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

NCT ID: NCT05131204

Last Updated: 2025-04-08

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-06

Study Completion Date

2023-07-12

Brief Summary

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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

Detailed Description

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Conditions

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Paroxysmal Nocturnal Hemoglobinuria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pozelimab and Cemdisiran

Randomized 1:1

Group Type EXPERIMENTAL

Cemdisiran

Intervention Type DRUG

Administered per protocol

Eculizumab

Intervention Type DRUG

Administered per protocol

Pozelimab

Intervention Type DRUG

Administered per protocol

Ravulizumab

Intervention Type DRUG

Administered per protocol

Anti-C5 standard-of-care

Randomized 1:1

Group Type EXPERIMENTAL

Eculizumab

Intervention Type DRUG

Administered per protocol

Ravulizumab

Intervention Type DRUG

Administered per protocol

Interventions

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Cemdisiran

Administered per protocol

Intervention Type DRUG

Eculizumab

Administered per protocol

Intervention Type DRUG

Pozelimab

Administered per protocol

Intervention Type DRUG

Ravulizumab

Administered per protocol

Intervention Type DRUG

Other Intervention Names

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ALN-CC5 Soliris REGN3918 ALXN1210 Ultomiris

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor

Exclusion Criteria

1. 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
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. Body weight \< 40 kilograms at screening visit
4. 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
5. 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.
6. Any contraindication for receiving Neisseria meningitidis vaccination.
7. Positive for hepatitis B, and/ or hepatitis C as described in the protocol
8. 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
9. 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.
10. Patients with functional or anatomic asplenia
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Regeneron Research Facility

Whittier, California, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.trialsummaries.com/

A Plain Language Summary is available on TrialSummaries.com

Other Identifiers

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2020-002761-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R3918-PNH-2022

Identifier Type: -

Identifier Source: org_study_id

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