Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

NCT05131204 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: R3918-PNH-20222020-002761-33
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is: To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy The secondary objectives of the study are to:

• Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:
• Transfusion requirements and transfusion parameters
• Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
• Hemoglobin levels
• Fatigue as assessed by Clinical Outcome Assessments (COAs)
• Health-related quality of life (HRQoL) as assessed by COAs
• Safety and tolerability
• To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
• To assess the immunogenicity of pozelimab and cemdisiran

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (1)

• Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36

  From baseline to week 36

Secondary Outcomes (32)

• Percentage of Participants With Transfusion Avoidance After Day 1 Through Week 36

  Day 1 through week 36

• Percentage of Participants With Transfusion Avoidance From Week 4 Through Week 36

  Week 4 through week 36

• Percentage of Participants With Breakthrough Hemolysis After Day 1 Through Week 36

  Day 1 through week 36

• Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 36

  Week 4 (day 29) through week 36

• Percentage of Participants With Hemoglobin Stabilization After Day 1 Through Week 36

  Day 1 through week 36

Study Arms (2)

Pozelimab and Cemdisiran

EXPERIMENTAL

Randomized 1:1

Drug: Cemdisiran; Drug: Eculizumab; Drug: Pozelimab; Drug: Ravulizumab

Anti-C5 standard-of-care

EXPERIMENTAL

Randomized 1:1

Drug: Eculizumab; Drug: Ravulizumab

Interventions

Cemdisiran DRUG

Administered per protocol

Also known as: ALN-CC5

Pozelimab and Cemdisiran

Eculizumab DRUG

Administered per protocol

Also known as: Soliris

Anti-C5 standard-of-care; Pozelimab and Cemdisiran

Pozelimab DRUG

Administered per protocol

Also known as: REGN3918

Pozelimab and Cemdisiran

Ravulizumab DRUG

Administered per protocol

Also known as: ALXN1210, Ultomiris

Anti-C5 standard-of-care; Pozelimab and 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 PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
• Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor

You may not qualify if:

• Patients with a screening LDH \>1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
• Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
• Body weight \< 40 kilograms at screening visit
• Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
• Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
• Any contraindication for receiving Neisseria meningitidis vaccination.
• Positive for hepatitis B, and/ or hepatitis C as described in the protocol
• History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
• Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
• Patients with functional or anatomic asplenia

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (1)

Regeneron Research Facility

Whittier, California, 90603, United States

Location

Related Links

• A Plain Language Summary is available on TrialSummaries.com

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab; ravulizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

20Dec2022 - Due to feasibility challenges related to enrollment and not due to efficacy or safety concerns, the sponsor terminated the study early and discontinued participant enrollment.

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: November 23, 2021
• Study Start: October 6, 2022
• Primary Completion: July 12, 2023
• Study Completion: July 12, 2023
• Last Updated: April 8, 2025
• Results First Posted: September 19, 2024

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

US (1)