Hemophilia BPhase 1/2BEYOND-9NCT06379789
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 study testing REGV131 and LNP1265 in people with Hemophilia B, run by Regeneron Pharmaceuticals at 52 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 years and older, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- REGV131 and LNP1265
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 52 sitesin 9 countries
- Study dates
- 11 Sep 2024to 14 Aug 2047
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
52 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
52 sites in 9 countries
United States17 sites, 17 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
University of Colorado Hemophilia and Thrombosis Center
Aurora, Colorado, 80045
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
- Recruiting
Children's Medical Center Dallas
Dallas, Texas, 75235
- Recruiting
University of Florida
Gainesville, Florida, 32610
- Recruiting
University of Texas Health Science Center at Houston
Houston, Texas, 77030
- Recruiting
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
- Recruiting
Orthopaedic Hemophilia Treatment Center
Los Angeles, California, 90007
- Recruiting
David Geffen School of Medicine at UCLA
Los Angeles, California, 90024
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Yale HTC
New Haven, Connecticut, 06510
- Recruiting
Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders
New Orleans, Louisiana, 70112
- Recruiting
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
- Recruiting
Phoenix Children's Hospital
Phoenix, Arizona, 85016
- Recruiting
University of California Davis
Sacramento, California, 95817
- Recruiting
University California San Francisco
San Francisco, California, 94143
Spain8 sites, 8 recruiting
- Recruiting
Complejo Hospitalario Universitario de A Coruña (Edificio Teresa Herrera-Materno Infantil)
A Coruña, Galicia, 15006
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
- Recruiting
Hospital Clinico Universitario Virgen De La Arrixaca
El Palmar, Murcia, 30120
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
- Recruiting
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, Andalusia, 41013
- Recruiting
Haemostasis and Thrombosis Unit, Hospital La Fe
Valencia, 46026
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
United Kingdom8 sites, 8 recruiting
- Recruiting
Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2TH
- Recruiting
Addenbrooke's Hospital, Cambridge University Hospitals NHS FT
Cambridge, CB2 0QQ
- Recruiting
Glasgow Royal Infirmary - Clinical Research Facility
Glasgow, Scotland, G31 2ER
- Recruiting
Pathology and Pharmacy Building, The Royal London Hospital
London, E1 2ES
- Recruiting
Royal Free London NHS Foundation Trust
London, NW3 2QG
- Recruiting
St. Thomas' Hospital
London, SE1 7EH
- Recruiting
Hammersmith Hospital Comprehensive Care Centre
London, W12 0HS
- Recruiting
Oxford Haemophilia and Thrombosis Centre (OHTC)
Oxford, Oxfordshire, OX3 7HE
Australia4 sites, 4 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
- Recruiting
Royal Prince Alfred Hospital, Haemophilia Treatment Centre
Camperdown, New South Wales, 2050
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
- Recruiting
Alfred Hospital
Melbourne, Victoria, 3004
Italy4 sites, 4 recruiting
- Recruiting
Careggi University Hospital
Florence, Firenze, 50134
- Recruiting
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
- Recruiting
Irccs Humanitas Research Hospital
Rozzano, Lombardy, 20089
- Recruiting
Ospedale san Bortolo
Vicenza, 36100
Brazil3 sites, 3 recruiting
- Recruiting
Hemocentro Unicamp
Campinas, São Paulo, 13084-878
- Recruiting
Hemorio
Rio de Janeiro, 20211030
- Recruiting
Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos
Vitória, Espírito Santo, 29047-105
Canada3 sites, 3 recruiting
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
- Recruiting
McMaster University Medical Centre - Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
- Recruiting
McGill University Health Center (MUHC)
Montreal, Quebec, H4J 3A1
France3 sites, 3 recruiting
- Recruiting
Hospices Civils de Lyon
Bron, Lyon, 69677
- Recruiting
Hemostase Clinique, Institut Coeur Poumon
Lille, Nord, 59037
- Recruiting
Hopital Necker
Paris, Île-de-France Region, 75015
Germany2 sites, 2 recruiting
- Recruiting
University Hospital Frankfurt
Frankfurt am Main, Hesse, 60590
- Recruiting
University Hospital Hamburg Eppendorf
Hamburg, 20246
About this study
Official title: A Two-Part Open-Label Study of REGV131-LNP1265, A CRISPR/Cas9 Based Coagulation Factor IX Gene Insertion Therapy in Participants With Hemophilia B
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.
