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 (ACCESS-1)

A Randomized, Open-Label, C5 Inhibitor-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Ravulizumab; Drug: Pozelimab; Drug: Cemdisiran; Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 08270-070
    • Casa de Saude Santa Marcelina
  • São Paulo, Brazil, 01321-001
    • A Beneficencia Portuguesa de Sao Paulo, BP Mirante
  • São Paulo
    • Santo André, São Paulo, Brazil, 09060-650
      • Centro de Estudos e Pesquisas em Hematologia e Oncologia
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100032
      • Peking Union Medical College Hospital
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050034
      • Hospital Pablo Tobón Uribe
• Greece
  • Thessaloniki, Greece, 57010
    • George Papanikolaou Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University
• India
  • Jaipur, India, 302017
    • Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
  • Kerala
    • Kannur, Kerala, India, 670103
      • Malabar Cancer Center, Kerala
    • Kochi, Kerala, India, 682041
      • Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
  • Maharashtra
    • Mumbai, Maharashtra, India, 400022
      • K J Somaiya Super Specialty Hospital & Research Centre
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110085
      • Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
  • Punjab
    • Chandigarh, Punjab, India, 708248
      • Postgraduate Institute of Medical Education & Research (PGIMER)
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Sanjay Gandhi Postgraduate Institute of Medical Sciences
    • Lucknow, Uttar Pradesh, India, 226003
      • King George Hospital
• Italy
  • Turin, Italy, 10126
    • Hematology Citta della Salute e della Scienza di Torino
  • Firenze
    • Florence, Firenze, Italy, 50139
      • AOU Careggi
  • Roma
    • Rome, Roma, Italy, 00168
      • Fondazione Policlinico Universitario A. Gemelli - IRCCS
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8650
      • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Gifu
    • Ōgaki, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • University of Tsukuba Hospital
  • Osaka
    • Moriguchi, Osaka, Japan, 570-8540
      • Matsushita Memorial Hospital
  • Tokyo
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo
• Jordan
  • Amman, Jordan, 11942
    • Jordan University Hospital (JUH)
• Malaysia
  • Pahang
    • Kuantan, Pahang, Malaysia, 25200
      • Hospital Tg Ampuan Afzan
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Hospital Queen Elizabeth
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Servicio de Hematologia del Hospital Universitario de la Uanl
• Peru
  • Lima, Peru, 15072
    • Clinica San Felipe
• Philippines
  • Central Luzon
    • Quezon, Central Luzon, Philippines, 1011
      • St Lukes Medical Center
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr2 Bydgoszcz
  • Warsaw, Poland, 02-776
    • Institute of Hematology and Transfusion Medicine
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • University Clinical Center Medical University of Gdansk
• Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Ion Chiricuta Oncology Institute
  • Dolj
    • Craiova, Dolj, Romania, 200143
      • Municipal Hospital Filantropia
  • Mureș County
    • Târgu Mureş, Mureș County, Romania, 540136
      • Targu Mures Clinical County Emergency Hospital
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Seoul, South Korea, 07985
    • Ewha Womans University Mokdong Hospital
  • Seoul, South Korea, 02841
    • Korea University Hospital
  • Seoul, South Korea, 065791
    • Seoul St. Mary's Hospital - The Catholic University of Korea
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Ajou University Medical Center
    • Suwon, Gyeonggi-do, South Korea, 16247
      • St. Vincent Hospital
  • Namdong-Gu
    • Incheon, Namdong-Gu, South Korea, 21565
      • Gachon University Gil Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Murcia, Spain, 30008
    • Hospital General JM Morales Meseguer
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital Universitario Basurto
• Taiwan
  • Changhua, Taiwan, 500-06
    • Changhua Christian Hospital
  • Hualien City, Taiwan, 97002
    • Hualien Tzu Chi Hospital
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 4070
    • Taichung Veterans General Hospital (VGHTC)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital
  • Taipei, Taiwan, 100229
    • National Taiwan University Hospital
  • Central Taiwan
    • Taichung, Central Taiwan, Taiwan, 40447
      • China Medical University Hospital
  • Hunan Province
    • Taoyuan, Hunan Province, Taiwan, 33305
      • Chang Gung Memorial Hospital - Linkou Branch
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Chiang Mai, Thailand, 50200
    • Chaing Mai University
  • Khon Kaen, Thailand, 40002
    • Faculty of Medicine Khon Kaen University
  • Changwat Songkhla
    • Hat Yai, Changwat Songkhla, Thailand, 90110
      • Clinical Research Center, Faculty of Medicine, Prince of Songkla University
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34418
    • Istanbul University
  • Izmir, Turkey (Türkiye), 35100
    • Ege University
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James Hospital
• United States
  • California
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope & Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
2. Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
3. LDH level ≥2 × ULN at the screening visit
4. 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

