Civils de Lyon

Bron, Lyon, 69677, France

RECRUITING

Hemostase Clinique, Institut Coeur Poumon

Lille, Nord, 59037, France

RECRUITING

Hopital Necker

Paris, Île-de-France Region, 75015, France

RECRUITING

University Hospital Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

University Hospital Hamburg Eppendorf

Hamburg, 20246, Germany

RECRUITING

Careggi University Hospital

Florence, Firenze, 50134, Italy

RECRUITING

Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

RECRUITING

Irccs Humanitas Research Hospital

Rozzano, Lombardy, 20089, Italy

RECRUITING

Ospedale san Bortolo

Vicenza, 36100, Italy

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

RECRUITING

Complejo Hospitalario Universitario de A Coruña (Edificio Teresa Herrera-Materno Infantil)

A Coruña, Galicia, 15006, Spain

RECRUITING

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Haemostasis and Thrombosis Unit, Hospital La Fe

Valencia, 46026, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

Glasgow Royal Infirmary - Clinical Research Facility

Glasgow, Scotland, G31 2ER, United Kingdom

RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Addenbrooke's Hospital, Cambridge University Hospitals NHS FT

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Pathology and Pharmacy Building, The Royal London Hospital

London, E1 2ES, United Kingdom

RECRUITING

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

RECRUITING

St. Thomas' Hospital

London, SE1 7EH, United Kingdom

RECRUITING

Hammersmith Hospital Comprehensive Care Centre

London, W12 0HS, United Kingdom

RECRUITING

Related Links

• Study Information Website

MeSH Terms

Conditions

Hemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 23, 2024
• Study Start: September 11, 2024
• Primary Completion (Estimated): August 14, 2034
• Study Completion (Estimated): August 14, 2047
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

CA (3); FR (3); US (13); DE (2); IT (4); AU (1); GB (7); ES (8)