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

NCT06018766 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LAM-001-BOS-CLN01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchiolitis Obliterans Syndrome; Chronic Lung Allograft Dysfunction; Lung Transplantation

Keywords

Bronchiolitis Obliterans Syndrome; Chronic Lung Allograft Dysfunction; Lung Transplant Rejection; Sirolimus; mTOR inhibitor; CLAD

Outcome Measures

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

  48 week

Secondary Outcomes (3)

• Absolute change in FEV1

  48 weeks

• Change in the rate of progression in FEV1

  48 weeks

• Time to Progression Free Survival (PFS), Level 1

  48 weeks

Other Outcomes (10)

• Change in Quality of Life

  48 weeks

• Change in six-minute walk distance (6MWD)

  48 weeks

• CLAD signature gene profiling

  3 months post randomization

Study Arms (2)

LAM-001

EXPERIMENTAL

Drug: LAM-001

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

LAM-001 DRUG

LAM-001 administered via dry powder inhaler

LAM-001

Placebo DRUG

Placebo administered via dry powder inhaler

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Steven Hays, MD: lead
• OrphAI Therapeutics: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 23806229 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.

  PMID: 23561805 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.

  PMID: 26481278 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.

  PMID: 9721431 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.

  PMID: 30619313 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.

  PMID: 19862817 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.

  PMID: 24295418 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.

  PMID: 28224235 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.

  PMID: 21951751 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.

  PMID: 21890398 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Steven Hays, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven Hays, MD

CONTACT

415-336-4141; steven.hays@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: August 31, 2023
• Study Start: August 17, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)