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

NCT ID: NCT06476132

Last Updated: 2026-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

234 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-12

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Lung Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Belumosudil

Intervention Type 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.

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

Group Type PLACEBO_COMPARATOR

Placebo for Belumosudil

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott M. Palmer, M.D., M.H.S.

Role: STUDY_CHAIR

Duke University Medical Center: Transplantation

Locations

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

Los Angeles, California, United States

Site Status RECRUITING

Johns Hopkins (Site #: 71119)

Baltimore, Maryland, United States

Site Status RECRUITING

University of Minnesota (Site 71151)

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University (Site #: 71157)

St Louis, Missouri, United States

Site Status RECRUITING

NYU Langone Health (Site #: 71177)

New York, New York, United States

Site Status RECRUITING

Duke University (Site #: 71139)

Durham, North Carolina, United States

Site Status RECRUITING

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

Cincinnati, Ohio, United States

Site Status RECRUITING

Cleveland Clinic (Site #: 71101)

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania (Site #: 71111)

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt University Medical Center (Site #: 71174)

Nashville, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Paul Lopez

Role: primary

310-794-1999

Matthew Kelley

Role: primary

410-960-6547

Dean Krueger

Role: primary

612-301-4015

Brigitte Mittler

Role: primary

314-747-1931

Cecilia Deterville

Role: primary

212-263-3620

Katelyn Arroyo

Role: primary

919-684-6140

Maryam Mysorewala

Role: primary

513-636-4578

Rijuta Singh

Role: primary

216-444-3194

Maddy Fair

Role: primary

215-573-4701

Briana Swanner

Role: primary

615-327-7232

Related Links

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https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

Other Identifiers

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DAIT CTOT-47

Identifier Type: -

Identifier Source: org_study_id

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