A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and efficacy of Crovalimab versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated with Complement Inhibitors.

• Register: EUCTR
• Last refreshed on: 8 July 2024
• Main ID: EUCTR2020-000597-26-PL
• Date of registration: 16/09/2020
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche Ltd
• Public title: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and efficacy of Crovalimab versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated with Complement Inhibitors.
• Scientific title: A PHASE III, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED, MULTICENTER STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF CROVALIMAB VERSUS ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) CURRENTLY TREATED WITH COMPLEMENT INHIBITORS
• Date of first enrolment: 23/11/2020
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000597-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Colombia, Czech Republic, Czechia, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Portugal, Spain, Sweden, Taiwan, Thailand, Türkiye, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
General Inclusion Criteria (All Patients)
- Body weight >= 40 kg
- Documented diagnosis of PNH, confirmed by high sensitivity flow
cytometry evaluation of WBCs,
- 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. Vaccination currency should be maintained throughout
the study in accordance with most current local guidelines or standardof-
care as applicable in patients with complement deficiency
- Vaccination against Haemophilus influenzae type B and Streptococcus
pneumoniae according to national vaccination recommendations
- Platelet count >= 30,000/mm*3 at screening without transfusion
support within 7 days of lab testing.
- ANC > 500/micro L at screening
- For female patients of childbearing potential: agreement to remain abstinent or use contraception
For Patients in Randomized Arms (Arm A and B)
- Age >= 18 years
- Documented treatment with eculizumab according to the approved
dosing recommended for PNH and completion of a minimum of 24 weeks
of treatment prior to Day 1
- Lactate dehydrogenase (LDH) <= 1.5 × ULN at screening
For Patients in Non Randomized Arm (Arm C)
- Age <18 old, currently treated with eculizumab OR
- Currently treated with ravulizumab OR
- Currently treated with eculizumab at higher-than-approved doses OR
- Patients with known C5 polymorphism and poorly controlled hemolysis by eculizumab or ravulizumab
- Adult patients currently treated with approved doses of eculizumab LDH <= 1.5 × ULN at screening

Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 152
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion criteria:
- Major Adverse Vascular Event within 6 months prior to first drug
administration (Day 1)
- History of allogeneic bone marrow transplantation,
- 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 or within 46 weeks (approximately 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)
- 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 patient, or would, in the
opinion of the Investigator, preclude the patient's safe participation in
and completion of the study
- Splenectomy <= 6 months prior to screening
- Positive for hepatitis B surface antigen at screening
- Positive for hepatitis C virus antibody at screening confirmed by
detectable HCV RNA
- History of or ongoing cryoglobulinemia at screening



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: Crovalimab
Product Code: RO7112689/F03-01
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: CROVALIMAB
Current Sponsor code: RO7112689
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 170-

Trade Name: Soliris
Product Name: Eculizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Crovalimab
Product Code: RO7112689/F03-10
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: CROVALIMAB
Current Sponsor code: RO7112689
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 170-

Primary Outcome(s)

Secondary Objective: • To characterize the crovalimab, eculizumab, and ravulizumab pharmacokinetics profile
• To evaluate the immune response to crovalimab
• To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab, eculizumab, and ravulizumab activity
• To evaluate the efficacy of crovalimab compared with eculizumab

Main Objective: To evaluate the safety and tolerability of crovalimab compared with eculizumab

Primary end point(s): 1. Incidence and severity of adverse events
2. Change from baseline in targeted vital signs
3. Change from baseline in targeted clinical laboratory test results
4. Incidence and severity of injection-site reactions, infusion-related
reactions, hypersensitivity, and infections
5. Incidence of adverse events leading to study drug discontinuation
6. Incidence and severity of clinical manifestations of drug-target-drug
complex formation in patients who switched to crovalimab treatment
from eculizumab or ravulizumab treatment

Timepoint(s) of evaluation of this end point: 1. Up to 8 years
2-3. From baseline to 8 years
4-5. Up to 8 years
6. From baseline to 8 years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to 8 years (crovalimab) and up to Week 25 (eculizumab)
2. At baseline
3. At baseline (prevalence) and up to 8 years (incidence)
4-6. Up to 8 years
7. From Baseline to Weeks 21, 23, 25
8-11. From Baseline to Week 25

Secondary end point(s): 1. Serum concentration of crovalimab or eculizumab
2. Serum concentration of ravulizumab
3. Prevalence and incidence of anti-drug antibodies (ADAs) to
crovalimab
4. Change over time in pharmacodynamic biomarkers
5. Change over time in free C5 concentration in crovalimab-treated
patients
6. Observed value and absolute change in parameters reflecting
hemolysis
7. Percent change from baseline in LDH level averaged over Weeks 21,
23, and 25 LDH measurements
8. Proportion of patients with transfusion avoidance
9. Proportion of patients with breakthrough hemolysis
10. Proportion of patients with stabilization of hemoglobin
11. Mean change in fatigue as assessed through use of the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale

Secondary ID(s)

2020-000597-26-SE

BO42161

Source(s) of Monetary Support

F.Hoffman-La Roche Ltd

Chugai Pharmaceutical Co. Ltd

Ethics review

Status: Approved
Approval date: 29/09/2020
Contact: