Clinical trial NCT04434092: A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors
Official title: A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously 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: 204
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 non-inferiority of crovalimab compared with eculizumab in participants with PNH who have not been previously treated with complement inhibitor therapy.


Eligibility criteria: Inclusion Criteria:

* Body weight ≥ 40 kg at screening (pediatric participants with body weight \< 40 kg)
* Willingness and ability to comply with all study visits and procedures
* Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
* LDH level ≥ 2x ULN at screening (as per local assessment)
* 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 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:

* Current or previous treatment with a complement inhibitor
* History of allogeneic bone marrow transplantation
* History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration
* 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 is greater
* 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
* Splenectomy \< 6 months before screening
* Positive for Active Hepatitis B and C infection (HBV/HCV)
* History of or ongoing cryoglobulinemia at screening

Primary outcomes:
measure: Percentage of Participants Who Achieve Transfusion Avoidance (TA)
timeFrame: Baseline through Week 25
measure: Percentage of Participants With Hemolysis Control
timeFrame: Week 5 through Week 25
Secondary outcomes:
measure: Percentage of Participants With Breakthrough Hemolysis (BTH)
timeFrame: Baseline through Week 25
measure: Percentage of Participants With Stabilization of Hemoglobin
timeFrame: Baseline through Week 25
measure: Mean Change in Fatigue
timeFrame: Baseline up to Week 25
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to 6 years
measure: Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (Including Meningococcal Meningitis)
timeFrame: Up to 6 years
measure: Percentage of Participants With AEs Leading to Study Drug Discontinuation
timeFrame: Up to 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
timeFrame: Up to 6 years
measure: Serum Concentrations of Crovalimab and Eculizumab Over Time
timeFrame: Up to 6 years
measure: Percentage of Participants With Anti-crovalimab Antibodies
timeFrame: Up to 6 years
measure: Change in Pharmacodynamic (PD) Biomarkers Including Complement Activity (CH50) Over Time
timeFrame: Up to 6 years
measure: Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
timeFrame: Up to 6 years
measure: Observed Value in Reticulocyte Count (count/milliliters [mL])
timeFrame: Up to 6 years
measure: Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
timeFrame: Up to 6 years
measure: Change From Baseline in Reticulocyte Count (count/mL)
timeFrame: Baseline up to Week 25
measure: Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
timeFrame: Baseline up to Week 25
Other outcomes:
Locations:
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion (OMI)
city: Curitiba
country: Brazil
facility: Centro Integrado de Oncologia de Curitiba
state: Paraná
city: Santo Andre
country: Brazil
facility: *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
state: São Paulo
city: São Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hangzhou City
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nantong City
country: China
facility: Affiliated Hospital of Nantong University
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Lille cedex
country: France
facility: Hopital Claude Huriez - CHU Lille
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Essen
country: Germany
facility: Universitaetsklinkm
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki G. Papanikolaou
city: Hokkaido
country: Japan
facility: Sapporo Medical University Hospital
city: Ibaraki
country: Japan
facility: University of Tsukuba Hospital
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinics, Public Institution
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Selangor
city: Ciudad de México
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Global Trial Research Center S.A. de C.V.
state: Nuevo LEON
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Quezon
country: Philippines
facility: St Lukes Medical Center
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr2 im. dr J. Biziela
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
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: Lisboa
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto - Hospital de Santo António
city: Bucuresti
country: Romania
facility: Spitalul Universitar de Urgenta Bucuresti
city: Craiova
country: Romania
facility: Spitalul Clinic Municipal Filantropia Craiova
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Albacete
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
state: LAS Palmas
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Kaohisung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung
city: Taipei
country: Taiwan
facility: National Taiwan Universtiy Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Pathum Wan
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+
state: KIEV Governorate
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: