LAM-001 for Bronchiolitis Obliterans Syndrome

(INSPO-BOS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Steven Hays, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Steven Hays, MD

Must be taking: Standard immunosuppression

Must not be taking: Sirolimus, Everolimus

Disqualifiers: Pregnancy, Re-transplantation, Acute infection, others

Prior Safety Data

Trial Summary

What is the purpose of 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.

Do I need to stop my current medications to join the trial?

The trial requires participants to continue their current standard immunosuppression medications, which include Prednisone, Mycophenolate or Azathioprine, and Tacrolimus or Cyclosporine. However, you must not be taking oral sirolimus or everolimus for at least 4 weeks before joining the study.

What data supports the effectiveness of the drug LAM-001 for Bronchiolitis Obliterans Syndrome?

Research shows that sirolimus, a component of LAM-001, can stabilize lung function in patients with bronchiolitis obliterans syndrome, and rapamycin, another component, helps reduce immune system activity that can lead to this condition.

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What safety information is available for the treatment LAM-001 (Sirolimus/Rapamycin) in humans?

Sirolimus, also known as Rapamycin, is used as an immunosuppressant but can have side effects on the lungs, such as causing lung inflammation and bleeding. In some cases, stopping the drug and using steroids helped improve lung function.

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How is the drug LAM-001 (Sirolimus) unique for treating Bronchiolitis Obliterans Syndrome?

LAM-001, which includes Sirolimus, is unique because it acts as an immunosuppressant that helps prevent the immune system from attacking the lungs, potentially stabilizing lung function in patients with Bronchiolitis Obliterans Syndrome. Unlike traditional treatments that only temporarily stabilize lung function, Sirolimus has anti-proliferative properties that may offer longer-term benefits.

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Eligibility Criteria

This trial is for adults over 18 who've had a double lung transplant at least a year ago and are now facing chronic rejection called bronchiolitis obliterans syndrome (BOS). They should have specific lung function levels, be on standard immunosuppression, and not be taking certain drugs. Participants must use effective birth control if they can have children and cannot donate sperm or eggs during the study.

Inclusion Criteria

Your lung function has been steadily decreasing for more than 30 days.

Written informed consent 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 refrain from breast feeding or donating eggs for the duration of the study and for 90 days after the last dose of study treatment

Exclusion Criteria

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

You have had an organ transplant before, or you are waiting for another organ transplant.

You are currently experiencing acute antibody-mediated rejection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to inhale either LAM-001 or placebo daily for 48 weeks. They will attend 10 study visits (mixture of in-person and telehealth) and undergo pulmonary function testing, bronchoscopy, lab testing, and physical examination. Weekly home spirometry monitoring is also required.

48 weeks

10 visits (mixture of in-person and telehealth)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression free survival and change in FEV1.

4 weeks

Participant Groups

The trial tests LAM-001's safety and effectiveness against BOS in lung transplant recipients. Patients will either inhale LAM-001 or a placebo daily for 48 weeks while undergoing regular health checks including lung function tests, with some visits possibly via telehealth.

Group I: LAM-001 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Lactose capsule to be inhaled daily for 48 weeks via Plastiape RS01 dry powder inhaler Model 7.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California, San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

Steven Hays, MD Lead Sponsor

AI Therapeutics, Inc. Industry Sponsor

OrphAI Therapeutics Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection. [2019] Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS.

2. United States pubmed.ncbi.nlm.nih.gov

Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis. [2021] To study obliterative bronchiolitis (OB), we have developed a porcine heterotopic bronchial model. Allografts obliterate within 3 weeks, the immunosuppression cyclosporine (CsA)-azathioprine (AZA)-methylprednisolone (MP) delays OB, but OB is prevented when AZA is switched to 40-0-(2-hydroxyethyl)-rapamycin (RAD). To characterize our model, we studied immune cells under various immunosuppressive conditions.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of prophylactic use of sirolimus on bronchiolitis obliterans syndrome development in lung transplant recipients. [2021] Sirolimus (SIR) has been shown to stabilize the lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, there is no long-term data on the prophylactic use of SIR in lung transplant recipients. This retrospective study examines the effects of SIR in the prevention of BOS.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Rapamycin Combined with Immature Dendritic Cells Attenuates Obliterative Bronchiolitis in Trachea Allograft Rats by Regulating the Balance of Regulatory and Effector T Cells. [2015] Obliterative bronchiolitis (OB) ranks as the major obstacle for long-term survival of lung transplantation patients. Rapamycin (Rapa) has recently been confirmed as an immunosuppressant for antirejection due to its suppressive role in T cell activation. Here, we explore the effect of Rapa combined with immature dendritic cells (imDCs) on OB in trachea allograft rats.

5. United States pubmed.ncbi.nlm.nih.gov

A retrospective 12-month study of conversion to everolimus in lung transplant recipients. [2015] Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation.

6. United States pubmed.ncbi.nlm.nih.gov

Rapamycin in lung transplantation. [2013] Rapamycin (RAPA) is a powerful immunosuppressant that also acts as an antiproliferative, which, therefore, could be useful in the treatment and prevention of bronchiolitis obliterans (BOS) in lung transplant recipients. We sought to report our experiences with RAPA in lung transplant patients with BOS that has not responded to the administration of other drugs.

7. United States pubmed.ncbi.nlm.nih.gov

Sirolimus-Induced Diffuse Alveolar Hemorrhage: A Case Report. [2017] Sirolimus is a mammalian target of the rapamycin, a protein kinase, which is responsible for inhibition of T cell and B cell proliferation. Sirolimus has side effects on lugs, and may cause cryptogenic organizing pneumonia, diffuse alveolar hemorrhage, lymphocytic pneumonitis, hypersensitivity pneumonitis, desquamative interstitial pneumonia, and pulmonary alveolar proteinosis. Diagnosis is based on the combination of clinical, radiological, histological, and pathological investigation. We report a case of diffuse alveolar hemorrhage in a 33-year-old, female renal transplant recipient. After discontinuation of sirolimus, radiological images and clinical condition of the patient got better. We also planned steroid therapy for 6 months by tapering the dosage slowly. After steroid therapy, full recovery of pulmonary functions achieved, and the patient is observed in our outpatient clinic with lack of any pulmonary symptoms.

8. Netherlands pubmed.ncbi.nlm.nih.gov

Short-course rapamycin treatment preserves airway epithelium and protects against bronchiolitis obliterans. [2021] Damage to airway epithelium is closely related to the development of bronchiolitis obliterans (BO) in pulmonary transplantation. Rapamycin protects against BO development in a murine model, but its use in patients undergoing lung transplantation is limited by its side effects. We hypothesized that short-course rapamycin dosing could be used to prevent airway epithelium loss and protect against BO development in a murine model.

9. United States pubmed.ncbi.nlm.nih.gov

Successful use in lung transplantation of an immunosuppressive regimen aimed at reducing target blood levels of sirolimus and tacrolimus. [2013] The primary aim of this study was to assess the safety and efficacy in lung transplantation of an immunosuppressive regimen aimed at achieving sirolimus and tacrolimus concentrations of 6 to 10 microg/ml and 5 to 7 ng/ml, respectively.

10. England pubmed.ncbi.nlm.nih.gov

Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis? [2022] Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.