Ignite Creation Date:
2025-12-24 @ 4:20 PM
Ignite Modification Date:
2026-03-13 @ 3:22 PM
Study NCT ID:
NCT06018766
Status:
RECRUITING
Last Update Posted:
2024-12-09
First Post:
2023-06-01
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
LAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.
Sponsor:
Steven Hays, MD
Organization:
Study Overview
Official Title:
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).
Status:
RECRUITING
Status Verified Date:
2024-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INSPO-BOS
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 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.
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.
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 after lung transplantation. Whereas the development of BOS is rare within the first year after lung transplantation, annual increments of approximately 10% are recorded in subsequent years, resulting in a cumulative incidence range of 40-50% within the first five years and 70-80% within 10 years of transplantation.
No current effective treatment for BOS exists. BOS represents the leading cause of morbidity and mortality after lung transplantation, limiting 5-year survival to well below other solid organ transplants. BOS is characterized by an inexorable lung function decline despite currently available immunomodulatory treatments. Sirolimus has been shown to block T-cell proliferative effects induced by cytokines, alloantigens, and mitogens in a dose-dependent manner(4, 5). Oral sirolimus has been shown in small studies to have a beneficial impact on rapidly progressive BOS; however, administration in this patient population has been challenged by a high degree of intolerance with the side effects. The development of LAM-001 for lung transplant related BOS, conceptually a T-cell driven process against transplanted alloantigen, is based on the principal hypothesis that administration of a sirolimus dose to the rejecting lung allograft(s) by inhalation will result in improved efficacy by depositing higher drug concentrations directly within the allograft by inhalation than would be achieved by oral administration due to systemic toxicities associated with oral sirolimus. Because of known reduced systemic bioavailability of LAM-001 compared to oral sirolimus dosing, amelioration of the substantial adverse event profile compared to oral drug is expected. LAM-001 is also expected to reduce serious complication risks by obviating requirements for maintenance and augmented immune drugs used to treat BOS.
The primary objective is to assess the clinical efficacy of LAM-001 in lung transplant recipients with bronchiolitis obliterans syndrome as measured by progression free survival and change in forced expiratory volume in one second (FEV1) over a 48-week period. Another primary objective is to assess the safety and tolerability of LAM-001 in lung transplant recipients with bronchiolitis obliterans syndrome.
Secondary objectives are:
* To determine the impact of LAM-001 on genetic markers of bronchiolitis obliterans syndrome and activation of the mammalian target of rapamycin (mTOR) pathway by measuring chronic lung allograft dysfunction signature gene profiling and mTOR pathway activation in bronchoalveolar lavage fluid
* To determine whether donor-derived cell-free DNA (%ddcfDNA) will predict ongoing injury (versus cessation of BOS progression) by measuring %ddcfDNA in randomized subjects. % ddcfDNA will be correlated with clinical outcome measures of FEV1 change, death, and re-transplantation for both randomized groups.
* To determine the levels of sirolimus in the blood and bronchoalveolar lavage (BAL) fluid, the BAL as a surrogate for levels in the lung.
No current effective treatment for BOS exists. BOS represents the leading cause of morbidity and mortality after lung transplantation, limiting 5-year survival to well below other solid organ transplants. BOS is characterized by an inexorable lung function decline despite currently available immunomodulatory treatments. Sirolimus has been shown to block T-cell proliferative effects induced by cytokines, alloantigens, and mitogens in a dose-dependent manner(4, 5). Oral sirolimus has been shown in small studies to have a beneficial impact on rapidly progressive BOS; however, administration in this patient population has been challenged by a high degree of intolerance with the side effects. The development of LAM-001 for lung transplant related BOS, conceptually a T-cell driven process against transplanted alloantigen, is based on the principal hypothesis that administration of a sirolimus dose to the rejecting lung allograft(s) by inhalation will result in improved efficacy by depositing higher drug concentrations directly within the allograft by inhalation than would be achieved by oral administration due to systemic toxicities associated with oral sirolimus. Because of known reduced systemic bioavailability of LAM-001 compared to oral sirolimus dosing, amelioration of the substantial adverse event profile compared to oral drug is expected. LAM-001 is also expected to reduce serious complication risks by obviating requirements for maintenance and augmented immune drugs used to treat BOS.
The primary objective is to assess the clinical efficacy of LAM-001 in lung transplant recipients with bronchiolitis obliterans syndrome as measured by progression free survival and change in forced expiratory volume in one second (FEV1) over a 48-week period. Another primary objective is to assess the safety and tolerability of LAM-001 in lung transplant recipients with bronchiolitis obliterans syndrome.
Secondary objectives are:
* To determine the impact of LAM-001 on genetic markers of bronchiolitis obliterans syndrome and activation of the mammalian target of rapamycin (mTOR) pathway by measuring chronic lung allograft dysfunction signature gene profiling and mTOR pathway activation in bronchoalveolar lavage fluid
* To determine whether donor-derived cell-free DNA (%ddcfDNA) will predict ongoing injury (versus cessation of BOS progression) by measuring %ddcfDNA in randomized subjects. % ddcfDNA will be correlated with clinical outcome measures of FEV1 change, death, and re-transplantation for both randomized groups.
* To determine the levels of sirolimus in the blood and bronchoalveolar lavage (BAL) fluid, the BAL as a surrogate for levels in the lung.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: