Inclusion Criteria: 

• Participant must be at least 18 years of age, at the time of signing the informed consent.
• Participant ≥ 1 year post bilateral lung transplantation at the time of screening.
• Participants diagnosed with CLAD within 9 months prior to screening, defined as a documented ≥ 20% decline in FEV1 from PTBL (determined by the mean of the 2 highest FEV1 measurements obtained at least 3 weeks apart post-transplant). The decline must be sustained for ≥3 months. The date of CLAD diagnosis, defined as the date of the first FEV1 measurement used for diagnosis, must be within 9 months prior to screening.
• Participants presenting with CLAD Stage 1 or 2: FEV1 from > 50% to 80% of PTBL at screening and at randomization.
• Participants presenting with progressive CLAD: average decline in FEV1 of at least 1.7% per month since diagnosis at screening (eg, FEV1 decline at screening ≥10% compared with diagnosis if diagnosis is 6 months before screening, or ≥15% if diagnosis is 9 months before screening).
• Participants willing to continue all standard-of-care treatment per center protocols (prednisone [ < 30 mg with stable dose for 4 weeks] and any combination of CNI and/or CCI).
• Participants who have received at least 8 weeks of azithromycin (≥ 250 mg/day, at least 3 times a week) following the diagnosis of CLAD and prior to randomization.
• Body mass index ≥18 kg/m^2.
• Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding
• All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:
  • Male participants
    • Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 3 months after the last administration of study intervention:
      • Refrain from donating or cryopreserving sperm; PLUS, either:
        • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR
        • Must agree to use contraception as detailed below A male condom and an additional highly effective contraceptive method as described in Appendix 4 (Section 10.4: Contraceptive and barrier guidance) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
  • Female participants
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
      • Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 4 (Section 10.4: Contraceptive and barrier guidance); OR
      • Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 4 (Section 10.4: Contraceptive and barrier guidance) during the study intervention period (to be effective before starting the intervention) and for at least 3 months after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
    • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at screening and a negative urine pregnancy test before the first administration of study intervention (see Section 8.3.5). If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Informed Consent
  • Participants or their legally authorized representative must be capable of giving signed informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Privacy and Data Protection requirements including those of the Global Data Protection Regulation (GDPR) and of the French law, where applicable, and the IRB/IEC or study center.

Exclusion Criteria:

• FEV1 ≤ 50% of the post-transplant baseline value (CLAD 3 and 4).
• Participant who are enrolled in other clinical trials.
• Participants who are intolerant to belumosudil or any of its components.
• Any condition that can affect the ability to perform pulmonary function testing.
• Lung function decline that can be explained by non-CLAD causes including but not limited to acute lung allograft rejection (>A1), antibody-mediated rejection within 4 weeks of screening, airway stenosis, or tracheobronchomalacia.
• Diagnosed or treated for malignancy within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy.
• Untreated symptomatic gastroesophageal reflux disease (GERD).
• Baseline resting oxygen saturation of <88% on room air or use of supplemental oxygen at rest.
• Known prolongation of the QT interval (>480 msec), a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure.
• Ongoing proarrhythmic conditions such as uncorrected hypokalemia or clinically significant hypomagnesemia or bradycardia.
• Participants who have received therapy for CLAD other than azithromycin and standard-of-care immunosuppressants. Participants who have received alemtuzumab, pirfenidone, nintedanib, thymoglobulin, basiliximab, JAK inhibitors, high dose steroid, total lymphoid irradiation (TLI) and ECP are excluded from the study. Previous use of montelukast, fluticasone, or mTORi is allowed if discontinued at least 28 days prior to randomization. Previous induction therapy at the time of transplant (e.g., thymoglobulin, alemtuzumab, or basiliximab) is allowed. High dose steroid as induction at the time of transplant and for the treatment of acute rejection if discontinued at least 8 weeks prior to screening are allowed.
• Participants receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. For other medications known to prolong the QT interval (other than azithromycin), the risk/benefit ratio will be assessed by site Investigator.
• Received any investigational drugs since the date of lung transplantation, or any investigational device or procedure, or prohibited therapy for this study.
• Participant has had previous exposure to belumosudil.
• Platelets < 50 x 10^9 /L. Platelet transfusion is not allowed within 3 days before the screening hematological test.
• Absolute neutrophil count (ANC) > <1.5 x 10^9 /L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening and at baseline.
• Estimated Glomerular Filtration Rate (eGFR) >< 30 mL/min/1.73 m^2 using the MDRD-4 variable formula (if aged ≥ 18 years).
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN).
• Total bilirubin >1.5 × ULN (> 3 × ULN if Gilbert syndrome).
• History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease, or myasthenia gravis).
• Known history of human immunodeficiency virus (HIV).
• Active viral disease including hepatitis B virus (HBV), hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Participants must have negative viral load results confirming no evidence of active viral disease within 28 days prior to randomization.
• Active uncontrolled cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present according to Investigator’s judgement and the respective viral loads are undetectable.
• Participant is unable to swallow tablets.
• Participant is considered unlikely to adhere to treatment and/or follow the protocol in the opinion of the Investigator.
• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6).
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Participants with known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide drug are excluded from the study.
• Any country-related specific regulation that would prevent the participant from entering the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/21/23. Questions regarding updates should be directed to the study team contact.