LAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Steven Hays, MD
• Collaborator: OrphAI Therapeutics

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.

• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

• Patients with re-transplantation or currently listed for re-transplantation

• Patients with confirmed other causes for loss of lung function, such as acute infection, acute rejection, restrictive allograft syndrome (CLAD - RAS phenotype, see Protocol Specific Definition), etc.

• Patients with acute antibody-mediated rejection at Screening. In this context, clinically stable patients (as judged by the Investigator) with detectable donor-specific antibodies (DSA) levels at the Screening Visit are eligible for the study

• Active acute bacterial, viral, or fungal infection that has not successfully resolved in at least 4 weeks prior to the Screening Visit. Patients with chronic infection or colonization who are clinically stable as per judgement of the investigator are eligible.

• Mechanical ventilation within 12 weeks prior to the randomization

• Patient has baseline resting oxygen saturation of < 89% on room air or use of supplemental oxygen at rest at screening

• Evidence of functional airway stenosis (i.e., bronchomalacia/ tracheomalacia, airway stents, or airways requiring balloon dilatations to maintain patency) with onset after the initial diagnosis of BOS and ongoing at Screening and/or Baseline Visit

• Known hypersensitivity to sirolimus or everolimus

• Currently enrolled in another investigational trial for obstructive chronic lung allograft dysfunction (BOS)

• Patients with chronic renal failure, defined as serum creatinine > 2.5 mg/dL at screening, or requiring chronic dialysis

• Patients with liver disease and serum bilirubin > 3-fold upper limit of normal range or transaminases > 2.5 upper limit of normal range

• Patients with active malignancy within the previous 2 years, including post-transplant lymphoproliferative disorder, except for treated, localized basal and squamous cell carcinomas

• Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 6 months. This does not include minor surgical procedures for localized skin cancer.

• History of severe allergic reaction to lactose (patients with lactose intolerance are eligible)

• Patients with uncontrolled hypertension