Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients
NCT Number: NCT06476132
Acronym: CLAD
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Lung Transplant
Interventions: DRUG: Belumosudil|DRUG: Placebo for Belumosudil
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 234
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-15
Completion Date: 2027-06-30
Locations: University of California, Los Angeles (Site #: 71123), Los Angeles, California, 90095, United States|Johns Hopkins (Site #: 71119), Baltimore, Maryland, 21287, United States|St. Louis Children's Hospital of Washington University (Site #: 71006), Saint Louis, Missouri, 63110, United States|Duke University (Site #: 71139), Durham, North Carolina, 27710, United States|Cincinnati Children's Hospital Medical Center (Site #: 71017), Cincinnati, Ohio, 45229, United States|Cleveland Clinic (Site #: 71101), Cleveland, Ohio, 44195, United States|University of Pennsylvania (Site #: 71111), Philadelphia, Pennsylvania, 19104, United States|University Health Network/Toronto General Hospital (Site #: 71121), Toronto, Ontario, M5G 2N2, Canada

Summary:
The purpose of this study is to see if taking the study drug, Belumosudil, for 52 weeks in addition to your usual care and medication, will prevent Chronic Lung Allograft Dysfunction (CLAD) in participants who have a lung biopsy that shows evidence of rejection or inflammation to the transplanted lung(s). For this study, biopsies that show evidence of Acute Rejection (AR), Lymphocytic Bronchiolitis (LB), Organizing Pneumonia (OP) or Acute Lung Injury (ALI) are referred to as "Qualifying Biopsies"; patients who had evidence of one or more of these conditions on a recent biopsy are eligible for enrollment in this study. Belumosudil is an investigational drug that blocks a molecule in the body that reduces inflammation and scarring and may play a role in the development and progression of CLAD. Belumosudil is a drug approved by the FDA to treat adults and children 12 years and older with chronic graft-versus-host disease (cGVHD), a condition with some similarities to CLAD.

The primary objective it to determine the efficacy of treatment with Belumosudil + maintenance immunosuppression (IS) versus placebo + maintenance IS on preventing the subsequent development of probable or definite CLAD, lung retransplant, or death.

Primary Outcome Measures: Time from randomization to the first occurrence of probable or definite CLAD (per ISHLT 2019 standard defined criteria), lung retransplant, or death, Probable CLAD is defined as a \>= 20% decline in Forced Expiratory Volume in 1 Second (FEV1) compared to the baseline value on 2 measurements taken at least 3 weeks apart and after exclusion or adequate treatment of potential secondary causes of allograft dysfunction.

The baseline FEV1 value is defined as the average of the 2 best posttransplant FEV1s taken at least 3 weeks apart, From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years
Secondary Outcome Measures: Time from randomization to first occurrence of probable or definite CLAD (per ISHLT 2019 standard defined criteria) or lung retransplant, Definite CLAD is a sustained decline in pulmonary function as defined by a persistent decline in lung function meeting the definition of probable CLAD but sustained for a duration of at least 3 months, From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years|Time from randomization to death, From date of randomization until the date of death, through study completion; participants are scheduled to be assessed for a minimum of 1 year up to a maximum of 3 years|Time from randomization to first occurrence of the specific CLAD phenotypes of Restrictive Allograft Syndrome (RAS), Bronchiolitis Obliterans Syndrome (BOS), mixed, or undefined, From date of randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years|Frequency of Acute Rejection (AR), Number of AR events occurring from date of randomization until date of end of treatment visit, an average of 1 year|Frequency of Lymphocytic Bronchiolitis (LB), Number of LB events occurring from date of randomization until date of end of treatment visit, an average of 1 year.|Frequency of Organizing Pneumonia (OP), Number of OP events occurring from date of randomization until date of end of treatment visit, an average of 1 year.|Frequency of Acute Lung Injury (ALI), Number of ALI events occurring from date of randomization until date of end of treatment visit, an average of 1 year.