A study to test an oral medicine, belumosudil, in combination with corticosteroids in participants at least 12 years of age with newly diagnosed chronic graft versus host disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Research & Development

Participant type

Pediatric, Patients

Age range

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

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Feb 2025 → ongoing

Decision date (initial)

2024-02-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-505394-32-00

WHO UTN

U1111-1280-4918

ClinicalTrials.gov

NCT06143891

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

• Demonstrate the superiority of belumosudil in combination with prednisone vs placebo in combination with prednisone in Event-Free Survival (EFS)

Secondary objectives 13

1. Demonstrate the superiority of belumosudil in combination with prednisone vs prednisone alone in modified Lee Symptom Scale (mLSS) improvement
2. Demonstrate the superiority of belumosudil in combination with prednisone vs prednisone alone in durable overall response rate (ORR)
3. Demonstrate the superiority of belumosudil in combination with prednisone vs prednisone alone in the rate of corticosteroid withdrawal
4. Overall response rate (ORR)
5. ORR by 24 weeks
6. Duration of response (DOR)
7. Dose reduction in corticosteroids
8. Failure Free Survival (FFS)
9. Change in patient reported outcome (PRO)
10. Safety
11. Overall survival
12. Time to response (TTR)
13. Response by organ

Conditions and MedDRA coding

chronic graft versus host disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients must be at least 12 years of age inclusive, at the time of signing the informed consent
2. Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014)
3. Participants who require systemic treatment with corticosteroids for cGVHD
4. Participants who have not received any prior systemic treatment for cGVHD (including ECP)
5. If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol
6. For adult participants, the body weight should be ≥40 kg. For adolescent participants, the body weight should be ≥30 kg.
7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. Participants or their legally authorized representative must be capable of giving signed informed consent

Exclusion criteria 22

1. Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator’s judgement
2. Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
3. Post-transplant lymphoproliferative disease within 4 weeks prior to randomization
4. Unable to swallow tablets
5. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
6. Female participants who are pregnant or breastfeeding
7. Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day
8. Participant has had previous exposure to belumosudil.
9. Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant.
10. Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer
11. - Absolute neutrophil count (ANC) <0.5 x 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening
12. Karnofsky (if aged ≥16 years)/Lansky (if aged <16 years) Performance Score of < 60
13. - Platelets <25 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
14. Any active, uncontrolled infections assessed to be clinically significant by the Investigator
15. Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged <18 years)
16. - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN without liver cGVHD or>5 × ULN with liver) cGVHD
17. Total bilirubin >1.5 × (ULN) (>3 × ULN if Gilbert syndrome)
18. Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014)
19. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease)
20. Known history of human immunodeficiency virus (HIV)
21. Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV)
22. - Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of progressive or relapsed underlying disease after the most recent allogeneic HCT

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival (EFS) from the date of randomization to the date of any predefined event, whichever occurs first

Secondary endpoints 13

1. Proportion of participants who achieve a clinically relevant reduction in mLSS of at least 6 points from baseline (Only in participants at least 18 years of age)
2. Proportion of participants who achieve an overall response (PR or CR) as per 2014 NIH consensus response criteria by 48 weeks and maintained the response for a duration of at least 6 months
3. Proportion of participants who successfully discontinue all systemic corticosteroids for cGVHD for at least 30 days before the occurrence of cGVHD progression, or start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or unacceptable toxicity
4. Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHD
5. Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHD
6. Time from the date of the first response to the date of cGVHD progression, start of new systemic treatment for cGVHD, or death, whichever occurs first. DOR is determined only for participants who achieved overall response (PR or CR) as per 2014 NIH consensus response criteria
7. Proportion of participants with a reduction in daily corticosteroid dose
8. Failure Free Survival (FFS) is defined as the time from the date of randomization to the date of start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first.
9. Change from baseline in Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) (Only in participants at least 18 years of age) and the European Quality of Life Group Questionnaire with 5 Dimensions and 5 Levels (EQ5D5L)
10. Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
11. The time from the date of randomization to the date of death due to any cause
12. Time to Response is defined as the time from randomization to the date the patient has first response (CR or PR).
13. Proportion of participants who achieve CR or PR as per NIH consensus response criteria (2014) at any time point in each involved organ and before the start of a new systemic therapy for cGVHD.

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Research & Development

Sponsor organisation

Sanofi-Aventis Research & Development

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 13

Locations

13 EU/EEA countries · 70 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 13 · Art. 38 CTR

Results and documents

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

Documents 167 files

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

Application history

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