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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
234
Participants will receive Belumosudil 200 mg daily (increased to 200 mg twice daily in participants receiving concurrent strong CYP3A inducers or PPIs) + maintenance IS for a duration of one year from randomization.
Participants will receive Placebo for Belumosudil 200 mg daily (increased to 200 mg twice daily in participants receiving concurrent strong CYP3A inducers or PPIs) + maintenance IS for a duration of one year from randomization.
University of California, Los Angeles (Site #: 71123)
Los Angeles, California, United States
RECRUITINGJohns Hopkins (Site #: 71119)
Baltimore, Maryland, United States
RECRUITINGUniversity of Minnesota (Site 71151)
Minneapolis, Minnesota, United States
RECRUITINGWashington University (Site #: 71157)
St Louis, Missouri, United States
RECRUITINGNYU Langone Health (Site #: 71177)
New York, New York, United States
RECRUITINGDuke University (Site #: 71139)
Durham, North Carolina, United States
RECRUITINGCincinnati Children's Hospital Medical Center (Site #: 71017)
Cincinnati, Ohio, United States
RECRUITINGCleveland Clinic (Site #: 71101)
Cleveland, Ohio, United States
RECRUITINGUniversity of Pennsylvania (Site #: 71111)
Philadelphia, Pennsylvania, United States
RECRUITINGVanderbilt University Medical Center (Site #: 71174)
Nashville, Tennessee, United States
RECRUITINGTime 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
Time frame: From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years
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
Time frame: From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years
Time from randomization to death
Time frame: 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
Time frame: From date of randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years
Frequency of Acute Rejection (AR)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Number of ALI events occurring from date of randomization until date of end of treatment visit, an average of 1 year.
Rate of change in lung function measures (forced expiratory volume [FEV1] and forced vital capacity [FVC])
Time frame: Rate of change occurring from date of randomization until date of end of treatment visit, an average of 1 year.
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