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

Korábbi kezelés

• Prior organ transplant or prior bone marrow transplant/hematopoietic stem cell transplantation
• Active AMR unless resolved and no treatments with prohibited medications for > 90 days 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.
• Received lung(s) from a donor with known Hepatitis B virus (HBV) including Hepatitis B core antibody positive donors.

Más betegség

• Multi-organ transplants involving more than one organ type (e.g., heart-lung)
• Significant active uncontrolled infection which, in the opinion of the investigator, would place the participant at increased risk.
• Recipient human immunodeficiency virus (HIV) positive.
• Recipient Hepatitis B surface antigen positive or Hepatitis B core antibody positive.
• Incompletely treated Hepatitis C (absence of ongoing treatment and post-transplant negative HCV PCR)
• 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.

Laborértékek

• 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.

Egyéb

• Greater than 160 days after a qualifying biopsy
• Current use of sirolimus or everolimus.
• Pregnant or breastfeeding

• 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
• A qualifying biopsy obtained 60 to 760 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
• 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 or, if detected, <200 IU/ml in the absence of any signs of active infection, 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
• Intent to receive calcineurin inhibitor (CNI)-based maintenance Immunosuppression (IS) regimen