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

NCT06476132 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT CTOT-47
• Study Type: interventional
• Target: 234
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

Lung Transplant

Keywords

Lung Transplant; Belumosudil; CLAD; Acute Rejection; Lymphocytic Bronchiolitis; Organizing Pneumonia; Acute Lung Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Time from randomization to first occurrence of probable or definite CLAD (per ISHLT 2019 standard defined criteria) or lung retransplant

  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.

Study Arms (2)

Belumosudil plus maintenance IS

EXPERIMENTAL

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

Placebo + maintenance IS

PLACEBO COMPARATOR

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

Interventions

Belumosudil DRUG

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.

Belumosudil plus maintenance IS

Placebo for Belumosudil DRUG

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.

Placebo + maintenance IS

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Single or bilateral lung transplant recipient age ≥ 12 years
• 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.
• 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
• 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
• Cytomegalovirus (CMV) polymerase chain reaction (PCR) negative within 30 days of enrollment
• 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
• Receiving Calcineurin Inhibitor (CNI)-based maintenance Immunosuppression (IS) regimen

You may not qualify if:

• Multi-organ transplants involving more than one organ type (e.g., heart-lung)
• Prior organ transplant or prior bone marrow transplant/hematopoietic stem cell transplantation
• Greater than 120 days after a qualifying biopsy
• Clinical AMR prior to enrollment. Subclinical AMR is permitted if 90 days or greater prior to enrollment.
• Diagnosed with probable or definite CLAD according to International Society for Heart and Lung Transplantation (ISHLT) guidelines prior to enrollment.
• Posttransplant treatment with anti-thymocyte globulin within 30 days or alemtuzumab or any other prohibited medication within 90 days prior to enrollment.
• Epstein-Barr virus (EBV) seronegative recipient who received EBV positive donor lung(s).
• Treatment with any other investigational pharmacologic agent within 30 days prior to enrollment.
• Significant active uncontrolled infection which, in the opinion of the investigator, would place the participant at increased risk.
• Current use of sirolimus or everolimus.
• Recipient human immunodeficiency virus (HIV) positive.
• Recipient Hepatitis B surface antigen positive or Hepatitis B core antibody positive.
• Received lung(s) from a donor with known Hepatitis B virus (HBV) including Hepatitis B core antibody positive donors.
• 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).
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

University of California, Los Angeles (Site #: 71123)

Los Angeles, California, 90095, United States

RECRUITING

Stanford University (Site #: 71141)

Palo Alto, California, 94304, United States

NOT YET RECRUITING

Johns Hopkins (Site #: 71119)

Baltimore, Maryland, 21287, United States

RECRUITING

University of Minnesota (Site 71151)

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University (Site #: 71157)

St Louis, Missouri, 63130, United States

RECRUITING

NYU Langone Health (Site #: 71177)

New York, New York, 10016, United States

RECRUITING

Duke University (Site #: 71139)

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center (Site #: 71017)

Cincinnati, Ohio, 45229, United States

RECRUITING

Cleveland Clinic (Site #: 71101)

Cleveland, Ohio, 44195, United States

RECRUITING

University of Pennsylvania (Site #: 71111)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University Medical Center (Site #: 71174)

Nashville, Tennessee, 37232, United States

RECRUITING

University Health Network/Toronto General Hospital (Site #: 71121)

Toronto, Ontario, Canada

RECRUITING

Related Links

• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)

MeSH Terms

Conditions

Organizing Pneumonia; Acute Lung Injury

Interventions

belumosudil

Condition Hierarchy (Ancestors)

Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Lung Injury

Study Officials

• Scott M. Palmer, M.D., M.H.S.

  Duke University Medical Center: Transplantation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: June 26, 2024
• Study Start: March 12, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (11); CA (1)