Inhaled LAM-001 for lung transplant patients with bronchiolitis obliterans syndrome
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).
This study is testing if an inhaled medication called LAM-001 can help lung transplant patients with bronchiolitis obliterans syndrome feel better and improve their lung function.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of California, San Francisco Academic / other |
| Drugs / interventions | Prednisone |
| Locations | 1 site (San Francisco, California) |
| Trial ID | NCT06018766 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the safety and effectiveness of LAM-001, an inhaled medication, in lung transplant recipients who have developed bronchiolitis obliterans syndrome (BOS). Participants will be randomly assigned to receive either LAM-001 or a placebo for 48 weeks, with regular monitoring through pulmonary function tests, bronchoscopy, and home spirometry. The study aims to determine if LAM-001 can slow the progression of BOS, a condition that significantly impacts lung transplant survival rates. By focusing on a targeted delivery method, the trial seeks to minimize side effects associated with traditional oral sirolimus treatments.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 who have received a double lung transplant at least 12 months prior and have a clinically diagnosed case of bronchiolitis obliterans syndrome.
Not a fit: Patients who have not been diagnosed with bronchiolitis obliterans syndrome or those who are currently on oral sirolimus or everolimus may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve lung function and survival rates for patients suffering from bronchiolitis obliterans syndrome after lung transplantation.
How similar studies have performed: While some studies have shown oral sirolimus to have beneficial effects on BOS, this inhaled approach is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
San Francisco, California
- University of California, San Francisco — San Francisco, California, United States (Recruiting)
Study contacts
- Principal investigator: Steven Hays, MD — University of California, San Francisco
- Study coordinator: Steven Hays, MD
- Email: steven.hays@ucsf.edu
- Phone: 415-336-4141
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.