LAM-001 for the Treatment of Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)

NCT05798923 | Recruiting Phase 2 FDA Drug

• 1 other identifier: LAM-001-PAH-CLN01
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 2, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LAM-001 in Adults with Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD).

Conditions

Pulmonary Hypertension Due to Lung Diseases and Hypoxia

Keywords

Interstitial Lung Disease

Outcome Measures

Primary Outcomes (2)

• To determine the change in PVR at 24 weeks

  Change in PVR at 24 weeks as measured with Right Heart Cath

  24 weeks

• To determine the safety and tolerability of LAM-001 (inhaled sirolimus) as an add-on therapy in adults with PH associated with interstitial lung diseases (PH-ILD)

  Change in oxygenation and Incidence of exacerbation of underlying lung disease

  24 weeks

Secondary Outcomes (4)

• To assess the effect of LAM-001 as an add-on therapy in adults with PH-ILD on exercise tolerance as assessed by the placebo-corrected change in 6MWD after 24 weeks

  24 weeks

• To assess the effect of LAM-001 on clinical worsening at 24 weeks

  24 weeks

• To assess the effect of LAM-001 as measured by change from baseline in WHO Functional Class at 24 weeks

  24 weeks

• To characterize the dose-response relationship of LAM-001

  24 weeks

Study Arms (3)

Matched Placebo

PLACEBO COMPARATOR

Placebo (1 or 2 oral inhalations) administered once daily via a Dry Powder Inhaler (DPI)

Drug: Placebo

LAM-001 - High Dose

ACTIVE COMPARATOR

LAM-001 (2, 100 mcg oral inhalations) once daily via a Dry Powder Inhaler (DPI)

Drug: LAM-001

LAM-001 - Low Dose

ACTIVE COMPARATOR

LAM-001 (1, 100 mcg oral inhalation) once daily via a Dry Powder Inhaler (DPI)

Drug: LAM-001

Interventions

LAM-001 DRUG

LAM-001 administered via dry powder inhaler

LAM-001 - High Dose; LAM-001 - Low Dose

Placebo DRUG

Matching placebo administered via dry powder inhalation

Matched Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years (\>70 y/o requires medical monitor approval)
• Diagnosis of PH-ILD as defined by CT imaging within 1 year of screening that demonstrates diffuse parenchymal lung disease or abnormal PFTs (see IC #3) associated with one of the following:
• Idiopathic interstitial pneumonia (IIP) including:
• Idiopathic pulmonary fibrosis (IPF)
• Idiopathic nonspecific interstitial pneumonia
• Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
• Unclassifiable idiopathic interstitial pneumonia
• Chronic hypersensitivity pneumonitis (CHP)
• CTD ILD patients with lung disease findings of \<65% predicted FVC in the setting of diagnosed Connective Tissue Disease
• Pulmonary function tests within 6 months prior to Screening as follows:
• Forced vital capacity (FVC \<65% predicted and a DLCO \>30) for patients with confirmatory high- resolution computed tomography (CT) indicating fibrotic lung disease
• For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population- based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility.
• Hemodynamics consistent with a diagnosis of precapillary PH (mPAP \> 25 mmHg, PCWP \< 15 mmHg, PVR \> 4.0 WU)
• Symptomatic pulmonary hypertension classified as WHO Functional Class II or III
• MWD ≥ 100 and ≤ 450 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value.

You may not qualify if:

• Clinical and/or radiologic evidence of moderate to severe emphysema
• Clinical diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), supported by imaging study (e.g. ventilation-perfusion (VQ) scan, CT pulmonary angiogram (CTPA) or pulmonary angiography with findings that establish CTEPH. In the absence of a clinical diagnosis of CTEPH, an imaging study is not required.
• Received IV inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to Week 0 Visit
• History of more than moderate obstructive sleep apnea that is untreated
• Prior exposure to oral sirolimus or any other mTOR inhibitor within the last 90 days
• Smoking, vaping or e-cigarette use within 90 days of Week 0 visit
• Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Week 0 Visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
• Uncontrolled systemic hypertension as evidenced by sitting systolic BP \> 170 mmHg or sitting diastolic BP \> 100 mmHg during Screening Visit after a period of rest
• Systolic BP \< 90 mmHg during Screening Visit or at baseline
• History of known pericardial constriction
• RHC contraindicated during the study per investigator
• Personal or family history of long QTc syndrome or sudden cardiac death
• Cerebrovascular accident within 90 days of the Week 0 Visit
• History of restrictive or constrictive cardiomyopathy
• Left ventricular ejection fraction \< 45% on echocardiogram performed within 6 months prior to Screening Period (or done as a part of the Screening Period)

Sponsors & Collaborators

• OrphAI Therapeutics: lead

Study Sites (3)

University of Arizona

Tucson, Arizona, 85748, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

NOT YET RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Hypoxia; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

OrphAI Therapeutics

CONTACT

2034332737; aclinical@orphai-therapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple dose (100 mcg or 200 mcg) or placebo on top of SOC

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 5, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): July 16, 2027
• Study Completion (Estimated): August 30, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)