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

Official title

An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria

Overview

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)

Interventions

• Drug Pozelimab
  Administered per the protocol
• Drug Cemdisiran
  Administered per the protocol

Primary outcome measures

• Incidence of treatment-emergent serious adverse events (SAEs) [Time frame: Up to week 108]
• Severity of treatment-emergent SAEs [Time frame: Up to week 108]
• Incidence of treatment emergent adverse events of special interest (AESIs) [Time frame: Up to week 108]
• Severity of treatment emergent AESIs [Time frame: Up to week 108]
• Incidence of adverse events (AEs) leading to permanent treatment discontinuation [Time frame: Up to week 108]
• Severity of adverse events (AEs) leading to permanent treatment discontinuation [Time frame: Up to week 108]
• Percent change from baseline in lactate dehydrogenase (LDH) [Time frame: Baseline to week 36]

Secondary outcome measures (12)

• Adequate control of hemolysis (LDH ≤1.5 × ULN) [Time frame: Post-baseline through week 108]
• Transfusion avoidance [Time frame: Post-baseline through week 36]
• Transfusion avoidance [Time frame: Post-baseline through week 48]
• Transfusion avoidance [Time frame: Post-baseline through week 76]
• Transfusion avoidance [Time frame: Post-baseline through week 108]
• Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis) [Time frame: Post-baseline through week 36]
• Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis) [Time frame: Post-baseline through week 48]
• Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis) [Time frame: Post-baseline through week 76]
• Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis) [Time frame: Post-baseline through week 108]
• Hemoglobin stabilization [Time frame: Post-baseline through week 36]
• Hemoglobin stabilization [Time frame: Post-baseline through week 48]
• Hemoglobin stabilization [Time frame: Post-baseline through week 76]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

• Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
• 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

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 8 centers

• St. Vincent Hospital — Suwon
• Ajou University Medical Center — Suwon
• Gachon University Gil Medical Center — Incheon
• Pusan National University Hospital — Busan
• Severance Hospital Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul
• The Catholic University of Korea, Seoul St. Mary's Hospital — Seoul
• Ewha Womans University Mokdong Hospital — Seoul

Taiwan · 6 centers

• China Medical University Hospital — Taichung
• Chang Gung Memorial Hospital - Linkou Branch — Taoyuan
• Changhua Christian Hospital — Changhua
• Hualien Tzu Chi Hospital — Hualien City
• National Taiwan University Hospital — Taipei
• Tri-Service General Hospital — Taipei

India · 5 centers

• Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims — Kochi
• K J Somaiya Super Specialty Hospital & Research Centre — Mumbai
• Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus — New Delhi
• Postgraduate Institute of Medical Education & Research — Chandigarh
• Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC) — Jaipur

Thailand · 4 centers

• Prince Of Songkla Hospital, Prince Of Songkhla University — Hat Yai
• King Chulalongkorn Memorial Hospital — Bangkok
• Chiang Mai University — Chiang Mai
• Faculty of Medicine Khon Kaen University — Khon Kaen

Malaysia · 3 centers

• Hospital Tg Ampuan Afzan — Kuantan
• Hospital Queen Elizabeth — Kota Kinabalu
• Hospital Ampang — Ampang

Poland · 3 centers

• In-Vivo Sp. z o.o. — Bydgoszcz
• University Clinical Center Medical University of Gdansk — Gdansk
• Szpital Uniwersytecki Nr2 Bydgoszcz — Bydgoszcz

Italy · 2 centers

• Aou Careggi — Florence
• SC Hematology, AOU Città della Salute e della Scienza di Torino — Torino

Japan · 2 centers

• Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital — Nagoya
• University of Tsukuba Hospital — Tsukuba

Spain · 2 centers

• Hospital Universitario Basurto — Bilbao
• Hospital Clinic de Barcelona — Barcelona

Turkey (Türkiye) · 2 centers

• Ege University Faculty of Medicine — Bornova
• Istanbul University — Istanbul

Canada · 1 center

• Toronto General Hospital — Toronto

Colombia · 1 center

• Hospital Pablo Tobon Uribe — Medellín

Hungary · 1 center

• Semmelweis University/Semmelweis Egyetem — Budapest

Jordan · 1 center

• Jordan University Hospital (JUH) — Amman

Peru · 1 center

• Clinica San Felipe — Lima

Philippines · 1 center

• St Lukes Medical Center — Quezon City

Romania · 1 center

• Prof Dr Ion Chiricuta Cancer Institute — Cluj-Napoca

Singapore · 1 center

• National University Hospital — Singapore

United Kingdom · 1 center

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

Identifiers

NCT: NCT05744921 · R3918-PNH-2050 · 2021-004931-10 · 2023-510336-36-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