Clinical trial NCT04432584: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
Official title: A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2020-06-16
Enrollment: 190
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.


Eligibility criteria: Inclusion Criteria:

* Body weight ≥ 40 kg at screening (pediatric participants with body weight \< 40 kg)
* Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1
* Lactate Dehydrogenase Levels ≤ 2x the upper limit of normal (ULN) at screening
* Willingness and ability to comply with all study visits and procedures
* Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
* Vaccination against Neisseria meningitidis serotypes A, C, W, and Y \< 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration
* Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label)

Exclusion Criteria:

* History of allogeneic bone marrow transplantation
* History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high
* Pregnant or breastfeeding, or intending to become pregnant during the study, within 10.5 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label)
* Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment
* Positive for Active Hepatitis B and C infection (HBV/HCV)
* Concurrent disease, treatment, procedure, or surgery or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study
* History of or ongoing cryoglobulinemia at screening

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and by Severity
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Clinical Manifestations of Drug-target-drug Complex (DTDC) Formation Amongst Those Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment or Ravulizumab Treatment
timeFrame: Up to approximately 6 years
Secondary outcomes:
measure: Serum Concentrations of Crovalimab or Eculizumab Over Time
timeFrame: Up to approximately 6 years
measure: Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation
timeFrame: Baseline
measure: Percentage of Participants With Anti-crovalimab Antibodies
timeFrame: Up to approximately 6 years
measure: Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time
timeFrame: Up to approximately 6 years
measure: Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
timeFrame: Up to approximately 6 years
measure: Observed Value in Reticulocyte Count (count/milliliters [mL])
timeFrame: Up to approximately 6 years
measure: Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
timeFrame: Up to approximately 6 years
measure: Absolute Change From Baseline in Reticulocyte Count (count/mL)
timeFrame: Baseline up to Week 25
measure: Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
timeFrame: Baseline up to Week 25
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Roeselare
country: Belgium
facility: AZ Delta Campus Westlaan
city: Yvoir
country: Belgium
facility: CHU UCL Namur / site Godinne
city: Taguatinga
country: Brazil
facility: Chronos Pesquisa Clinica
state: Distrito Federal
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre X
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Instituto Joinvilense de Hematologia E Oncologia
state: Santa Catarina
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clínicas FMRP-USP
state: São Paulo
city: Santo Andre
country: Brazil
facility: *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sírio-Libanês
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano
state: São Paulo
city: São Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
city: Levis
country: Canada
facility: CISSS Chaudière-Appalaches
state: Quebec
city: Praha
country: Czechia
facility: Ustav hematologie a krevni transfuze
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Lille cedex
country: France
facility: Hopital Claude Huriez - CHU Lille
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen AOeR
city: Riesa
country: Germany
facility: ELBLANDKLINIKUM Riesa
city: Athens
country: Greece
facility: General Hospital of Athens LAIKO
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Dublin
country: Ireland
facility: St James's Hospital
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale- Ravenna
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Hyogo
country: Japan
facility: Tokushukai Takasago Seibu Hospital
city: Ishikawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Mie
country: Japan
facility: Mie University Hospital
city: Nagano
country: Japan
facility: Japanese Red Cross Society Suwa Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nagasaki
country: Japan
facility: Sasebo City General Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Oshu
country: Japan
facility: Iwate Prefectural Isawa Hospital
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Toyama
country: Japan
facility: Toyama Prefectual Central Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr2 im. dr J. Biziela
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
city: Skórzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Warszawa
country: Poland
facility: MTZ Clinical Research Powered by Pratia
city: Aveiro
country: Portugal
facility: Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Singapore
country: Singapore
facility: National University Hospital
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago.
state: LA Coruna
city: Asturias
country: Spain
facility: Hospital U. Central de Asturias
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Toledo
country: Spain
facility: Complejo Hospitalario de Toledo
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Chang Hua
country: Taiwan
facility: Changhua Christian Hospital
city: Hualien
country: Taiwan
facility: Hualien Tzu Chi Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Universtiy Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty; Neurology
city: Gaziantep
country: Turkey
facility: Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty; Neurology
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital, Hematology Department
city: Izmir
country: Turkey
facility: Ege University Medical Faculty; Hematology
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
city: London
country: United Kingdom
facility: King'S College Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: