A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)

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

Gender

Male and Female

Therapeutic area

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

Trial duration

6 Dec 2021 → 9 Apr 2026

Decision date (initial)

2023-07-20

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

2022-502542-28-00

EudraCT number

2020-004839-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Safety

To evaluate the efficacy of crovalimab compared with placebo

Secondary objectives 4

1. To evaluate the efficacy of crovalimab compared with placebo
2. To evaluate the safety and tolerability of crovalimab compared with placebo
3. To evaluate the pharmacokinetics of crovalimab
4. To evaluate the immune response to crovalimab

Conditions and MedDRA coding

Sickle Cell Disease

Regulatory references

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
2. Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia)
3. Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomisation
4. If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons
5. Vaccination against N. meningitides serotypes A, C, W, and Y, and vaccinations against H. influenza type B and S. pneumonia
6. Adequate hepatic and renal function

Exclusion criteria 6

1. History of hematopoietic stem cell transplant
2. Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study
3. History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment
4. Hemoglobin <6 g/dL
5. Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration
6. Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of medical facility VOEs (AVR)

Secondary endpoints 11

1. Annualized rate of home VOE captured by patient report on a handheld device at home
2. Annualized rate of uncomplicated medical facility VOE
3. Annualized rate of acute chest syndrome (ACS)
4. Annualized rate of days hospitalized for medical facility VOE
5. Annualized rate of days hospitalized for treatment of non-VOE complications of SCD
6. Change in hematologic measures from baseline to Week 49
7. Time to first medical facility VOE from randomization
8. Change in urinary albumin-creatinine ratio from baseline to Week 49
9. Change from baseline to Week 49 in tricuspid regurgitant jet velocity (TRV)
10. Proportion of patients with TRV > 2.5 m/s at Week 49
11. Change from baseline to Week 49 in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults

Investigational products

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

Test 1

Placebo 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

Head of CTRM Clinical Trial Regulatory Management, Product Development Regulatory

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Head of CTRM Clinical Trial Regulatory Management, Product Development Regulatory

Third parties 10

Locations

4 EU/EEA countries · 8 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 45 files

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

Application history

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