A Study to Test How Effective Belumosudil Tablets Are for Treating Adult Participants With Chronic Lung Allograft Dysfunction

Official title

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study, Followed by Open-label Extensions, to Evaluate the Efficacy of Oral Belumosudil in Adult Participants With Chronic Lung Allograft Dysfunction (CLAD) Following Bilateral Lung Transplantation

Overview

This double-blind, randomized, placebo-controlled, multinational, multicenter, parallel-group, Phase 3, 2-arm, study will investigate the efficacy and safety of belumosudil compared with placebo, both administered on top of azithromycin and standard-of-care regimen of immunosuppression in male or female participants at least 1 year after bilateral lung transplant, who are at least 18 years of age and who have evidence of progressive CLAD despite azithromycin therapy. Study details include: The study duration will be up to 31 weeks for participants not entering the open-label extension (OLE) period and up to 57 weeks for participants entering the OLE period but not the long-term OLE. The treatment duration will be up to 26 weeks for participants not entering the OLE period and up to 52 weeks for participants entering the OLE period but not the long-term OLE. The number of visits will be up to 10 visits for participants not entering the OLE period and up to 16 visits for participants entering the OLE period but not the long-term OLE. For participants who enter the long-term OLE, treatment and study participation will continue with visits every 12 weeks per protocol specifications.

Interventions

• Drug Belumosudil
  Tablet, Oral
• Drug Azithromycin
  Depends on pharmaceutical presentation, Oral
• Drug Placebo
  Tablet, Oral

Primary outcome measures

• Percent change from baseline to Week 26 in forced expiratory volume in 1 second (FEV1) [Time frame: Baseline to Week 26]

Secondary outcome measures (12)

• Response rate at Week 26 [Time frame: Baseline to Week 26]
• Absolute change from baseline to Week 26 in FEV1 [Time frame: Baseline to Week 26]
• Absolute change from baseline to Week 26 in percent predicted FEV1 [Time frame: Baseline to Week 26]
• Percent change from baseline to Week 26 in forced vital capacity (FVC) [Time frame: Baseline to Week 26]
• Absolute change from baseline to Week 26 in FVC [Time frame: Baseline to Week 26]
• Absolute change from baseline to Week 26 in percent predicted FVC [Time frame: Baseline to Week 26]
• Time to CLAD progression during the double-blind treatment period [Time frame: Baseline to Week 26]
• Time to re-transplantation or death [Time frame: Up to 7 days after the administration of last dose of study drug]
• Percent change from baseline to Week 26 in 6-minute walk distance [Time frame: Baseline to Week 26]
• Absolute change from baseline to Week 26 in 6-minute walk distance [Time frame: Baseline to Week 26]
• Change from baseline to Week 26 in Saint George Respiratory Questionnaire (SGRQ) [Time frame: Baseline to Week 26]
• Change from baseline to Week 26 in EQ-5D-5L [Time frame: Baseline to Week 26]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• FEV1 ≤50% of the post-transplant baseline value (CLAD 3 and 4)
• 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 32 centers

• University of Alabama at Birmingham- Site Number : 8400026 — Birmingham
• St. Joseph's Hospital and Medical Center- Site Number : 8400019 — Phoenix
• University of California Los Angeles Medical Center- Site Number : 8400020 — Los Angeles
• Stanford University Medical Center- Site Number : 8400008 — Stanford
• Mayo Clinic in Florida- Site Number : 8400031 — Jacksonville
• Jackson Memorial Hospital- Site Number : 8400030 — Miami
• AdventHealth Orlando- Site Number : 8400023 — Orlando
• Tampa General Hospital - Tampa - General Circle- Site Number : 8400015 — Tampa
• … and 24 more centers

China · 9 centers

• Investigational Site Number : 1560004 — Beijing
• Investigational Site Number : 1560002 — Chengdu
• Investigational Site Number : 1560008 — Fuzhou
• Investigational Site Number : 1560007 — Guangzhou
• Investigational Site Number : 1560001 — Hangzhou
• Investigational Site Number : 1560005 — Hefei
• Investigational Site Number : 1560009 — Shanghai
• Investigational Site Number : 1560003 — Wuxi
• … and 1 more center

France · 6 centers

• Investigational Site Number : 2500005 — Le Plessis-Robinson
• Investigational Site Number : 2500006 — Marseille
• Investigational Site Number : 2500004 — Paris
• Investigational Site Number : 2500002 — Pessac
• Investigational Site Number : 2500003 — Saint-Herblain
• Investigational Site Number : 2500001 — Suresnes

Italy · 5 centers

• Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano-Site Number : 3800001 — Milan
• Investigational Site Number : 3800005 — Padua
• IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione)-Si — Palermo
• Fondazione IRCCS Policlinico San Matteo-Site Number : 3800003 — Pavia
• Azienda Ospedaliera Universitaria Senese UOC Malattie Respiratorie e Trapianto Polmonare-S — Siena

South Korea · 4 centers

• Investigational Site Number : 4100004 — Yangsan
• Investigational Site Number : 4100002 — Seoul
• Investigational Site Number : 4100001 — Seoul
• Investigational Site Number : 4100003 — Seoul

Spain · 4 centers

• Investigational Site Number : 7240002 — A Coruña
• Investigational Site Number : 7240003 — Barcelona
• Investigational Site Number : 7240001 — Santander
• Investigational Site Number : 7240004 — Valencia

Australia · 3 centers

• Investigational Site Number : 0360003 — Darlinghurst
• Investigational Site Number : 0360001 — Brisbane
• Investigational Site Number : 0360002 — Murdoch

Canada · 3 centers

• Investigational Site Number : 1240002 — Edmonton
• Investigational Site Number : 1240001 — Vancouver
• Investigational Site Number : 1240004 — Toronto

Belgium · 2 centers

• Investigational Site Number : 0560001 — Leuven
• Investigational Site Number : 0560002 — Yvoir

Czechia · 2 centers

• Investigational Site Number : 2030002 — Olomouc
• Investigational Site Number : 2030001 — Prague

Austria · 1 center

• Investigational Site Number : 0400001 — Vienna

Denmark · 1 center

• Investigational Site Number : 2080001 — Copenhagen

Finland · 1 center

• Investigational Site Number : 2460001 — Helsinki

Germany · 1 center

• Investigational Site Number : 2760003 — Munich

Hungary · 1 center

• Investigational Site Number : 3480001 — Budapest

Israel · 1 center

• Investigational Site Number : 3760001 — Petah Tikva

Japan · 1 center

• Investigational Site Number : 3920001 — Tokyo

Netherlands · 1 center

• Investigational Site Number : 5280001 — Groningen

Sweden · 1 center

• Investigational Site Number : 7520001 — Gothenburg

Identifiers

NCT: NCT06082037 · EFC17801 · U1111-1280-6777 · 2023-503462-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