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
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)
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
Patients Entering from the Parent Study
1. 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.
2. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
Patients Entering with C5 polymorphism
1. 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
2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
3. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
4. LDH level ≥2 × upper limit of normal (ULN) at the screening visit
5. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
Key Exclusion Criteria:
Patients Entering from the Parent Study
1. 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
2. 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
1. 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
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. 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
4. Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
5. Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
6. Known hereditary complement deficiency
7. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
8. 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
Primary outcome measure(s)
Incidence of treatment-emergent serious adverse events (SAEs) — Up to week 108 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
Severity of treatment-emergent SAEs — Up to week 108
Incidence of treatment emergent adverse events of special interest (AESIs) — Up to week 108 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
Severity of treatment emergent AESIs — Up to week 108
Incidence of adverse events (AEs) leading to permanent treatment discontinuation — Up to week 108 Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.
Severity of adverse events (AEs) leading to permanent treatment discontinuation — Up to week 108 Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.
Percent change from baseline in lactate dehydrogenase (LDH) — Baseline to week 36
Trial sites (47)
Facility
City
Region
Status
Toronto General Hospital
Toronto
Ontario
Recruiting
Hospital Pablo Tobon Uribe
Medellín
Antioquia
Recruiting
Semmelweis University/Semmelweis Egyetem
Budapest
Hungary
Recruiting
Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
Kochi
Kerala
Recruiting
K J Somaiya Super Specialty Hospital & Research Centre
Mumbai
Maharashtra
Recruiting
Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
New Delhi
National Capital Territory of Delhi
Recruiting
Postgraduate Institute of Medical Education & Research
Chandigarh
India
Recruiting
Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
Jaipur
India
Recruiting
Aou Careggi
Florence
Firenze
Recruiting
SC Hematology, AOU Città della Salute e della Scienza di Torino
Torino
Italy
Recruiting
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
Nagoya
Aichi-ken
Withdrawn
University of Tsukuba Hospital
Tsukuba
Ibaraki
Recruiting
Jordan University Hospital (JUH)
Amman
Jordan
Recruiting
Hospital Tg Ampuan Afzan
Kuantan
Pahang
Recruiting
Hospital Queen Elizabeth
Kota Kinabalu
Sabah
Recruiting
Hospital Ampang
Ampang
Selangor
Recruiting
Clinica San Felipe
Lima
Peru
Recruiting
St Lukes Medical Center
Quezon City
National Capital Region
Recruiting
In-Vivo Sp. z o.o.
Bydgoszcz
Kuyavian-Pomeranian Voivodeship
Recruiting
University Clinical Center Medical University of Gdansk
Gdansk
Pomeranian Voivodeship
Recruiting
Szpital Uniwersytecki Nr2 Bydgoszcz
Bydgoszcz
Poland
Completed
Prof Dr Ion Chiricuta Cancer Institute
Cluj-Napoca
Cluj
Recruiting
National University Hospital
Singapore
Singapore
Recruiting
St. Vincent Hospital
Suwon
Gyeonggi-do
Recruiting
Ajou University Medical Center
Suwon
Gyeonggi-do
Recruiting
Gachon University Gil Medical Center
Incheon
Namdong-Gu
Recruiting
Pusan National University Hospital
Busan
South Korea
Recruiting
Severance Hospital Yonsei University Health System
Seoul
South Korea
Recruiting
Samsung Medical Center
Seoul
South Korea
Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul
South Korea
Recruiting
Ewha Womans University Mokdong Hospital
Seoul
South Korea
Recruiting
Hospital Universitario Basurto
Bilbao
Vizcaya
Recruiting
Hospital Clinic de Barcelona
Barcelona
Spain
Recruiting
China Medical University Hospital
Taichung
Central Taiwan
Recruiting
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan
Hunan Province
Recruiting
Changhua Christian Hospital
Changhua
Taiwan
Recruiting
Hualien Tzu Chi Hospital
Hualien City
Taiwan
Recruiting
Taichung Veterans General Hospital (VGHTC)
Taichung
Taiwan
Recruiting
National Taiwan University Hospital
Taipei
Taiwan
Recruiting
Tri-Service General Hospital
Taipei
Taiwan
Recruiting
+ 7 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.