Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy

NCT04888507 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: R3918-PNH-201052020-005006-25
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy 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 CH50
• To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran
• To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
• To evaluate the effect of the combination treatment on hemoglobin levels
• To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL)
• To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma
• To assess the immunogenicity of pozelimab and cemdisiran
• To assess safety after dose intensification
• To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (1)

• OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to Day 225

Secondary Outcomes (57)

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

  Screening (Day 1) through Day 225

• OLTP: Percent Change in LDH From Pre-treatment Through Day 29

  Screening (Day 1) through Day 29

• OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32

  Baseline through Week 32

• OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32

  Week 4 through Week 32

• OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32

  Baseline through Week 32

Study Arms (1)

Pozelimab+Cemdisiran

EXPERIMENTAL

Drug: Pozelimab; Drug: Cemdisiran

Interventions

Pozelimab DRUG

Intravenous (IV) loading dose (once) followed after 30 minutes by sub-cutaneous (SC) administration

Also known as: REGN3918

Pozelimab+Cemdisiran

Cemdisiran DRUG

SC administration

Also known as: ALN-CC5

Pozelimab+Cemdisiran

Eligibility Criteria

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

You may qualify if:

• Diagnosis of paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing
• Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit

You may not qualify if:

• History of bone marrow transplantation or receipt of an organ transplant
• Body weight \<40 kg at screening
• Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol
• Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study
• Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25%
• No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment
• Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
• 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
• Documented positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol
• Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
• Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol
• Anticipated need for major surgery during the study

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (1)

Regeneron Study Site

Leeds, LS9 7TF, United Kingdom

Location

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: May 17, 2021
• Study Start: July 8, 2021
• Primary Completion: May 5, 2022
• Study Completion: May 4, 2023
• Last Updated: August 29, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-08

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)