Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

NCT04811716 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: R3918-PNH-20922020-005005-17
• Study Type: interventional
• Target: 24
• Locations: 6 countries
• Sites: 13

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP) The secondary objectives of the study are:

• To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of total complement hemolysis activity (CH50)
• To evaluate the effect of the combination treatment on hemoglobin levels
• To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
• To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life
• To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma
• To assess immunogenicity to pozelimab and cemdisiran
• To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP)
• To assess safety after treatment intensification with pozelimab and cemdisiran

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

  Open Label Treatment Period (OLTP)

  Through Week 28

Secondary Outcomes (57)

• Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period

  End of treatment period, approximately 28 Weeks

• Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28

  Baseline (Day 1) through Week 28

• Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28

  Week 4 through Week 28

• Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28

  Day 1 through Week 28

• Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28

  Baseline (Day 1) through Week 28

Study Arms (2)

Pozelimab Q4W + Cemdisiran

EXPERIMENTAL

Drug: Pozelimab; Drug: Cemdisiran

Pozelimab Q2W + Cemdisiran

EXPERIMENTAL

Drug: Pozelimab; Drug: Cemdisiran

Interventions

Pozelimab DRUG

Administered Sub-cutaneous (SC) per protocol

Also known as: REGN3918

Pozelimab Q2W + Cemdisiran; Pozelimab Q4W + Cemdisiran

Cemdisiran DRUG

Administered SC per protocol

Also known as: ALN-CC5

Pozelimab Q2W + Cemdisiran; Pozelimab Q4W + Cemdisiran

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)

You may not qualify if:

• Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol
• Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol
• Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
• Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant
• Known hypersensitivity to cemdisiran or any component of cemdisiran formulation

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (13)

Prince of Wales Hospital

Hong Kong, New Territories, 550540, Hong Kong

Location

D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet

Budapest, Nagyvárad Tér 1, 1907, Hungary

Location

Hospital Miri

Miri, Sarawak, 98000, Malaysia

Location

Hospital Sibu

Sibu, Sarawak, 96000, Malaysia

Location

Hospital Sultanah Nur Zahirah

Kuala Terengganu, Terengganu, 20400, Malaysia

Location

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei University College of Medicine, Severance Hospital

Seoul, 3722, South Korea

Location

Ewha Womans University Medical Centre

Seoul, 7985, South Korea

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan, 333, Taiwan

Location

St. James's University Hospital

Leeds, West Yorkshire, LS97TF, United Kingdom

Location

Related Publications (1)

• Jang JH, Wong RSM, Hartford C, Pavani R, Aurand L, Nguyen Q, Mohan K, Meagher K, Sherman S, Rofail D, Perlee L, Souttou A, Kelly RJ. Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria. EJHaem. 2025 Jul 24;6(4):e70095. doi: 10.1002/jha2.70095. eCollection 2025 Aug.

  PMID: 40708708 DERIVED

Related Links

• A Plain Language Summary is available on TrialSummaries.com

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 23, 2021
• Study Start: July 29, 2021
• Primary Completion: October 25, 2022
• Study Completion: October 18, 2023
• Last Updated: April 8, 2025
• Results First Posted: January 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

GB (1); TW (2); HU (1); KR (5); MY (3); HK (1)