Read more
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
- Conditions
- Hemophilia B
- Being tested
- REGV131, LNP1265
- Keywords
- Severe and moderately severe congenital hemophilia B, FIX functional activity
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGV131Drug
Administered per the protocol before LNP1265
LNP1265Drug
Administered per the protocol following REGV131
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: REGV131; Drug: LNP1265 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Part 1, 2B, and 2C
Measured: Up to 2 Years
Severity of TEAEs
Part 1, 2B, and 2C
Measured: Up to 2 Years
Coagulation Factor IX (FIX) functional activity measured using the chromogenic substrate assay
Part 1
Measured: Up to 2 Years
Change in FIX functional activity in plasma, measured using the chromogenic substrate assay
Part 2A, 2B, and 2C
Measured: Up to 2 Years
Annualized Bleeding Rate (ABR) following sustained FIX functional activity among participants receiving the RDE
Part 2A, 2B, and 2C
Measured: Up to 2 Years
Occurrence of Serious Adverse Events (SAEs)
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through Long Term Follow Up (LTFU), Up to 15 Years
Severity of SAEs
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Occurrence of Adverse Event of Special Interests (AESIs)
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Severity of AESIs
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Occurrence of clinically meaningful Adverse Events (AEs)
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Severity of clinically meaningful AEs
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Secondary outcomes (26)
Change in FIX functional activity in plasma measured using the chromogenic substrate assay
Part 1
Measured: Up to 2 Years
ABR following sustained FIX functional activity among participants receiving the RDE
LTFU Period for Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
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
Measured: Through LTFU, Up to 10 Years
Annualized treated Bleeding Rate (tABR) following sustained FIX functional activity, among participants receiving the RDE
Part 1, 2A, 2B, and 2C
Measured: 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
Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Remaining free of FIX replacement therapy among those receiving the RDE following sustained FIX expression
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Remaining zero spontaneous bleeding events among those receiving the RDE over sustained FIX functional activity period
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Concentrations of REGV131 components
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Concentrations of LNP1265 components
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of antibodies to the Coagulation Factor IX gene (F9) transgene product FIX protein
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of Total binding Antibodies (TAbs) to the Adeno-Associated Virus 8 (AAV8) capsid proteins
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of Neutralizing Antibodies/Transduction Inhibitors (NAb/TI) to the AAV8 capsid proteins
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of antibodies to LNP1265
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of antibodies to CRISPR-associated protein 9 (Cas9) protein
Part 1, 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of vector DeoxyriboNucleic Acid (DNA) in blood
Part 1
Measured: Up to 2 Years
Detection of vector DNA in saliva
Part 1
Measured: Up to 2 Years
Detection of vector DNA in nasal secretions
Part 1
Measured: Up to 2 Years
Detection of vector DNA in semen
Part 1
Measured: Up to 2 Years
Detection of vector DNA in urine
Part 1
Measured: Up to 2 Years
Detection of vector DNA in feces
Part 1
Measured: Up to 2 Years
Occurrence of TEAEs
Part 2A
Measured: Up to 2 Years
Severity of TEAEs
Part 2A
Measured: Up to 2 Years
Detection of vector DNA in relevant matrices based on data analysis of Part 1 Dose Confirmation Cohort
Part 2A, 2B, and 2C
Measured: Up to 2 Years
Detection of vector DNA in relevant matrices over time based on data analysis from adult cohorts over time
Part 2B and 2C
Measured: Up to 2 Years
Proportion of participants with zero spontaneous bleeding events following sustained FIX functional activity among those receiving RDE
Part 1, 2A, 2B, and 2C
Measured: Through LTFU, Up to 15 Years
Proportion of participants not requiring FIX replacement therapy following sustained FIX functional activity among those receiving RDE
Part 1, 2A, 2B, and 2C
Measured: Throught LTFU, Up to 15 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start11 Sep 2024
- Primary completion14 Aug 2034 (estimated)
- Study completion14 Aug 2047 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Intellia Therapeutics
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06379789
- Sponsor's protocol ID
- R131L1265-HEMB-2318
- Other IDs
- 2023-507260-40-00, 2023
- Acronym
- BEYOND-9
- Status last verified
- Oct 2026
- First submitted
- 18 Apr 2024
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.