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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Jun 20, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a medication called Belumosudil to see if it can help prevent a condition known as Chronic Lung Allograft Dysfunction (CLAD) in people who have received a lung transplant. CLAD can occur when the body begins to reject the transplanted lung, which can be detected through a lung biopsy showing signs of inflammation or injury. Participants in this study will take Belumosudil for 52 weeks along with their regular medications to see if it helps improve their lung health and prevent further complications.

To be eligible for the trial, participants must be at least 12 years old and have had a lung transplant. They should have a recent biopsy showing signs of rejection or inflammation. Participants will need to agree to use birth control during the study and for a short time afterward. Throughout the trial, they will be monitored closely, and their health will be assessed regularly. This study is important because it aims to find new ways to protect lung transplant patients from serious issues related to their transplants, potentially improving their long-term health and quality of life.

Gender

ALL

Eligibility criteria

• 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 90 to 410 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 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 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