A Study to Evaluate how Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) whose Current Treatment is not Working Efficiently

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2025-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-519709-37-00

ClinicalTrials.gov

NCT07154745

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the study is to evaluate the effect of pozelimab + cemdisiran combination treatment on intravascular hemolysis (IVH) in participants with inadequate control of IVH on a currently available C5i treatment.

Secondary objectives 8

1. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment on additional measures of intravascular hemolysis.
2. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment on transfusion parameters.
3. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment on hemoglobin levels.
4. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment on fatigue as assessed by clinical outcome assessments (COAs).
5. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment and to evaluate the effect of the combination treatment on the inhibition of total complement hemolytic activity (CH50).
6. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment on safety and tolerability.
7. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment by assessing the immunogenicity of pozelimab and cemdisiran.
8. The secondary efficacy objective of this study is to evaluate the effect of pozelimab + cemdisiran combination treatment in participants with inadequate control of IVH on a currently available C5i treatment by assessing the concentrations of total pozelimab in serum, and concentrations of total C5, and cemdisiran in plasma.

Conditions and MedDRA coding

Paroxysmal nocturnal hemoglobinuria (PNH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing.
2. Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months.
3. LDH persistently > 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis.
4. At least 2 screening LDH values from different visits as described in the protocol.
5. Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study.
6. Note: Other protocol-defined Inclusion Criteria apply.

Exclusion criteria 6

1. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants.
2. Body weight <40 kilograms at screening visit.
3. Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol.
4. Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol.
5. Known hereditary complement deficiency.
6. Note: Other protocol-defined Exclusion Criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in Lactate Dehydrogenase (LDH) during treatment period (TP) from baseline to week 28.

Secondary endpoints 19

1. Normalization of LDH through week 52.
2. Adequate control of hemolysis (LDH ≤1.5 × ULN) through week 52.
3. Transfusion avoidance through week 52.
4. Hemoglobin stabilization through week 52.
5. Change in hemoglobin through week 52.
6. Change in fatigue through week 52, as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale.
7. Occurrence of all Adverse Events (AEs) through week 52.
8. Severity of all AEs through week 52.
9. Occurrence of all Treatment-Emergent Adverse Events (TEAEs) through week 52.
10. Severity of all TEAEs through week 52.
11. Change from baseline in Total Complement Hemolytic Activity Assay (CH50) through week 52.
12. Concentrations of total pozelimab through week 52.
13. Concentrations of cemdisiran through week 52.
14. Concentrations of total C5 through week 52.
15. Incidence of Anti-Drug Antibody (ADA) to pozelimab through week 52.
16. Magnitude of ADA to pozelimab though week 52.
17. Incidence of ADA to cemdisiran through week 52.
18. Magnitude of ADA to cemdisiran through week 52.
19. Percent change in LDH during extension treatment period (EP) from baseline to week 24 and week 52.

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 5

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Results and documents

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

Documents 21 files

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

Application history

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