Clinical trial NCT05133531: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: PNH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-24
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Percent change in lactate dehydrogenase (LDH)
timeFrame: From baseline to week 26
measure: Transfusion avoidance
timeFrame: From post-baseline day 1 through week 26
measure: Adequate control of hemolysis
timeFrame: From week 8 through week 26, inclusive
Secondary outcomes:
measure: Maintenance of adequate control of hemolysis
timeFrame: From week 8 through week 26, inclusive
measure: Breakthrough hemolysis
timeFrame: From post-baseline day 1 through week 26
measure: Adequate control of hemolysis
timeFrame: From week 8 through week 26, inclusive
measure: Hemoglobin stabilization
timeFrame: From day 1 (post-baseline) through week 26
measure: Normalization of LDH
timeFrame: Between week 8 through week 26, inclusive
measure: Transfusion avoidance
timeFrame: Day 1 through week 26
measure: Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale
timeFrame: From baseline to week 26
measure: Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
timeFrame: From baseline to week 26
measure: Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30
timeFrame: From baseline to week 26
measure: Percent change in LDH
timeFrame: From baseline to week 26
measure: Rate of RBC transfused
timeFrame: Post-baseline Day 1 through week 26
measure: Number of units of RBC transfused
timeFrame: Post-baseline Day 1 through week 26
measure: Time to first LDH ≤1.5 × ULN
timeFrame: Up to Week 26
measure: Time to first LDH ≤1.0 × ULN
timeFrame: Up to Week 26
measure: Percentage of days with LDH ≤1.5 × ULN
timeFrame: Between week 8 and week 26, inclusive
measure: Change in hemoglobin levels
timeFrame: From baseline to week 26
measure: Incidence and severity of treatment emergent serious adverse events (SAEs)
timeFrame: Up to 26 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
timeFrame: Up to 26 weeks
measure: Incidence and severity of TEAEs leading to treatment discontinuation
timeFrame: Up to 26 weeks
measure: Change in total CH50
timeFrame: From baseline to week 26
measure: Percent change in total CH50
timeFrame: From baseline to week 26
measure: Concentration of total C5 in plasma
timeFrame: Up to 60 weeks
measure: Concentrations of total pozelimab in serum
timeFrame: Up to 60 weeks
measure: Concentrations of cemdisiran in plasma
timeFrame: Up to 60 weeks
measure: Concentrations of total ravulizumab in serum
timeFrame: Up to 34 weeks
measure: Concentrations of total eculizumab in serum
timeFrame: Up to 30 weeks
measure: Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
timeFrame: Up to 60 weeks
measure: Incidence of treatment emergent ADAs to cemdisiran
timeFrame: Up to 60 weeks
Other outcomes:
Locations:
city: Whittier
country: United States
facility: The Oncology Institute of Hope & Innovation
state: California
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
state: Antioquia
city: Thessaloniki
country: Greece
facility: George Papanikolaou Hospital
city: Budapest
country: Hungary
facility: Semmelweis University
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
state: Delhi
city: Kannur
country: India
facility: Malabar Cancer Center, Kerala
state: Kerala
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
state: Kerala
city: Mumbai
country: India
facility: K J Somaiya Super Specialty Hospital & Research Centre
state: Maharashtra
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education & Research (PGIMER)
state: Punjab
city: Lucknow
country: India
facility: King George Hospital
state: Uttar Pradesh
city: Jaipur
country: India
facility: Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
city: Firenze
country: Italy
facility: Aou Careggi
state: Florence
city: Rome
country: Italy
facility: Fondazione Policlinico Universitrio a. Gemelli - IRCCS
city: Turin
country: Italy
facility: Hematology Citta della Salute e della Scienza di Torino
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Ogaki
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Moriguchi
country: Japan
facility: Matsushita Memorial Hospital
state: Osaka
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Amman
country: Jordan
facility: Jordan University Hospital (JUH)
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent Hospital
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Ajou University Medical Center
state: Gyeonggi
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Namdong-Gu
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Pahang
city: Kuantan
country: Malaysia
facility: Hospital Tg Ampuan Afzan
state: Pahang
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
state: Sabah
city: Monterrey
country: Mexico
facility: Servicio de Hematologia del Hospital Universitario de la Uanl
state: Nuevo Leon
city: Lima
country: Peru
facility: Clinica San Felipe
city: Quezon City
country: Philippines
facility: St Lukes Medical Center
state: Central Luzon
city: Gdansk
country: Poland
facility: University Clinical Center Medical University of Gdansk
state: Pomeranian Voivodeship
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr2 Bydgoszcz
city: Warsaw
country: Poland
facility: Institute of Hematology and Transfusion Medicine
city: Cluj-Napoca
country: Romania
facility: Ion Chiricuta Oncology Institute
state: Cluj
city: Craiova
country: Romania
facility: Municipal Hospital Filantropia
state: Dolj
city: Targu Mures
country: Romania
facility: Targu Mures Clinical County Emergency Hospital
state: Mures
city: Singapore
country: Singapore
facility: National University Hospital
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Murcia
country: Spain
facility: Hospital General JM Morales Meseguer
city: Taichung
country: Taiwan
facility: China Medical University Hospital
state: Central Taiwan
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
state: Hunan Province
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: Hualien City
country: Taiwan
facility: Hualien Tzu Chi Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital (VGHTC)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Hat Yai
country: Thailand
facility: Clinical Research Center, Faculty of Medicine, Prince of Songkla University
state: Songkhla
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Chiang Mai
country: Thailand
facility: Chaing Mai University
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Istanbul
country: Turkey
facility: Istanbul University
city: Izmir
country: Turkey
facility: Ege University
city: Leeds
country: United Kingdom
facility: St James Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: