Status:
RECRUITING
LAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.
Lead Sponsor:
Steven Hays, MD
Collaborating Sponsors:
OrphAI Therapeutics
Conditions:
Bronchiolitis Obliterans Syndrome
Chronic Lung Allograft Dysfunction
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief 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 lun...
Detailed Description
Chronic rejection, commonly denoted as bronchiolitis obliterans (BO), obliterative bronchiolitis (OB), or bronchiolitis obliterans syndrome (BOS), is the leading cause of death beyond the first year a...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
August 17 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2026
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT06018766
Start Date
August 17 2023
End Date
October 1 2026
Last Update
December 9 2024
Active Locations (1)
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1
University of California, San Francisco
San Francisco, California, United States, 94143