A Study to Evaluate the Efficacy and Safety of Crovalimab versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) not previously Treated with Complement Inhibitors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

8 Apr 2021 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-506498-36-00

EudraCT number

2019-004931-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacokinetic

To evaluate the efficacy of crovalimab compared to eculizumab based on the non-inferiority assessment of the following co-primary endpoints

Secondary objectives 5

1. To evaluate the efficacy of crovalimab compared to eculizumab based on the non-inferiority assessment of the following assessment of the secondary and exploratory efficacy endpoints
2. To evaluate the overall safety and tolerability of crovalimab compared to eculizumab
3. To evaluate the pharmacokinetics of crovalimab and eculizumab
4. To evaluate the immune response to crovalimab
5. To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab and eculizumab activity

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002709-PIP01-19

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Body weight ≥ 40 kg (pediatric patients with body weight < 40 kg)
2. Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs
3. LDH level ≥2 x ULN at screening (as per local assessment)
4. Platelet count >= 30,000/mm*3 at screening without transfusion support within 7 days of lab testing
5. ANC > 500/micro L at screening
6. For female patients of childbearing potential: agreement to remain abstinent or use contraception

Exclusion criteria 6

1. Current or previous treatment with a complement inhibitor
2. History of allogeneic bone marrow transplantation
3. History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration
4. History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high
5. Splenectomy <= 6 months prior to screening
6. History of or ongoing cryoglobulinemia at screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Proportion of patients who achieve transfusion avoidance
2. 2. Proportion of patients with hemolysis control, measured by LDH <=1.5×ULN

Secondary endpoints 14

1. 1. Proportion of patients with breakthrough hemolysis
2. 2. Proportion of patients with stabilization of hemoglobin
3. 3. Mean change in fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue
4. 4. Incidence and severity of adverse events
5. 5. Change from baseline in targeted vital signs
6. 6. Change from baseline in targeted clinical laboratory test results
7. 7. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections
8. 8. Incidence of adverse events leading to study drug discontinuation
9. 9. Incidence and severity of clinical manifestations of drug-target-drug complex formation in patients who switched to crovalimab treatment from eculizumab treatment
10. 10. Serum concentration of crovalimab and eculizumab
11. 11. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab
12. 12. Change over time in pharmacodynamic biomarkers
13. 13. Change over time in free C5 concentration in crovalimab-treated patients
14. 14. Observed value and absolute change from baseline to week 25 in parameters reflecting hemolysis

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 14

Locations

9 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 97 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications