LAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSteven Hays, MD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
LAM-001
DrugLAM-001 administered via dry powder inhaler
Placebo
DrugPlacebo administered via dry powder inhaler
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: LAM-001Experimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
% change in FEV1 from baseline
Patient's % change in FEV1 from baseline at 48 weeks or termination of treatment, whichever is earlier
Time frame
48 weekSecondary outcomes
1
Absolute change in FEV1
Change in FEV1 from baseline
Time frame
48 weeks2
Change in the rate of progression in FEV1
Change in rate of progression in FEV1 in the time period (up to 12 months) prior to enrollment in the clinical trial compared to rate of progression from enrollment to 48 weeks (or termination of treatment, whichever occurs first) as measured by change in FEV1/month (measured in L and as % of baseline).
Time frame
48 weeks3
Time to Progression Free Survival (PFS), Level 1
Time to Progression Free Survival (PFS) Level 1, defined as the earliest of the following: 1. Absolute decrease in the FEV1 from baseline of \>10% 2. Death from respiratory failure or re-transplantation
Time frame
48 weeksOther outcomes
1
Change in Quality of Life
Change in Quality of Life as measured by St. George's Respiratory Questionnaire -COPD (SGRQ-C). The range of scores is 0-100, with the higher scores representing more limitation in quality of life.
Time frame
48 weeks2
Change in six-minute walk distance (6MWD)
Change in 6MWD from baseline
Time frame
48 weeks3
CLAD signature gene profiling
Utilizing the endobronchial brush, we will quantify a metagene, or normalized sum of gene expression, from our previously published airway inflammation gene set, as described in our publication (PMID: 32885581). The metagene expression will be compared between randomized groups.
Time frame
3 months post randomization4
mTOR pathway activation
Utilizing the bronchioalveolar lavage fluid, we will quantify pS6S235/235 in lymphocytes using flow cytometry, to quantify mTORC1 activity, as previously published (PMID: 36066491). We will compare pS6S235/235 between randomized groups.
Time frame
3 months post randomizationSponsors and contacts
Click on the lead sponsor to view all of their trials.
Steven Hays, MD
Lead sponsor
University of California, San Francisco
Sponsor institution
OrphAI Therapeutics
Collaborator
Source ClinicalTrials.gov