A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works

NCT05744921 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: R3918-PNH-20502021-004931-102023-510336-36-00
• Study Type: interventional
• Target: 202
• Locations: 19 countries
• Sites: 43

Brief Summary

This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as "study drugs" in this section. This study is looking at several other research questions, including:

• How effective is the pozelimab + cemdisiran combination?
• What side effects may happen from taking the study drugs?
• How much of each study drug is in the blood at different times?
• Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (7)

• Incidence of treatment-emergent serious adverse events (SAEs)

  An SAE is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect. * Is an important medical event

  Up to week 108

• Severity of treatment-emergent SAEs

  Up to week 108

• Incidence of treatment emergent adverse events of special interest (AESIs)

  An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it

  Up to week 108

• Severity of treatment emergent AESIs

  Up to week 108

• Incidence of adverse events (AEs) leading to permanent treatment discontinuation

  Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.

  Up to week 108

• Severity of adverse events (AEs) leading to permanent treatment discontinuation

  Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.

  Up to week 108

• Percent change from baseline in lactate dehydrogenase (LDH)

  Baseline to week 36

Secondary Outcomes (53)

• Adequate control of hemolysis (LDH ≤1.5 × ULN)

  Post-baseline through week 108

• Transfusion avoidance

  Post-baseline through week 36

• Transfusion avoidance

  Post-baseline through week 48

• Transfusion avoidance

  Post-baseline through week 76

• Transfusion avoidance

  Post-baseline through week 108

Study Arms (2)

PNH Transition Patients

EXPERIMENTAL

Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 \[NCT05133531\])

Drug: Pozelimab; Drug: Cemdisiran

C5 Polymorphism Patients

EXPERIMENTAL

Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1.

Drug: Pozelimab; Drug: Cemdisiran

Interventions

Cemdisiran DRUG

Administered per the protocol

Also known as: ALN-CC5

C5 Polymorphism Patients; PNH Transition Patients

Pozelimab DRUG

Administered per the protocol

Also known as: REGN3918

C5 Polymorphism Patients; PNH Transition Patients

Eligibility Criteria

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

You may qualify if:

• Patients Entering from the Parent Study
• Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021\[NCT05133531\]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
• Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
• Patients Entering with C5 polymorphism
• Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
• Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
• Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
• LDH level ≥2 × upper limit of normal (ULN) at the screening visit
• Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol

You may not qualify if:

• Patients Entering from the Parent Study
• Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
• Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study
• Patients Entering with C5 polymorphism
• Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
• Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol
• Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
• Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
• Known hereditary complement deficiency
• Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
• Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (43)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Hospital Pablo Tobon Uribe

Medellín, Antioquia, 050034, Colombia

RECRUITING

Semmelweis University/Semmelweis Egyetem

Budapest, 1083, Hungary

RECRUITING

Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims

Kochi, Kerala, 682041, India

RECRUITING

K J Somaiya Super Specialty Hospital & Research Centre

Mumbai, Maharashtra, 400022, India

RECRUITING

Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus

New Delhi, National Capital Territory of Delhi, 110085, India

RECRUITING

Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)

Jaipur, 302017, India

RECRUITING

Aou Careggi

Florence, Firenze, 50139, Italy

RECRUITING

SC Hematology, AOU Città della Salute e della Scienza di Torino

Torino, 10126, Italy

RECRUITING

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, 466-8650, Japan

WITHDRAWN

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

RECRUITING

Jordan University Hospital (JUH)

Amman, 11942, Jordan

RECRUITING

Hospital Tg Ampuan Afzan

Kuantan, Pahang, 25200, Malaysia

RECRUITING

Hospital Queen Elizabeth

Kota Kinabalu, Sabah, 88200, Malaysia

RECRUITING

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

RECRUITING

Clinica San Felipe

Lima, 15072, Peru

RECRUITING

St Lukes Medical Center

Quezon City, National Capital Region, 1634, Philippines

RECRUITING

In-Vivo Sp. z o.o.

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-048, Poland

RECRUITING

University Clinical Center Medical University of Gdansk

Gdansk, Pomeranian Voivodeship, 80-214, Poland

RECRUITING

Szpital Uniwersytecki Nr2 Bydgoszcz

Bydgoszcz, 85-168, Poland

RECRUITING

Prof Dr Ion Chiricuta Cancer Institute

Cluj-Napoca, Cluj, 400015, Romania

RECRUITING

National University Hospital

Singapore, 119074, Singapore

RECRUITING

St. Vincent Hospital

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Ajou University Medical Center

Suwon, Gyeonggi-do, 16499, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, Namdong-Gu, 21565, South Korea

RECRUITING

Pusan National University Hospital

Busan, 49241, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Ewha Womans University Mokdong Hospital

Seoul, 07985, South Korea

RECRUITING

Hospital Universitario Basurto

Bilbao, Vizcaya, 48013, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

China Medical University Hospital

Taichung, Central Taiwan, 40447, Taiwan

RECRUITING

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan District, Hunan Province, 33305, Taiwan

RECRUITING

Hualien Tzu Chi Hospital

Hualien City, 97002, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, 11490, Taiwan

RECRUITING

Prince Of Songkla Hospital, Prince Of Songkhla University

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

RECRUITING

Chiang Mai University

Chiang Mai, 50200, Thailand

RECRUITING

Faculty of Medicine Khon Kaen University

Khon Kaen, 40002, Thailand

RECRUITING

Ege University Faculty of Medicine

Bornova, İzmir, 35100, Turkey (Türkiye)

RECRUITING

Istanbul University

Istanbul, 34418, Turkey (Türkiye)

RECRUITING

Leeds Teaching Hospitals NHS Trust - St. James Institute of Oncology

Leeds, LS97TF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: February 27, 2023
• Study Start: March 7, 2023
• Primary Completion (Estimated): February 26, 2029
• Study Completion (Estimated): February 26, 2029
• Last Updated: March 18, 2026

Record last verified: 2026-03

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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), * the legal authority to share the data, and * 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

JO (1); CO (1); HU (1); KR (7); TU (2); TW (5); JP (2); IN (4); GB (1); PL (3); PH (1); IT (2); SG (1); RO (1); PE (1); TH (4); ES (2); CA (1); MY (3)