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

NCT ID: NCT06379789

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-11

Study Completion Date

2032-12-17

Brief Summary

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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

Detailed Description

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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

Conditions

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Hemophilia B

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: Cohort 1 Dose Escalation for RDE

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 1: Cohort 2 Dose Escalation for RDE

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 1: Cohort 3 Dose Escalation for RDE

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 1: Cohort 4 Dose Escalation for RDE

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 2: Dose Expansion A

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 2: Dose Expansion B

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Part 2: Dose Expansion C

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

Group Type EXPERIMENTAL

REGV131

Intervention Type DRUG

Single dose administered via intravenous (IV) infusion before LNP1265

LNP1265

Intervention Type DRUG

Single dose administered via IV infusion following REGV131

Interventions

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REGV131

Single dose administered via intravenous (IV) infusion before LNP1265

Intervention Type DRUG

LNP1265

Single dose administered via IV infusion following REGV131

Intervention Type DRUG

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Intellia Therapeutics

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Orthopaedic Hemophilia Treatment Center

Los Angeles, California, United States

Site Status RECRUITING

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

University of California Davis

Sacramento, California, United States

Site Status RECRUITING

University California San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, United States

Site Status RECRUITING

Yale HTC

New Haven, Connecticut, United States

Site Status RECRUITING

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

Site Status RECRUITING

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

New Orleans, Louisiana, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Royal Prince Alfred Hospital, Haemophilia Treatment Centre

Camperdown, New South Wales, Australia

Site Status RECRUITING

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status RECRUITING

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status RECRUITING

McGill University Health Center (MUHC)

Montreal, Quebec, Canada

Site Status RECRUITING

Hospices Civils de Lyon

Bron, Lyon, France

Site Status RECRUITING

Hopital Necker

Paris, Île-de-France Region, France

Site Status RECRUITING

University Hospital Frankfurt

Frankfurt am Main, Hesse, Germany

Site Status RECRUITING

University Hospital Hamburg Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Andalusia, Spain

Site Status RECRUITING

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

A Coruña, Galicia, Spain

Site Status RECRUITING

Hospital Clinico Universitario Virgen De La Arrixaca

El Palmar, Murcia, Spain

Site Status RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Haemostasis and Thrombosis Unit, Hospital La Fe

Valencia, , Spain

Site Status RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status RECRUITING

Glasgow Royal Infirmary - Clinical Research Facility

Glasgow, Scotland, United Kingdom

Site Status RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Addenbrooke's Hospital, Cambridge University Hospitals NHS FT

Cambridge, , United Kingdom

Site Status RECRUITING

Pathology and Pharmacy Building, The Royal London Hospital

London, , United Kingdom

Site Status RECRUITING

Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

St. Thomas' Hospital

London, , United Kingdom

Site Status RECRUITING

Hammersmith Hospital Comprehensive Care Centre

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada France Germany Spain United Kingdom

Central Contacts

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Clinical Trials Administrator

Role: CONTACT

844-734-6643

Related Links

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https://hemophilia-beyond-9.com/

Study Information Website

Other Identifiers

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2023-507260-40-00

Identifier Type: CTIS

Identifier Source: secondary_id

R131L1265-HEMB-2318

Identifier Type: -

Identifier Source: org_study_id

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