Lung Transplant Rejection
Conditions
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.
Interventions
DRUGBelumosudil
Tablet, Oral
DRUGAzithromycin
Depends on pharmaceutical presentation, Oral
DRUGPlacebo
Tablet, Oral
Sponsors
Sanofi
Meiji Seika Pharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change from baseline to Week 26 in forced expiratory volume in 1 second (FEV1) | Baseline to Week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate at Week 26 | Baseline to Week 26 | Defined as the proportion of participants with ≤10% decline in FEV1 at Week 26 compared with baseline |
| Absolute change from baseline to Week 26 in FEV1 | Baseline to Week 26 | — |
| Absolute change from baseline to Week 26 in percent predicted FEV1 | Baseline to Week 26 | — |
| Percent change from baseline to Week 26 in forced vital capacity (FVC) | Baseline to Week 26 | — |
| Absolute change from baseline to Week 26 in FVC | Baseline to Week 26 | — |
| Absolute change from baseline to Week 26 in percent predicted FVC | Baseline to Week 26 | — |
| Time to CLAD progression during the double-blind treatment period | Baseline to Week 26 | 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 |
| Time to re-transplantation or death | 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 | Baseline to Week 26 | — |
| Absolute change from baseline to Week 26 in 6-minute walk distance | Baseline to Week 26 | — |
| Change from baseline to Week 26 in Saint George Respiratory Questionnaire (SGRQ) | Baseline to Week 26 | Total score and scores by domain |
| Change from baseline to Week 26 in EQ-5D-5L | Baseline to Week 26 | Visual analogue scale and individual dimensions |
| Change from baseline to Week 26 in Patient-Reported Outcomes Measurement Information System-29 profile version 2.1 | Baseline to Week 26 | Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) profile V2.1 (domain scores) |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Up to 7 days after the administration of last dose of study drug | 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 |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, Norway, South Korea, Spain, Sweden, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free number for US & Canada)
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed