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

May 11, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients: A Randomized, Multicenter, Double Blind, Placebo-Controlled Trial (CTOT-47)

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

234

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Recruiting
        • University Health Network/Toronto General Hospital (Site #: 71121)
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles (Site #: 71123)
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University (Site #: 71141)
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins (Site #: 71119)
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota (Site 71151)
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Recruiting
        • Washington University (Site #: 71157)
        • Contact:
    • New York
      • New York, New York, United States, 10016
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University (Site #: 71139)
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center (Site #: 71017)
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic (Site #: 71101)
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center (Site #: 71174)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant and/or parent or guardian must be able to understand the purpose of the study, 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 60 to 550 days after lung transplant with evidence of allograft injury histology; a qualifying biopsy must have one or more of the following features alone or in combination: Acute Rejection (AR), Lymphocytic Bronchiolitis (LB), Organizing Pneumonia (OP), or Acute Lung Injury (ALI). The presence of any grade AR (A1 or greater) or LB (B1 or greater) qualifies for inclusion
  4. Females of reproductive potential and males with female partners of reproductive potential must agree to use effective contraception during treatment with belumosudil or placebo and for at least 3 months after the last dose. Participants must agree to refrain from donating or cryopreserving sperm, eggs (ova or ovocytes) for the purpose of reproduction during treatment with belumosudil or placebo and for at 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) or alanine transaminase (ALT) < 2x upper limit of normal (ULN), bilirubin < 1.5x ULN unless due to Gilbert's syndrome, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 within 30 days of enrollment
  7. Cytomegalovirus (CMV) polymerase chain reaction (PCR) negative within 30 days of enrollment
  8. In the absence of contraindications, must have received adult vaccinations or documented immunity as outlined in current National Institute of Allergy and Infectious 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 cell transplantation
  3. Greater than 120 days after a qualifying biopsy
  4. Clinical AMR prior to enrollment. Subclinical AMR is permitted if 90 days or greater prior to enrollment.
  5. Diagnosed with probable or definite CLAD according to International Society for Heart and Lung Transplantation (ISHLT) guidelines prior to enrollment.
  6. Posttransplant treatment with anti-thymocyte globulin within 30 days or alemtuzumab or any other prohibited medication within 90 days prior to enrollment.
  7. Epstein-Barr virus (EBV) seronegative recipient who received EBV positive donor lung(s).
  8. Treatment with any other investigational pharmacologic agent within 30 days prior to enrollment.
  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 antibody positive.
  13. Received lung(s) from a donor with known Hepatitis B virus (HBV) including Hepatitis B core antibody positive donors.
  14. Recipient history of Hepatitis C, Hepatitis C seropositive, or received lung(s) from a donor with known Hepatitis C (participants who have 3 months of documented consecutive undetected Hepatitis C virus PCR after treatment or spontaneous clearance 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 as posttransplant 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 physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose undue risk from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
  17. Pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belumosudil plus maintenance IS
Eligible lung transplant recipients who experience a qualifying biopsy 60 to 550 days posttransplant will be randomized into the study. 200 mg of Belumosudil (increased to 200 mg twice daily in participants receiving concurrent strong CYP3A inducers or PPIs) + maintenance IS will be administered daily for one year from randomization.
Drug: Belumosudil
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.
Placebo Comparator: Placebo + maintenance IS
Eligible lung transplant recipients who experience a qualifying biopsy 60 to 550 days posttransplant will be randomized into the study. Placebo plus maintenance immunosuppression (IS) will be administered for one year
Drug: Placebo for Belumosudil
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from randomization to the first occurrence of probable or definite CLAD (per ISHLT 2019 standard defined criteria), lung retransplant, or death
Time Frame: From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years

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

Outcome Measure
Measure Description
Time Frame
Time from randomization to first occurrence of probable or definite CLAD (per ISHLT 2019 standard defined criteria) or lung retransplant
Time Frame: From randomization until study completion - scheduled assessments: minimum of 1 year, maximum of 3 years
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
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
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
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
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.
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.
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.
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.
Rate of change occurring from date of randomization until date of end of treatment visit, an average of 1 year.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Scott M. Palmer, M.D., M.H.S., Duke University Medical Center: Transplantation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 12, 2025

Primary Completion (Estimated)

May 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

May 8, 2024

First Submitted That Met QC Criteria

June 20, 2024

First Posted (Actual)

June 26, 2024

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT CTOT-47

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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