Key Exclusion Criteria:

1. 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
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. Body weight <40 kilograms at screening visit
4. Planned use of any complement inhibitor therapy other than study drugs during the treatment period
5. 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.
6. Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B).
7. 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
8. 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
9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Randomized 1:1	Drug: Ravulizumab; Administered Intravenous (IV) per the protocol; Other Names: Ultomiris; ALXN1210; Drug: Pozelimab; Administered IV and subcutaneous (SC) per the protocol; Other Names: REGN3918; Drug: Cemdisiran; Administered SC per the protocol; Other Names: ALN-CC5
Experimental: Cohort B; Randomized 1:1	Drug: Pozelimab; Administered IV and subcutaneous (SC) per the protocol; Other Names: REGN3918; Drug: Cemdisiran; Administered SC per the protocol; Other Names: ALN-CC5; Drug: Eculizumab; Administered IV per the protocol; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breakthrough hemolysis	Cohort A and B LDH ≥2 × ULN per the protocol	From post-baseline day 1 through week 26
Hemoglobin stabilization	Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol	From day 1 (post-baseline) through week 26
Normalization of LDH	Cohort A and B LDH ≤1.0 × ULN per the protocol	Between week 8 through week 26, inclusive
Transfusion avoidance	Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.	Day 1 through week 26
Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale	Cohort A and B FACIT-Fatigue Scale is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.	From baseline to week 26
Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30	Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	From baseline to week 26
Percent change in LDH	Cohort B	From baseline to week 26
Rate of RBC transfused	Cohort A and B Per protocol algorithm	Post-baseline Day 1 through week 26
Number of units of RBC transfused	Cohort A and B Per protocol algorithm	Post-baseline Day 1 through week 26
Time to first LDH ≤1.5 × ULN	Cohort A and B	Up to Week 26
Time to first LDH ≤1.0 × ULN	Cohort A and B	Up to Week 26
Percentage of days with LDH ≤1.5 × ULN	Cohort A and B	Between week 8 and week 26, inclusive
Change in hemoglobin levels	Cohort A and B	From baseline to week 26
Incidence and severity of treatment emergent serious adverse events (SAEs)	Cohort A and B	Up to 26 weeks
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest	Cohort A and B	Up to 26 weeks
Incidence and severity of TEAEs leading to treatment discontinuation	Cohort A and B	Up to 26 weeks
Change in total CH50	Cohort A and B	From baseline to week 26
Percent change in total CH50	Cohort A and B	From baseline to week 26
Concentration of total C5 in plasma	Cohort A and B	Up to 60 weeks
Concentrations of total pozelimab in serum	Cohort A and B	Up to 60 weeks
Concentrations of cemdisiran in plasma	Cohort A and B	Up to 60 weeks
Concentrations of total ravulizumab in serum	Cohort A	Up to 34 weeks
Concentrations of total eculizumab in serum	Cohort B	Up to 30 weeks
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab	Cohort A and B	Up to 60 weeks
Incidence of treatment emergent ADAs to cemdisiran	Cohort A and B	Up to 60 weeks
Maintenance of adequate control of hemolysis	Cohort A and B LDH ≤1.5 × ULN	From week 8 through week 26, inclusive
Adequate control of hemolysis	Cohort A LDH ≤1.5 × ULN	From week 8 through week 26, inclusive
Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)	Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	From baseline to week 26

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Informational Website

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): October 26, 2026

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PNH
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; ravulizumab; eculizumab
• Other Study ID Numbers: R3918-PNH-2021; 2020-004486-40 (EudraCT Number); 2023-509657-31-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing 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.

• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No