LAM-001 in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome.

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.

Timeline

Start

2023-08-17

Primary completion

2026-12

Completion

2026-12

Publications

• Background Gillen JR, Zhao Y, Harris DA, LaPar DJ, Kron IL, Lau CL. Short-course rapamycin treatment preserves airway epithelium and protects against bronchiolitis obliterans. Ann Thorac Surg. 2013 Aug;96(2):464-72. doi: 10.1016/j.athoracsur.2013.04.068. Epub 2013 Jun 24.
• Background Gillen JR, Zhao Y, Harris DA, Lapar DJ, Stone ML, Fernandez LG, Kron IL, Lau CL. Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a murine model. Ann Thorac Surg. 2013 May;95(5):1768-75. doi: 10.1016/j.athoracsur.2013.02.021. Epub 2013 Apr 2.
• Background Zhao Y, Gillen JR, Meher AK, Burns JA, Kron IL, Lau CL. Rapamycin prevents bronchiolitis obliterans through increasing infiltration of regulatory B cells in a murine tracheal transplantation model. J Thorac Cardiovasc Surg. 2016 Feb;151(2):487-96.e3. doi: 10.1016/j.jtcvs.2015.08.116. Epub 2015 Sep 7.
• Background Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998 Jul;31(5):335-40. doi: 10.1016/s0009-9120(98)00045-9.
• Background Bak S, Tischer S, Dragon A, Ravens S, Pape L, Koenecke C, Oelke M, Blasczyk R, Maecker-Kolhoff B, Eiz-Vesper B. Selective Effects of mTOR Inhibitor Sirolimus on Naive and CMV-Specific T Cells Extending Its Applicable Range Beyond Immunosuppression. Front Immunol. 2018 Dec 17;9:2953. doi: 10.3389/fimmu.2018.02953. eCollection 2018.
• Background Sonis S, Treister N, Chawla S, Demetri G, Haluska F. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients. Cancer. 2010 Jan 1;116(1):210-5. doi: 10.1002/cncr.24696.
• Background Boers-Doets CB, Raber-Durlacher JE, Treister NS, Epstein JB, Arends AB, Wiersma DR, Lalla RV, Logan RM, van Erp NP, Gelderblom H. Mammalian target of rapamycin inhibitor-associated stomatitis. Future Oncol. 2013 Dec;9(12):1883-92. doi: 10.2217/fon.13.141.
• Background Vigarios E, Epstein JB, Sibaud V. Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors. Support Care Cancer. 2017 May;25(5):1713-1739. doi: 10.1007/s00520-017-3629-4. Epub 2017 Feb 22.
• Background Pilotte AP, Hohos MB, Polson KM, Huftalen TM, Treister N. Managing stomatitis in patients treated with Mammalian target of rapamycin inhibitors. Clin J Oncol Nurs. 2011 Oct;15(5):E83-9. doi: 10.1188/11.CJON.E83-E89.
• Background de Oliveira MA, Martins E Martins F, Wang Q, Sonis S, Demetri G, George S, Butrynski J, Treister NS. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol. 2011 Oct;47(10):998-1003. doi: 10.1016/j.oraloncology.2011.08.009. Epub 2011 Sep 3.

Drugs

Indications