A study to test how effective belumosudil tablets are for treating adult participants with chronic lung allograft dysfunction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Dec 2023 → ongoing

Decision date (initial)

2023-10-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-503462-23-00

WHO UTN

U1111-1280-6777

ClinicalTrials.gov

NCT06082037

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To demonstrate the efficacy of belumosudil compared with placebo on lung function as measured by forced expiratory volume in 1 second (FEV1) in participants with Stage 1 and 2 CLAD following bilateral lung transplantation

Secondary objectives 6

1. To demonstrate the efficacy of belumosudil compared with placebo on lung function as measured by FEV1 in participants with CLAD following bilateral lung transplantation
2. To evaluate the efficacy of belumosudil on lung function as measured by forced vital capacity (FVC)
3. To evaluate the effects of belumosudil on CLAD progression
4. To evaluate the efficacy of belumosudil on exercise capacity as measured by 6-minute walk test
5. To evaluate the effects of belumosudil on patient-reported outcomes (PROs)
6. To assess the safety of belumosudil in participants with CLAD after bilateral lung transplant

Conditions and MedDRA coding

Lung transplant rejection

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 3

1. Participant ≥1 year post bilateral lung transplantation at the time of screening
2. Participants presenting with CLAD Stage 1 or 2: FEV1 from >50% to 80% of posttransplant baseline at screening and at randomization
3. Participants who have received at least 8 weeks of azithromycin (≥250 mg/day, at least 3 times a week) prior to randomization

Exclusion criteria 2

1. FEV1 ≤50% of the post-transplant baseline value (CLAD 3 and 4)
2. Lung function decline that can be explained by non-CLAD causes including but not limited to acute lung allograft rejection (>A1), antibody-mediated rejection, airway stenosis, or tracheobronchomalacia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline to Week 26 in FEV1

Secondary endpoints 14

1. Response rate at Week 26. Defined as the proportion of participants with ≤10% decline in FEV1 at Week 26 compared with baseline
2. Absolute change from baseline to Week 26 in FEV1
3. Absolute change from baseline to Week 26 in percent predicted FEV1
4. Percent change from baseline to Week 26 in FVC
5. Absolute change from baseline to Week 26 in FVC
6. Absolute change from baseline to Week 26 in percent predicted FVC
7. Time to CLAD progression during the doubleblind treatment period.Defined as the first of the following events: >10% decline in FEV1 compared with baseline, or change in CLAD stage, or re-transplantation, or death.
8. Time to re-transplantation or death
9. Percent change from baseline to Week 26 in 6- minute walk distance
10. Absolute change from baseline to Week 26 in 6-minute walk distance
11. Change from baseline to Week 26 in Saint George Respiratory Questionnaire (SGRQ). Total score and scores by domain
12. Change from baseline to Week 26 in EQ-5D-5L.Visual analogue scale and individual dimensions
13. Change from baseline to Week 26 in Patient- Reported Outcomes Measurement Information System-29 profile version 2.1. PROMIS-29 profile V2.1 (domain scores)
14. Number of participants with adverse events (AEs) and serious adverse events (SAEs). Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), as well as laboratory abnormalities during the double-blind treatment period and the open-label extensions

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

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 15

Locations

14 EU/EEA countries · 31 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 247 files

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

Application history

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