A Study Evaluating the Efficacy and Safety of Crovalimab in Adult and Adolescent Patients with atypical Hemolytic Uremic Syndrome (aHUS)

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

1 Jul 2021 → ongoing

Decision date (initial)

2024-03-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505089-27-00

EudraCT number

2020-002475-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Others, Safety, Pharmacokinetic

To evaluate the effect of crovalimab in complement inhibitor treatment-naive (Naive) patients

Secondary objectives 4

1. To evaluate the effect of crovalimab in patients in the Naive and Switch (switching from an existing complement inhibitor treatment to crovalimab) patients
2. To evaluate the overall safety and tolerability of crovalimab
3. To evaluate the pharmacokinetics of crovalimab
4. To evaluate the immune response to crovalimab

Conditions and MedDRA coding

Atypical Hemolytic Uremic Syndrome (aHUS)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

n/a

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment in accordance with current local guidelines or standard of care, as applicable in patients with complement deficiency (for ALL cohorts)
2. Adequate hepatic function, AST and ALT ≤ 3×ULN at the time of screening; no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis (for ALL cohorts)
3. For female patients of childbearing potential, an agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception (for ALL cohorts)
4. Onset of initial TMA presentation, within 28 days prior to the first dose of crovalimab (For naïve cohort only)
5. Clinical evidence of response to either eculizumab or ravulizumab, as documented by a platelet count ≥LLN, LDH ≤ULN, and stable (decrease or increase of ≤20%) or improving creatinine at two consecutive measurements at least 4 weeks apart prior to Week 1 Day 1 of crovalimab treatment. (For switch cohort only)
6. Known C5 polymorphism (e.g., Arg885) (For C5SNP cohort only)

Exclusion criteria 6

1. TMA associated with non-aHUS-related renal disease
2. History of a kidney disease other than aHUS, affecting renal function
3. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome
4. Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration
5. History of Neisseria meningitidis infection within 6 months of study enrollment
6. History of malignancy within 5 years prior to screening and up to the first crovalimab administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Proportion of patients with complete TMA response (cTMAr)

Secondary endpoints 18

1. 1. Dialysis requirement status (yes/no) change
2. 2. Observed value and change from baseline in estimated glomerular filtration rate (eGFR)
3. 3. Proportion of patients with change from baseline in chronic kidney disease stage
4. 4. Observed value and change from baseline in hematologic parameters
5. 5. In adults (≥ 18 years), change from baseline in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire
6. 6. Incidence and severity of adverse events
7. 7. Change in targeted vital signs and clinical laboratory test results
8. 8. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, malignant hypertension, and infections
9. 9. Incidence of adverse events leading to study drug discontinuation
10. 10. Serum concentrations of crovalimab
11. 11. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab
12. 12. Proportion of patients with platelet count ≥ LLN
13. 13. Proportion of patients with normalization of LDH
14. 14. Proportion of patients with ≥ 25% decrease in serum creatinine from baseline
15. 15. Time to cTMAr
16. 16. Duration of cTMAr
17. 17. Proportion of patients with cTMAr
18. 18. Proportion of patients with maintained TMA control (mTMAc)

Investigational products

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

Test 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 13

Locations

7 EU/EEA countries · 23 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 130 files

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

Application history

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