Clinical trial NCT06082037: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Transplant Rejection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-10-13
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Percent change from baseline to Week 26 in forced expiratory volume in 1 second (FEV1)
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Response rate at Week 26
timeFrame: Baseline to Week 26
measure: Absolute change from baseline to Week 26 in FEV1
timeFrame: Baseline to Week 26
measure: Absolute change from baseline to Week 26 in percent predicted FEV1
timeFrame: Baseline to Week 26
measure: Percent change from baseline to Week 26 in forced vital capacity (FVC)
timeFrame: Baseline to Week 26
measure: Absolute change from baseline to Week 26 in FVC
timeFrame: Baseline to Week 26
measure: Absolute change from baseline to Week 26 in percent predicted FVC
timeFrame: Baseline to Week 26
measure: Time to CLAD progression during the double-blind treatment period
timeFrame: Baseline to Week 26
measure: Time to re-transplantation or death
timeFrame: Up to 7 days after the administration of last dose of study drug
measure: Percent change from baseline to Week 26 in 6-minute walk distance
timeFrame: Baseline to Week 26
measure: Absolute change from baseline to Week 26 in 6-minute walk distance
timeFrame: Baseline to Week 26
measure: Change from baseline to Week 26 in Saint George Respiratory Questionnaire (SGRQ)
timeFrame: Baseline to Week 26
measure: Change from baseline to Week 26 in EQ-5D-5L
timeFrame: Baseline to Week 26
measure: Change from baseline to Week 26 in Patient-Reported Outcomes Measurement Information System-29 profile version 2.1
timeFrame: Baseline to Week 26
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 7 days after the administration of last dose of study drug
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham- Site Number : 8400026
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center- Site Number : 8400019
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center- Site Number : 8400020
state: California
city: Stanford
country: United States
facility: Stanford Hospital- Site Number : 8400008
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital Jacksonville- Site Number : 8400031
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital- Site Number : 8400030
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando- Site Number : 8400023
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital - Tampa - General Circle- Site Number : 8400015
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital- Site Number : 8400027
state: Georgia
city: Chicago
country: United States
facility: Northwestern University- Site Number : 8400003
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center- Site Number : 8400025
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa- Site Number : 8400032
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland School of Medicine - Baltimore- Site Number : 8400009
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital- Site Number : 8400034
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston/Brigham & Women's Hospital (CHB/BWH) - Adult Cystic Fibrosis Program- Site Number : 8400016
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System - Ann Arbor- Site Number : 8400014
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health- Site Number : 8400010
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus- Site Number : 8400036
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center- Site Number : 8400001
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai- Site Number : 8400037
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center- Site Number : 8400002
state: New York
city: Durham
country: United States
facility: Duke University Medical Center- Site Number : 8400017
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Cleveland- Site Number : 8400005
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University- Site Number : 8400028
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System- Site Number : 8400006
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital- Site Number : 8400007
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center- Site Number : 8400018
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center- Site Number : 8400011
state: Texas
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center- Site Number : 8400013
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine- Site Number : 8400024
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital- Site Number : 8400021
state: Texas
city: San Antonio
country: United States
facility: University Health System - San Antonio- Site Number : 8400035
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital- Site Number : 8400004
state: Virginia
city: Sydney
country: Australia
facility: Investigational Site Number : 0360003
state: New South Wales
city: Brisbane
country: Australia
facility: Investigational Site Number : 0360001
state: Queensland
city: Murdoch
country: Australia
facility: Investigational Site Number : 0360002
state: Western Australia
city: Vienna
country: Austria
facility: Investigational Site Number : 0400001
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Yvoir
country: Belgium
facility: Investigational Site Number : 0560002
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240002
state: Alberta
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240001
state: British Columbia
city: Toronto
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Beijing
country: China
facility: Investigational Site Number : 1560004
city: Chengdu
country: China
facility: Investigational Site Number : 1560002
city: Fuzhou
country: China
facility: Investigational Site Number : 1560008
city: Guangzhou
country: China
facility: Investigational Site Number : 1560007
city: Hangzhou
country: China
facility: Investigational Site Number : 1560001
city: Hefei
country: China
facility: Investigational Site Number : 1560005
city: Wuxi
country: China
facility: Investigational Site Number : 1560003
city: Zhengzhou
country: China
facility: Investigational Site Number : 1560006
city: Olomouc
country: Czechia
facility: Investigational Site Number : 2030002
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460001
city: Le Plessis-robinson
country: France
facility: Investigational Site Number : 2500005
city: Marseille
country: France
facility: Investigational Site Number : 2500006
city: Paris
country: France
facility: Investigational Site Number : 2500004
city: Pessac
country: France
facility: Investigational Site Number : 2500002
city: Saint-herblain
country: France
facility: Investigational Site Number : 2500003
city: Suresnes
country: France
facility: Investigational Site Number : 2500001
city: Munich
country: Germany
facility: Investigational Site Number : 2760003
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480001
city: Petah Tikva
country: Israel
facility: Investigational Site Number : 3760001
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano-Site Number : 3800001
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo-Site Number : 3800003
state: Lombardia
city: Palermo
country: Italy
facility: IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione)-Site Number : 3800004
state: Sicilia
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese UOC Malattie Respiratorie e Trapianto Polmonare-Site Number : 3800002
state: Toscana
city: Yangsan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Groningen
country: Netherlands
facility: Investigational Site Number : 5280001
city: Oslo
country: Norway
facility: Investigational Site Number : 5780001
city: A Coruña
country: Spain
facility: Investigational Site Number : 7240002
state: A Coruña [La Coruña]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Investigational Site Number : 7240001
state: Cantabria
city: Valencia
country: Spain
facility: Investigational Site Number : 7240004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: