A Trial to Learn if REGV131-LNP1265 is Safe and Works to Help the Body Make Clotting Factor in Adult Patients with Hemophilia B

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

16 Jun 2025 → ongoing

Decision date (initial)

2024-09-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Part 1: To evaluate the safety and tolerability of a single IV administration of REGV131-LNP1265 in participants with hemophilia B.
To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B to establish the recommended dose for further development
Part 2A: To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B receiving the recommended dose for expansion (RDE).
To assess the bleeding event rate (all bleeding events) following a single IV administration of REGV131-LNP1265 at the RDE

Secondary objectives 12

1. Part 1: To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B receiving the RDE.
2. Part 1: To assess the bleeding event rate (all bleeding events) following a single IV administration of REGV131-LNP1265 at the RDE.
3. Part 1: To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B
4. Part 1: To assess the bleeding event rate for bleeding events that require treatment with FIX replacement therapy following a single IV administration of REGV131-LNP1265 at the RDE.
5. Part 1: To evaluate FIX replacement therapy use following a single IV administration of REGV131-LNP1265 at the RDE, excluding FIX replacement for invasive procedures
6. Part 2A: To evaluate the safety and tolerability of a single IV administration of REGV131-LNP1265 in participants with hemophilia B.
7. Part 2A: To evaluate clotting FIX functional activity following a single IV administration of REGV131-LNP1265 in participants with hemophilia B.
8. Part 2A: To assess the bleeding event rate for bleeding events that require treatment with FIX replacement therapy following a single IV administration of REGV131-LNP1265 at the RDE.
9. Part 2A: To evaluate FIX replacement therapy use following a single IV administration of REGV131-LNP1265 at the RDE, excluding FIX replacement for invasive procedures
10. Parts 1 and 2A: To characterize the concentration-time profile of REGV131-LNP1265
11. Parts 1 and 2A: To assess humoral immunogenicity of REGV131- LNP1265 following a single IV administration.
12. Parts 1 and 2A: To assess vector shedding after a single IV administration of REGV131-LNP1265.

Conditions and MedDRA coding

Hemophilia B

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, The Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male gender at birth and ≥18 years of age.
2. 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.
3. Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol.
4. 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.
5. NOTE: Other Inclusion Protocol Defined Criteria Apply.

Exclusion criteria 10

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 [L-Final], 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.
10. NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Incidence and severity of treatment-emergent adverse events (TEAEs) up to 104 weeks.
2. Part 1: Coagulation Factor IX (FIX) functional activity at day 29 measured using the chromogenic substrate assay.
3. Part 2A: Change from baseline in FIX functional activity in plasma at week 26 after REGN131-LNP1265 dosing at the recommended dose for expansion (RDE) measured using the chromogenic substrate assay.
4. Part 2A: Annualized bleeding rate (ABR) over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving RDE.

Secondary endpoints 17

1. Part 1: Change from baseline in FIX functional activity in plasma at 26 weeks after REGV131-LNP1265 dosing at the RDE, measured using the chromogenic substrate assay.
2. Part 1: ABR over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.
3. Part 1 and Part 2A: FIX functional activity in plasma over time during the study period using the chromogenic substrate assay up to 104 weeks.
4. Part 1 and Part 2A: Annualized treated bleeding rate (tABR) over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.
5. Part 1 and Part 2A: Annualized utilization (IU/kg/year) of FIX replacement therapy over 52 weeks following sustained FIX functional activity (weeks 26-78 post-REGV131-LNP1265 dosing) among participants receiving the RDE.
6. Part 1 and Part 2A: Remaining free of FIX replacement therapy among those receiving the RDE over 52 weeks following sustained FIX expression (weeks 26-78 post-REGV131-LNP1265 dosing).
7. Part 1 and Part 2A: Remaining zero spontaneous bleeding events among those receiving the RDE over the 52 weeks of sustained FIX functional activity period (weeks 26-78 post-REGV131-LNP1265 dosing).
8. Part 1 and Part 2A: Concentrations of REGV131 components up to 29 days.
9. Part 1 and Part 2A: Concentrations of LNP1265 components up to 29 days.
10. Part 1 and Part 2A: Detection of antibodies to the F9 transgene product FIX protein up to 104 weeks.
11. Part 1 and Part 2A: Detection of total binding antibodies (TAbs) to the adeno-associated virus 8 (AAV8) capsid proteins up to 104 weeks.
12. Part 1 and Part 2A: Detection of neutralizing antibodies/transduction inhibitors (NAb/TI) to the adeno-associated virus 8 (AAV8) capsid proteins up to 104 weeks.
13. Part 1 and Part 2A: Detection of antibodies to LNP1265 up to 104 weeks.
14. Part 1 and Part 2A: Detection of antibodies to CRISPR-associated protein 9 (Cas9) protein up to 104 weeks.
15. Part 1: Detection of vector DNA in blood, saliva, nasal secretions, semen, urine, and feces over time (Part 1 dose confirmation cohort only)
16. Part 2A: Incidence and severity of TEAEs up to 104 weeks.
17. Part 2A: Detection of vector DNA in relevant matrices based on data analysis of Part 1 Dose Confirmation Cohort up to 104 weeks.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 12

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 82 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications