A Two-Part Open-Label Study of REGV131-LNP1265, A CRISPR/Cas9 Based Coagulation Factor IX Gene Insertion Therapy in Participants With Hemophilia B

Plain English Summary

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 is a Phase 2 clinical trial sponsored by Regeneron Pharmaceuticals studying Hemophilia B. This trial tests a new gene therapy called REGV131-LNP1265 to see if it's safe and effective for people with Hemophilia B. It is for individuals diagnosed with severe or moderately severe Hemophilia B. Participation involves receiving the study drug as an infusion and regular check-ups to monitor safety and effectiveness. Current treatments for Hemophilia B involve regular infusions of clotting factor; this gene therapy aims to provide a long-term solution. The trial aims to enroll 130 participants.

Official 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

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals with a confirmed diagnosis of severe or moderately severe Hemophilia B. Must have a history of low blood clotting factor levels (2% or less) or a known genetic cause for severe Hemophilia B. Must have been on regular clotting factor infusions (prophylaxis) for at least 6 months. Cannot have a history of developing inhibitors (immune system reactions) to clotting factor or specific antibodies to the gene therapy's delivery system (AAV8). This trial is studying Hemophilia B, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes will show if the gene therapy is safe by tracking side effects and if it successfully increases the body's ability to produce clotting factor, measured by Factor IX activity level The specific primary outcome measures are: Incidence of treatment-emergent adverse events (TEAEs) (Up to 104 Weeks); Severity of TEAEs (Up to 104 Weeks); Coagulation Factor IX (FIX) functional activity measured using the chromogenic substrate assay (At day 29); Change in FIX functional activity in plasma, measured using the chromogenic substrate assay (Baseline and at Week 26, after REGV131-LNP1265 dosing at the recommended dose for expansion (RDE)); Annualized bleeding rate (ABR) following sustained FIX functional activity among participants receiving the RDE (Over 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant unmet need in Hemophilia B by investigating a one-time gene therapy designed to enable the body to produce its own clotting factor, potentially eliminating the need Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Hemophilia B, where improved treatment options are needed.

Investor Insight

This trial represents a significant investment in the growing gene therapy market for rare diseases, with a high potential for success if the therapy proves safe and effective, offering a novel treatm Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of gene therapy, how it differs from your current treatment, and what the commitment involves. Participation includes receiving the study drug, attending regular clinic visits for monitoring, and potentially undergoing blood tests and health assessments. Be prepared for potential travel to study sites and a commitment to the study duration, which includes follow-up periods. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 130 participants

Interventions

• DRUG: REGV131 — Single dose administered via intravenous (IV) infusion before LNP1265
• DRUG: LNP1265 — Single dose administered via IV infusion following REGV131

Primary Outcomes

• Incidence of treatment-emergent adverse events (TEAEs) (Up to 104 Weeks)
• Severity of TEAEs (Up to 104 Weeks)
• Coagulation Factor IX (FIX) functional activity measured using the chromogenic substrate assay (At day 29)
• Change in FIX functional activity in plasma, measured using the chromogenic substrate assay (Baseline and at Week 26, after REGV131-LNP1265 dosing at the recommended dose for expansion (RDE))
• Annualized bleeding rate (ABR) following sustained FIX functional activity among participants receiving the RDE (Over 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing)

Secondary Outcomes

• Change in FIX functional activity in plasma measured using the chromogenic substrate assay (Baseline and at Week 26, after REGV131-LNP1265 dosing at the RDE)
• ABR following sustained FIX functional activity among participants receiving the RDE (Over 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing)
• FIX functional activity in plasma over time during the study period using the chromogenic substrate assay (Up to 104 Weeks)
• Annualized treated bleeding rate (tABR) following sustained FIX functional activity, among participants receiving the RDE (Over 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing)
• Annualized utilization (IU/kg/year) of FIX replacement therapy following sustained FIX functional activity among participants receiving the RDE (Over 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing)

Full 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

Trial Locations

• Orthopaedic Hemophilia Treatment Center, Los Angeles, California, United States
• David Geffen School of Medicine at UCLA, Los Angeles, California, United States
• Children's Hospital Los Angeles, Los Angeles, California, United States
• University of California Davis, Sacramento, California, United States
• University California San Francisco, San Francisco, California, United States
• University of Colorado Hemophilia and Thrombosis Center, Aurora, Colorado, United States
• Yale HTC, New Haven, Connecticut, United States
• University of Florida, Gainesville, Florida, United States
• Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, United States
• Tulane University School of Medicine, Louisiana Center for Bleeding and Clotting Disorders, New Orleans, Louisiana, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Hemophilia B
• Bleeding Disorders
• Genetic Disorders
• Hematology
• Rare Diseases
• Gene Therapy
• Coagulation Disorders
• Factor IX Deficiency
• Orthopedics (due to joint bleeds)
• Immunology

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