CClinicalTrials.gg
Sign In
RecruitingNCT06379789BEYOND-9Updated Sep 11, 2026

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

A Phase 1/2 interventional study of REGV131 and LNP1265 in Hemophilia B, sponsored by Regeneron Pharmaceuticals. Recruiting at 49 sites in 9 countries. Open to male participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2026-09-11.

Sponsored by Regeneron Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
130
Allocation
Non-randomized
Ages
2 Years and older
Sex
Male
01

Study 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
Read the detailed description

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
02

Conditions studied

  • Hemophilia B

Browse trials for

Keywords

  • Severe and moderately severe congenital hemophilia B
  • FIX functional activity
03

Who can participate

Ages eligible
2 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

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 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 or significant fatty liver, 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

04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
130 participants (estimated)

Study arms

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    Part 2: Dose Expansion A

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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

  • Experimental
    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

    Drug: REGV131 · Drug: LNP1265

Interventions

  • DrugREGV131

    Administered per the protocol before LNP1265

  • DrugLNP1265

    Administered per the protocol following REGV131

05

What researchers measure

Primary outcomes

  1. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Part 1, 2B, and 2C

    Time frame: Up to 2 Years

  2. Severity of TEAEs

    Part 1, 2B, and 2C

    Time frame: Up to 2 Years

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

    Part 1

    Time frame: Up to 2 Years

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

    Part 2A, 2B, and 2C

    Time frame: Up to 2 Years

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

    Part 2A, 2B, and 2C

    Time frame: Up to 2 Years

  6. Occurrence of Serious Adverse Events (SAEs)

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

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

  7. Severity of SAEs

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

    Time frame: Through LTFU, Up to 15 Years

  8. Occurrence of Adverse Event of Special Interests (AESIs)

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

    Time frame: Through LTFU, Up to 15 Years

  9. Severity of AESIs

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

    Time frame: Through LTFU, Up to 15 Years

  10. Occurrence of clinically meaningful Adverse Events (AEs)

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

    Time frame: Through LTFU, Up to 15 Years

  11. Severity of clinically meaningful AEs

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

    Time frame: Through LTFU, Up to 15 Years

Secondary outcomes

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

    Part 1

    Time frame: Up to 2 Years

  2. ABR following sustained FIX functional activity among participants receiving the RDE

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

    Time frame: Through LTFU, Up to 15 Years

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

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

    Time frame: Through LTFU, Up to 10 Years

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

    Part 1, 2A, 2B, and 2C

    Time frame: Through LTFU, Up to 15 years

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

    Part 1, 2A, 2B, and 2C

    Time frame: Through LTFU, Up to 15 Years

  6. Remaining free of FIX replacement therapy among those receiving the RDE following sustained FIX expression

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  7. Remaining zero spontaneous bleeding events among those receiving the RDE over sustained FIX functional activity period

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  8. Concentrations of REGV131 components

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  9. Concentrations of LNP1265 components

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  10. Detection of antibodies to the Coagulation Factor IX gene (F9) transgene product FIX protein

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  11. Detection of Total binding Antibodies (TAbs) to the Adeno-Associated Virus 8 (AAV8) capsid proteins

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  12. Detection of Neutralizing Antibodies/Transduction Inhibitors (NAb/TI) to the AAV8 capsid proteins

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  13. Detection of antibodies to LNP1265

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  14. Detection of antibodies to CRISPR-associated protein 9 (Cas9) protein

    Part 1, 2A, 2B, and 2C

    Time frame: Up to 2 Years

  15. Detection of vector DeoxyriboNucleic Acid (DNA) in blood

    Part 1

    Time frame: Up to 2 Years

  16. Detection of vector DNA in saliva

    Part 1

    Time frame: Up to 2 Years

  17. Detection of vector DNA in nasal secretions

    Part 1

    Time frame: Up to 2 Years

  18. Detection of vector DNA in semen

    Part 1

    Time frame: Up to 2 Years

  19. Detection of vector DNA in urine

    Part 1

    Time frame: Up to 2 Years

  20. Detection of vector DNA in feces

    Part 1

    Time frame: Up to 2 Years

  21. Occurrence of TEAEs

    Part 2A

    Time frame: Up to 2 Years

  22. Severity of TEAEs

    Part 2A

    Time frame: Up to 2 Years

  23. Detection of vector DNA in relevant matrices based on data analysis of Part 1 Dose Confirmation Cohort

    Part 2A, 2B, and 2C

    Time frame: Up to 2 Years

  24. Detection of vector DNA in relevant matrices over time based on data analysis from adult cohorts over time

    Part 2B and 2C

    Time frame: Up to 2 Years

  25. Proportion of participants with zero spontaneous bleeding events following sustained FIX functional activity among those receiving RDE

    Part 1, 2A, 2B, and 2C

    Time frame: Through LTFU, Up to 15 Years

  26. Proportion of participants not requiring FIX replacement therapy following sustained FIX functional activity among those receiving RDE

    Part 1, 2A, 2B, and 2C

    Time frame: Throught LTFU, Up to 15 Years

06

Study locations

49 of 49 sites recruiting
  • 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
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
    Recruiting
  • University of Texas Health Science Center at Houston
    Houston, Texas 77030, United States
    Recruiting
  • Royal Prince Alfred Hospital, Haemophilia Treatment Centre
    Camperdown, New South Wales 2050, Australia
    Recruiting
  • Royal Brisbane and Women's Hospital
    Herston, Queensland 4029, Australia
    Recruiting
  • Royal Adelaide Hospital
    Adelaide, South Australia 5000, Australia
    Recruiting
  • Alfred Hospital
    Melbourne, Victoria 3004, Australia
    Recruiting
  • Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos
    Vitória, Espírito Santo 29047-105, Brazil
    Recruiting
  • Hemocentro Unicamp
    Campinas, São Paulo 13084-878, Brazil
    Recruiting
  • Hemorio
    Rio de Janeiro, 20211030, Brazil
    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
07

References and documents

Individual participant data

Plan to share: Yes — All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

08

Registry details

Key details

Study ID
NCT06379789
Lead sponsor
Regeneron Pharmaceuticals
Collaborators
Intellia Therapeutics
Responsible party
Sponsor
First posted
Apr 23, 2024
Start date
Sep 11, 2024
Primary completion
Aug 14, 2034 (estimated)
Completion
Aug 14, 2047 (estimated)
Last update
Sep 11, 2026

Study contacts

Clinical Trials Administrator
Contact
clinicaltrials@regeneron.com
844-734-6643
Clinical Trial Management
study director · Regeneron Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Hemophilia B→

Other studies from this sponsor

Regeneron Pharmaceuticals

Start the discussion