A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment

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]

Trial duration

24 Aug 2022 → ongoing

Decision date (initial)

2025-01-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509657-31-00

EudraCT number

2020-004486-40

ClinicalTrials.gov

NCT05133531

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Cohort A: To describe the effect of pozelimab + cemdisiran combination treatment compared to ravulizumab treatment on hemolysis, as assessed by lactate dehydrogenase (LDH), over a 26-week treatment period in patients with active PNH who are complement inhibitor treatment-naive or have not recently received complement inhibitor therapy.

Cohort B: To evaluate the effect of pozelimab + cemdisiran combination treatment compared to eculizumab treatment on hemolysis, as assessed by suppression of LDH, and transfusion avoidance over a 26- week treatment period in patients with active PNH who are complement inhibitor treatment-naive or have not recently received complement inhibitor therapy.

Secondary objectives 6

1. Cohort A: Describe the effect of pozelimab + cemdisiran combination treatment versus ravulizumab on the following: -Measures of hemolysis -Transfusion parameters -Hemoglobin levels -Fatigue as assessed by clinical outcome assessments (COAs) -Health-related quality of life (HRQoL) as assessed by COAs -Safety and tolerability -Complement activation
2. Cohort A: To assess the concentrations of total pozelimab and total ravulizumab in serum and cemdisiran and total C5 protein in plasma
3. Cohort A: To assess the immunogenicity of pozelimab and cemdisiran
4. Cohort B: Evaluate the effect of pozelimab + cemdisiran combination treatment versus eculizumab on the following: -Measures of hemolysis -Transfusion parameters -Hemoglobin levels-Fatigue as assessed by COAs -HRQoL as assessed by COAs -Safety and tolerability -Complement activation
5. Cohort B: To assess the concentrations of total pozelimab and total eculizumab in serum and cemdisiran and total C5 protein in plasma
6. Cohort B: To assess the immunogenicity of pozelimab and cemdisiran

Conditions and MedDRA coding

Paroxysmal nocturnal haemoglobinuria (PNH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
2. Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
3. LDH level ≥2 × ULN at the screening visit
4. 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 Note: Other protocol-defined Inclusion Criteria apply

Exclusion criteria 9

1. Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. Body weight <40 kilograms at screening visit
4. Planned use of any complement inhibitor therapy other than study drugs during the treatment period
5. Not meeting meningococcal vaccination requirements and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol.
6. Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B)
7. Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine [serotype ACWY] or the second dose of the serotype B meningococcal vaccine [when available] is less than 2 weeks prior to study treatment initiation) as described in the protocol.
8. Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period
9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases Note: Other protocol-defined Exclusion Criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Cohort A: Percent change in lactate dehydrogenase (LDH)
2. Cohort B: Adequate control of hemolysis (defined as LDH ≤1.5 × ULN) at each visit
3. Cohort B: Transfusion avoidance (not requiring a red blood cell (RBC) transfusion per the protocol)

Secondary endpoints 27

1. Maintenance of adequate control of hemolysis (defined as LDH ≤1.5 × ULN) (Cohort A and B)
2. Breakthrough hemolysis (defined as LDH ≥2 × ULN per the protocol) (Cohort A and B)
3. Adequate control of hemolysis (defined as LDH ≤1.5 × ULN) (Cohort A)
4. Hemoglobin stabilization (defined as patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol) (Cohort A and B)
5. Normalization of LDH (defined as LDH ≤1.0 × ULN per the protocol) (Cohort A and B)
6. Transfusion Avoidance (defined as Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values) (Cohort A)
7. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale (Cohort A and B)
8. Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Cohort A and B)
9. Change in global health status (GHS)/QoL scale score on the EORTC-QLC- C30 (Cohort A and B)
10. Percent change in LDH (Cohort B)
11. Rate of RBC transfused per protocol algorithm (Cohort A and B)
12. Number of units of RBC transfused per protocol algorithm (Cohort A and B)
13. Time to first LDH ≤1.5 × ULN (Cohort A and B)
14. Time to first LDH ≤1.0 × ULN (Cohort A and B)
15. Percentage of days with LDH ≤1.5 × ULN (Cohort A and B)
16. Change in hemoglobin levels (Cohort A and B)
17. Incidence and severity of treatment emergent serious adverse events (SAEs) (Cohort A and B)
18. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest (Cohort A and B)
19. Incidence and severity of TEAEs leading to treatment discontinuation (Cohort A and B)
20. Change in total CH50 (Cohort A and B)
21. Percent change in total CH50 (Cohort A and B)
22. Concentration of total C5 in plasma (Cohort A and B)
23. Concentrations of total pozelimab in serum (Cohort A and B)
24. Concentrations of cemdisiran in plasma (Cohort A and B)
25. Concentrations of total ravulizumab (Cohort A) and total eculizumab (Cohort B) in serum
26. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab (Cohort A and B)
27. Incidence of treatment emergent ADAs to cemdisiran (Cohort A and B)

Investigational products

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

Test 2

Comparator 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

Clinical Trial Information

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 11

Locations

6 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 54 files

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

Application history

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