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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

PHASE1PHASE2RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT06379789

Intervention or treatment

DRUG: REGV131

DRUG: LNP1265

Conditions

  • Hemophilia B

  • Condition: Hemophilia B

  • DRUG: REGV131 and other drugs

  • Camperdown, New South Wales, Australia

  • Sponsor: Regeneron Pharmaceuticals

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Royal Prince Alfred Hospital, Haemophilia Treatment Centre

Select from list below to view details:

  • Royal Prince Alfred Hospital, Haemophilia Treatment Centre

    Camperdown, New South Wales, Australia

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Who is running the clinical trial?

RP

Regeneron Pharmaceuticals

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
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

                What is the study measuring?

                Primary Outcome

                MeasureDescriptionTime Frame
                Incidence of treatment-emergent adverse events (TEAEs)Part 1, Part 2B and Part 2CUp to 104 Weeks
                Severity of TEAEsPart 1, Part 2B and Part 2CUp to 104 Weeks
                Coagulation Factor IX (FIX) functional activity measured using the chromogenic substrate assayPart 1At day 29
                Change in FIX functional activity in plasma, measured using the chromogenic substrate assayPart 2A, Part 2B and Part 2CBaseline 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 RDEPart 2A, Part 2B and Part 2COver 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing

                Secondary Outcome

                MeasureDescriptionTime Frame
                Change in FIX functional activity in plasma measured using the chromogenic substrate assayPart 1Baseline and at Week 26, after REGV131-LNP1265 dosing at the RDE
                ABR following sustained FIX functional activity among participants receiving the RDEPart 1Over 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 assayNot SpecifiedUp to 104 Weeks
                Annualized treated bleeding rate (tABR) following sustained FIX functional activity, among participants receiving the RDENot SpecifiedOver 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 RDENot SpecifiedOver 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing
                Remaining free of FIX replacement therapy among those receiving the RDE following sustained FIX expressionNot SpecifiedOver 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing
                Remaining zero spontaneous bleeding events among those receiving the RDE over sustained FIX functional activity periodNot SpecifiedOver 52 Weeks; Weeks 26 to 78 post-REGV131-LNP1265 dosing
                Concentrations of REGV131 componentsNot SpecifiedUp to 29 Days
                Concentrations of LNP1265 componentsNot SpecifiedUp to 29 Days
                Detection of antibodies to the F9 transgene product FIX proteinNot SpecifiedUp to 104 Weeks
                Detection of total binding antibodies (TAbs) to the adeno-associated virus 8 (AAV8) capsid proteinsNot SpecifiedUp to 104 Weeks
                Detection of neutralizing antibodies/transduction inhibitors (NAb/TI) to the adeno-associated virus 8 (AAV8) capsid proteinsNot SpecifiedUp to 104 Weeks
                Detection of antibodies to LNP1265Not SpecifiedUp to 104 Weeks
                Detection of antibodies to CRISPR-associated protein 9 (Cas9) proteinNot SpecifiedUp to 104 Weeks
                Detection of vector DNA in bloodPart 1Up to 104 Weeks
                Detection of vector DNA in salivaPart 1Up to 104 Weeks
                Detection of vector DNA in nasal secretionsPart 1Up to 104 Weeks
                Detection of vector DNA in semenPart 1Up to 104 Weeks
                Detection of vector DNA in urinePart 1Up to 104 Weeks
                Detection of vector DNA in fecesPart 1Up to 104 Weeks
                Incidence of TEAEsPart 2AUp to 104 Weeks
                Severity of TEAEsPart 2AUp to 104 Weeks
                Detection of vector DNA in relevant matrices based on data analysis of Part 1 Dose Confirmation CohortPart 2AUp to 104 Weeks
                Detection of vector DNA in relevant matrices over time based on data analysis from adult cohorts over timePart 2B and Part 2CUp to 104 Weeks
                Are you running this trial?If you're a clinic or sponsor, you can claim this study.
                Claim this trial

                References

                Clinical Trials Gov: 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

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