A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment

NCT05133531 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: R3918-PNH-20212020-004486-402023-509657-31-00
• Study Type: interventional
• Target: 202
• Locations: 24 countries
• Sites: 68

Brief Summary

This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including:

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

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

Outcome Measures

Primary Outcomes (3)

• Percent change in lactate dehydrogenase (LDH)

  Cohort A

  From baseline to week 26

• Transfusion avoidance

  Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol

  From post-baseline day 1 through week 26

• Adequate control of hemolysis

  Cohort B LDH ≤1.5 × ULN at each visit

  From week 8 through week 26, inclusive

Secondary Outcomes (28)

• Maintenance of adequate control of hemolysis

  From week 8 through week 26, inclusive

• Breakthrough hemolysis

  From post-baseline day 1 through week 26

• Adequate control of hemolysis

  From week 8 through week 26, inclusive

• Hemoglobin stabilization

  From day 1 (post-baseline) through week 26

• Normalization of LDH

  Between week 8 through week 26, inclusive

Study Arms (2)

Cohort A

EXPERIMENTAL

Randomized 1:1

Drug: Ravulizumab; Drug: Pozelimab; Drug: Cemdisiran

Cohort B

EXPERIMENTAL

Randomized 1:1

Drug: Pozelimab; Drug: Cemdisiran; Drug: Eculizumab

Interventions

Ravulizumab DRUG

Administered Intravenous (IV) per the protocol

Also known as: ALXN1210, Ultomiris

Cohort A

Pozelimab DRUG

Administered IV and subcutaneous (SC) per the protocol

Also known as: REGN3918

Cohort A; Cohort B

Cemdisiran DRUG

Administered SC per the protocol

Also known as: ALN-CC5

Cohort A; Cohort B

Eculizumab DRUG

Administered IV per the protocol

Also known as: Soliris

Cohort B

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 high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
• Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
• LDH level ≥2 × ULN at the screening visit
• Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol

You may not qualify if:

• Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening
• Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
• Body weight \<40 kilograms at screening visit
• Planned use of any complement inhibitor therapy other than study drugs during the treatment period
• Not meeting meningococcal vaccination requirements and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol.
• Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B).
• Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab \[Cohort A\] or eculizumab \[Cohort B\] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine \[serotype ACWY\] or the second dose of the serotype B meningococcal vaccine \[when available\] is less than 2 weeks prior to study treatment initiation) as described in the protocol
• 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 history of active, uncontrolled, ongoing systemic autoimmune diseases

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (68)

The Oncology Institute of Hope & Innovation

Whittier, California, 90602, United States

Location

Centro de Estudos e Pesquisas em Hematologia e Oncologia

Santo André, São Paulo, 09060-650, Brazil

Location

A Beneficencia Portuguesa de Sao Paulo, BP Mirante

São Paulo, 01321-001, Brazil

Location

Casa de Saude Santa Marcelina

São Paulo, 08270-070, Brazil

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Hospital Pablo Tobon Uribe

Medellín, Antioquia, 050034, Colombia

Location

George Papanikolaou Hospital

Thessaloniki, 57010, Greece

Location

Semmelweis University

Budapest, 1083, Hungary

Location

Malabar Cancer Center, Kerala

Kannur, Kerala, 670103, India

Location

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

Kochi, Kerala, 682041, India

Location

K J Somaiya Super Specialty Hospital & Research Centre

Mumbai, Maharashtra, 400022, India

Location

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

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

Location

Postgraduate Institute of Medical Education & Research (PGIMER)

Chandigarh, Punjab, 708248, India

Location

King George Hospital

Lucknow, Uttar Pradesh, 226003, India

Location

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, 226014, India

Location

Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)

Jaipur, 302017, India

Location

Aou Careggi

Florence, Firenze, 50139, Italy

Location

Fondazione Policlinico Universitario A. Gemelli - IRCCS

Rome, Roma, 00168, Italy

Location

Hematology Citta della Salute e della Scienza di Torino

Turin, 10126, Italy

Location

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, 466-8650, Japan

Location

Ogaki Municipal Hospital

Ōgaki, Gifu, 503-8502, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Matsushita Memorial Hospital

Moriguchi, Osaka, 570-8540, Japan

Location

NTT Medical Center Tokyo

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Jordan University Hospital (JUH)

Amman, 11942, Jordan

Location

Hospital Tg Ampuan Afzan

Kuantan, Pahang, 25200, Malaysia

Location

Hospital Queen Elizabeth

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

Servicio de Hematologia del Hospital Universitario de la Uanl

Monterrey, Nuevo León, 64460, Mexico

Location

Clinica San Felipe

Lima, 15072, Peru

Location

St Lukes Medical Center

Quezon, Central Luzon, 1011, Philippines

Location

University Clinical Center Medical University of Gdansk

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Szpital Uniwersytecki Nr2 Bydgoszcz

Bydgoszcz, 85-168, Poland

Location

Institute of Hematology and Transfusion Medicine

Warsaw, 02-776, Poland

Location

Ion Chiricuta Oncology Institute

Cluj-Napoca, Cluj, 400015, Romania

Location

Municipal Hospital Filantropia

Craiova, Dolj, 200143, Romania

Location

Targu Mures Clinical County Emergency Hospital

Târgu Mureş, Mureș County, 540136, Romania

Location

National University Hospital

Singapore, 119074, Singapore

Location

St. Vincent Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Ajou University Medical Center

Suwon, Gyeonggi-do, 16499, South Korea

Location

Gachon University Gil Medical Center

Incheon, Namdong-Gu, 21565, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Korea University Hospital

Seoul, 02841, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St. Mary's Hospital - The Catholic University of Korea

Seoul, 065791, South Korea

Location

Ewha Womans University Mokdong Hospital

Seoul, 07985, South Korea

Location

Hospital Universitario Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General JM Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

China Medical University Hospital

Taichung, Central Taiwan, 40447, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan, Hunan Province, 33305, Taiwan

Location

Changhua Christian Hospital

Changhua, 500-06, Taiwan

Location

Hualien Tzu Chi Hospital

Hualien City, 97002, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 80756, Taiwan

Location

Taichung Veterans General Hospital (VGHTC)

Taichung, 4070, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100229, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Clinical Research Center, Faculty of Medicine, Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Chaing Mai University

Chiang Mai, 50200, Thailand

Location

Faculty of Medicine Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Istanbul University

Istanbul, 34418, Turkey (Türkiye)

Location

Ege University

Izmir, 35100, Turkey (Türkiye)

Location

St James Hospital

Leeds, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

ravulizumab; eculizumab

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

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 24, 2021
• Study Start: August 1, 2022
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): October 26, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

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 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

JP (5); ME (1); IN (8); PH (1); SG (1); US (1); PL (3); TU (2); CN (1); ES (4); MY (3); TW (9); RO (3); CA (1); TH (4); GB (1); CO (1); HU (1); IT (3); BR (3); KR (9); GR (1); JO (1); PE (1)