A Study Evaluating the Safety, Pharmacokinetics, and Effi... | NCT04432584

NCT04432584

ID	Type	Description	Link
2020-000597-26	EudraCT Number
2023-506526-37-00	EU Trial (CTIS) Number

Status Module

Name	Class
Chugai Pharmaceutical	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (Crovalimab)	Experimental	Participants will receive a loading series of crovalimab comprised of an intravenous (IV) dose on Day 1, followed by weekly crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.	Drug: Crovalimab
Arm B (Eculizumab)	Active Comparator	Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and every 2 weeks (Q2W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.	Drug: Eculizumab
Arm C (Crovalimab) (Exploratory)	Experimental	Participants with a body weight ≥ 5 to <12 kilograms (kg) will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight ≥ 12 to < 20 kg and ≥ 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight ≥ 12 to < 20 kg and Q4W thereafter, for participants with a body weight > 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Crovalimab	Drug	Dosing depends on body weight. Participants will be dosed as follows: 5 kg to < 12 kg: 100 mg IV on Week 1 Day 1 (W1D1); 85 mg SC on Week 1 Day 2 (W1D2) and Q2W from Week 3 until end of study 12 kg to < 20 kg: 200 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 170 mg SC, Q2W from Week 5 until end of study 20 kg to < 30 kg: 300 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 340 mg SC, Q4W from Week 5 until end of study 30 kg to < 40 kg: 400 mg IV on W1D1; 170 mg SC on W1D2, Weeks 2, 3 and 4; 510 mg SC, Q4W from Week 5 until end of study 40 kg to < 100 kg: 1000 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 680 mg SC, Q4W from Week 5 until end of study 100 kg: 1500 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 1020 mg SC, Q4W from Week 5 until end of study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Adverse Events (AEs) and by Severity	Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).	Up to approximately 6 years
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)		Up to approximately 6 years
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation		Up to approximately 6 years
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		Up to approximately 6 years

Secondary Outcomes

Measure	Description	Time Frame
Serum Concentrations of Crovalimab or Eculizumab Over Time		Up to approximately 6 years
Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation		Baseline

Eligibility Module

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

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Carolinas Healthcare System		Charlotte	North Carolina	28204	United States
Nationwide Children's Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
40978458	Derived	Kulasekararaj AG, Nishimura JI, Roth A, Beveridge L, Buatois S, Buri M, Compagno N, Luder Y, Sreckovic S, Scheinberg P. Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies. Ther Adv Hematol. 2025 Sep 17;16:20406207251359246. doi: 10.1177/20406207251359246. eCollection 2025.
39535306

IPD Sharing Statement Module

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases