A Randomized, Placebo-controlled Phase 2 Study to Demonstrate the Safety and Efficacy of the Addition of LAM-001 to Standard Immunosuppression Therapy for Chronic Lung Allograft Dysfunction (BOS).
The goal of this clinical trial is to learn about the safety and effectiveness of LAM-001 in patients who have developed bronchiolitis obliterans syndrome (BOS), a form of chronic rejection, after lung transplantation. The main questions it aims to answer are: * Is LAM-001 safe in these patients? * Is LAM-001 effective in slowing BOS progression? Participants will: * Be randomly assigned to inhale either LAM-001 or placebo (a look-alike substance that contains no active drug) daily for 48 weeks * Attend 10 study visits (mixture of in-person and telehealth) over the 48 week period * Undergo pulmonary function testing, bronchoscopy, lab testing, and physical examination * Submit weekly home spirometry monitoring Researchers will compare participants assigned to LAM-001 versus placebo to see if LAM-001 is safely tolerated and to assess the effectiveness of LAM-001 on slowing BOS progression.
• Age \> 18 years old
• Recipient of a double pulmonary allograft at least 12 months before study entry
• Subjects with clinically diagnosed CLAD-BOS phenotype (all 3 required)
‣ BOS defined as screening FEV1 between 85-51% of the baseline as defined by the 2 highest FEV1 measures at least 3 weeks apart.
⁃ Diagnosis within 12 months of screening visit.
⁃ FEV1 decline is persistent as defined by decline sustained for \> 30 days.
• Currently receiving Standard Immunosuppression. This is defined as a combination of 3 medications including Prednisone, Mycophenolate or Azathioprine, and Tacrolimus or Cyclosporine. The dosing should be stable for 4 weeks prior to screening.
• Absence of oral sirolimus or everolimus treatment for at least 4 weeks prior to screening based on the half-life and resolution of the tissue effects
• Stable enough to enable routine post-transplant bronchoscopy with BAL and biopsy when indicated
• Capable of understanding the purposes and risks of the study
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry
• Women of childbearing potential if sexually active must agree to using highly effective contraception during study and for 90 days after discontinuation of study treatment
• Women of childbearing potential must refrain from breast feeding or donating eggs for the duration of the study and for 90 days after the last dose of study treatment
• Male participants must agree to use a condom during sexual contact with a female of childbearing potential while participating in the study and for 90 days following discontinuation of investigational product use
• Male participants must refrain from donating sperm for the duration of the study and for 90 days after the last dose of study treatment