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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— ACCESS-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05133531
• Other study ID #: R3918-PNH-2021
• Secondary ID: 2020-004486-4020
• Status: Recruiting
• Phase: Phase 3
• Start date: August 1, 2022
• Est. completion date: March 29, 2027

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with PNH and how the combination compares with 2 existing treatments, one called ravulizumab and the other called 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: March 29, 2027
• Est. primary completion date: March 29, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (when available) 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 vaccination is less than 2 weeks prior to study treatment initiation)

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• Ravulizumab
Administered Intravenous (IV) per the protocol
• Pozelimab
Administered IV and subcutaneous (SC) per the protocol
• Cemdisiran
Administered SC per the protocol
• Eculizumab
Administered IV per the protocol

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
Greece	George Papanikolaou Hospital	Thessaloniki
Hungary	Semmelweis Egyetem	Budapest
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Japan	Panasonic Health Insurance Organization Matsushita Memorial Hospital	Moriguchi-city	Osaka
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital	Nagoya	Aichi
Japan	Ogaki Municipal Hospital	Ogaki city	Gifu
Japan	NTT Medical Center Tokyo	Shinagawa-ku	Tokyo
Japan	University of Tsukuba Hospital	Tsukuba-shi	Ibaraki
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Ajou University Medical Center	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Korea University Hospital	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	St. Vincent Hospital	Suwon
Malaysia	Hospital Ampang	Ampang	Selangor
Malaysia	Queen Elizabeth Hospital - Kota Kinabalu	Kota Kinabalu
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Mexico	Hospital Universitario Dr. Jose Eleuterio González	Monterrey	Nuevo León
Poland	Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Romania	Prof Dr I Chiricuta Institute of Oncology	Cluj-Napoca	Cluj
Romania	Filantropia Municipal Clinical Hospital	Craiova	Dolj
Romania	Targu-Mures Emergency Clinical County Hospital	Targu Mures	Mures
Singapore	National University Hospital	Singapore
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Basurto	Bilbao	Vizcaya
Taiwan	Changhua Christian Hospital	Changhua City
Taiwan	Hualien Tzu Chi Hospital	Hualien City
Taiwan	Kaohsiung Medical University - Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital - PPDS	Taichung
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chang Gung Hospital	Taoyuan City
Taiwan	National Taiwan University Hospital	Tapei City
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Songklanagarind Hospital Prince of Songkla University	Hat Yai	Songkhla
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Rajavithi Hospital	Ratchathewi	Krung Thep Maha Nakhon-Bangkok
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
United Kingdom	St James University Hospital	Leeds
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in lactate dehydrogenase (LDH)	Cohort A	From baseline to week 26
Primary	Transfusion avoidance	Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol	From post-baseline day 1 through week 26
Primary	Maintenance of adequate control of hemolysis	Cohort B LDH =1.5 × ULN	From week 8 through week 26, inclusive
Secondary	Maintenance of adequate control of hemolysis	Cohort A LDH =1.5 × ULN	From week 8 through week 26, inclusive
Secondary	Breakthrough hemolysis	Cohort A and B LDH =2 × ULN per the protocol	From post-baseline day 1 through week 26
Secondary	Adequate control of hemolysis	Cohort A and B LDH =1.5 × ULN	From week 8 through week 26, inclusive
Secondary	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
Secondary	Normalization of LDH	Cohort A and B LDH =1.0 × ULN per the protocol	Between week 8 through week 26, inclusive
Secondary	Transfusion avoidance	Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.	Day 1 through week 26
Secondary	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
Secondary	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."	Change from baseline to week 26
Secondary	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
Secondary	Percent change in LDH	Cohort B	From baseline to week 26
Secondary	Rate of RBC transfused	Cohort A and B Per protocol algorithm	Post-baseline Day 1 through week 26
Secondary	Number of units of RBC transfused	Cohort A and B Per protocol algorithm	Post-baseline Day 1 through week 26
Secondary	Time to first LDH =1.5 × ULN	Cohort A and B	Up to Week 26
Secondary	Time to first LDH =1.0 × ULN	Cohort A and B	Up to Week 26
Secondary	Percentage of days with LDH =1.5 × ULN	Cohort A and B	Between week 8 and week 26, inclusive
Secondary	Change in hemoglobin levels	Cohort A and B	From baseline to week 26
Secondary	Incidence and severity of treatment emergent serious adverse events (SAEs)	Cohort A and B	Up to 26 weeks
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest	Cohort A and B	Up to 26 weeks
Secondary	Incidence and severity of TEAEs leading to treatment discontinuation	Cohort A and B	Up to 26 weeks
Secondary	Change in total CH50	Cohort A and B	From baseline to week 26
Secondary	Percent change in total CH50	Cohort A and B	From baseline to week 26
Secondary	Concentration of total C5 in plasma	Cohort A and B	Up to 60 weeks
Secondary	Concentrations of total pozelimab in serum	Cohort A and B	Up to 60 weeks
Secondary	Concentrations of cemdisiran in plasma	Cohort A and B	Up to 60 weeks
Secondary	Concentrations of total ravulizumab in serum	Cohort A	Up to 34 weeks
Secondary	Concentrations of total eculizumab in serum	Cohort B	Up to 30 weeks
Secondary	Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab	Cohort A and B	Up to 52 weeks
Secondary	Incidence of treatment emergent ADAs to cemdisiran	Cohort A and B	Up to 52 weeks