Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients

Inclusion Criteria:

1. Participant and/or parent or guardian must be able to understand the purpose of thestudy, willing to participate, sign the informed consent, and if applicable assent.

2. Single or bilateral lung transplant recipient age ≥ 12 years

3. A qualifying biopsy obtained 90 to 410 days after lung transplant with evidence ofallograft injury histology; a qualifying biopsy must have one or more of thefollowing features alone or in combination: Acute Rejection (AR), LymphocyticBronchiolitis (LB), Organizing Pneumonia (OP), or Acute Lung Injury (ALI). Thepresence of any grade AR (A1 or greater) or LB (B1 or greater) qualifies forinclusion

4. Females of reproductive potential and males with female partners of reproductivepotential must agree to use effective contraception during treatment withbelumosudil or placebo and for at least 3 months after the last dose. Participantsmust agree to refrain from donating or cryopreserving sperm, eggs (ova or ovocytes)for the purpose of reproduction during treatment with belumosudil or placebo and forat least 3 months after the last dose.

5. Meeting hematologic laboratory criteria: absolute neutrophil count (ANC) >= 0.5 x 10(9)/L and platelet count >= 50 x 10(9)/L within 30 days of enrollment

6. Meeting all blood chemistry laboratory criteria: aspartate aminotransferase (AST) oralanine transaminase (ALT) < 2x upper limit of normal (ULN), bilirubin < 1.5x ULNunless due to Gilbert's syndrome, estimated glomerular filtration rate (eGFR) ≥ 30mL/min/1.73m2 within 30 days of enrollment

7. Cytomegalovirus (CMV) polymerase chain reaction (PCR) negative within 30 days ofenrollment

8. In the absence of contraindications, must have received adult vaccinations ordocumented immunity as outlined in current National Institute of Allergy andInfectious Diseases (NIAID) Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials

9. Receiving Calcineurin Inhibitor (CNI)-based maintenance Immunosuppression (IS)regimen

Exclusion Criteria:

1. Multi-organ transplants involving more than one organ type (e.g., heart-lung)

2. Prior organ transplant or prior bone marrow transplant/hematopoietic stem celltransplantation

3. Greater than 60 days after a qualifying biopsy

4. Clinical AMR (possible, probable, or definite) any time prior to or at enrollment.

5. Diagnosed with probable or definite CLAD according to International Society forHeart and Lung Transplantation (ISHLT) guidelines prior to enrollment.

6. Posttransplant treatment with anti-thymocyte globulin within 30 days or alemtuzumabor any other prohibited medication within 90 days prior to enrollment.

7. Epstein-Barr virus (EBV) seronegative recipient who received EBV positive donorlung(s).

8. Treatment with any other investigational pharmacologic agent within 30 days prior toenrollment.

9. Significant active uncontrolled infection which, in the opinion of the investigator,would place the participant at increased risk.

10. Current use of sirolimus or everolimus.

11. Recipient human immunodeficiency virus (HIV) positive.

12. Recipient Hepatitis B surface antigen positive or Hepatitis B core antibodypositive.

13. Received lung(s) from a donor with known Hepatitis B virus (HBV) including HepatitisB core antibody positive donors.

14. Recipient history of Hepatitis C, Hepatitis C seropositive, or received lung(s) froma donor with known Hepatitis C (participants who have 3 months of documentedconsecutive undetected Hepatitis C virus PCR after treatment or spontaneousclearance will not be excluded).

15. History of clinically significant surgical factors (such as phrenic nerve damage,transplant lung resection, chest wall surgery), or mechanical factors (such asposttransplant airways disease including bronchial dehiscence, stenosis, dilation,or stent placement, pleural disease) that impedes lung function.

16. Past or current medical problems, psychosocial concerns, or findings from physicalexamination or laboratory testing that are not listed above, which, in the opinionof the investigator, may pose undue risk from participation in the study, mayinterfere with the participant's ability to comply with study requirements, or thatmay impact the quality or interpretation of the data obtained from the study.

17. Pregnant or breastfeeding