Pulmonary Hypertension Due to Lung Diseases and HypoxiaPhase 2NCT05798923
LAM-001 for the Treatment of Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
A Phase 2 study testing LAM-001 in people with Pulmonary Hypertension Due to Lung Diseases and Hypoxia, run by IRulya Therapeutics Inc. at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Pulmonary Hypertension Due to Lung Diseases and Hypoxia
- What is being tested?
- LAM-001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Aug 2023to Feb 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-85 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)
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- Unclassifiable idiopathic interstitial pneumonia
- Chronic hypersensitivity pneumonitis (CHP)
- CTD ILD patients FVC ≥40% predicted and <70% predicted in the setting of diagnosed Connective Tissue Disease
- Pulmonary function tests at Screening as follows:
- Forced vital capacity (FVC ≥40% predicted and a DLCO corrected for hemoglobin >25%) for patients with confirmatory high-resolution computed tomography (CT) indicating fibrotic lung disease (greater than 10% fibrosis)
- 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 > 20 mmHg, PCWP < 15 mmHg, PVR ≥ 4.0 WU)
- Symptomatic pulmonary hypertension classified as WHO Functional Class II or III
- 6MWD ≥ 100 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value
- Stable PH disease-specific therapy with a stable regimen for 180 days prior to screening and stable dose for at least 90 days prior to screening. SOC PH medications are not required
- Stable dose is defined as no change in dose
- CTD ILD patients are not required to be on SOC ILD therapy but if they are, must be a stable dose for 90 days and stable regimen for 180 days
- Females of childbearing potential must satisfy following:
- Have 2 negative pregnancy tests as verified by the investigator prior to starting study and must agree to ongoing pregnancy testing during the study and at end of study treatment.
- If sexually active, must have used, and agree to continue to use, highly effective contraception without interruption, for at least 30 days prior to starting investigational product (IP), during the study (including dose interruptions), and for 90 days after discontinuation of study treatment.
- Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 90 days after the last dose of study treatment.
- Male participants must:
- Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made from natural (animal) membrane (for example, polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 90 days following IP discontinuation, even if he has undergone a successful vasectomy.
- Refrain from donating sperm for the duration of the study and for 90 days after the last dose of study treatment.
- Ability to adhere to the study visit schedule and understand and comply with all protocol requirements.
- Ability to understand and provide written informed consent
Who cannot join
- Clinical evidence of moderate or severe emphysema or radiologic evidence of greater than 15% emphysema and/or radiologic evidence of moderate to severe emphysema
- Pneumoconiosis or WHO group 5 fibrotic disorders such as sarcoidosis
- 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
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- 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 unless the subject has a prior history of low asymptomatic systemic blood pressure and is reviewed by the sponsor's medical monitor
- 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)
- Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months prior to Screening Visit).
- Known diagnosis (as determined by echocardiography) of significant (≥ 2+ regurgitation or stenotic) mitral valve or aortic valvular disease
- Any of the following clinical laboratory values during the Screening Period prior to Week 0 Visit:
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3x upper limit of normal (ULN) or total bilirubin > 2 x ULN within 28 days of Week 0 Visit
- Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of Week 0 Visit or required renal replacement therapy within 90 days
- History of opportunistic infection (e.g., invasive candidiasis or Pneumocystis pneumonia) within 6 months prior to Screening; serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening
- History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or lactose excipients in IP
- Major surgery within 8 weeks prior to Week 0 Visit. Participants must have completely recovered from any previous surgery prior to Week 0 Visit
- Prior heart or heart-lung transplants
- Life expectancy of < 12 months (per PI determination)
- Pregnant or breastfeeding females
- At any time in the 30 days prior to the Screening Period received > 20 mg/day of prednisone (or equivalent) or started or changed the dose of a systemic corticosteroid. Participants receiving stable doses of ≤ 20 mg prednisone (or equivalent) in 30 days prior to the Screening Period are permitted in the study.
- History of active malignancy within the past 2 years, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin or low grade malignancy that is followed clinically but for which no active therapy is planned (after discussion with the sponsor medical monitor)
- History of clinically significant (as determined by the investigator) non-PH related cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or other disease that may limit participation in the study
- Participation in another clinical trial involving intervention with another investigational drug or approved therapy for investigational use within 4 weeks prior to Week 0 Visit, or if the half-life of the previous product is known, within 5x the half-life prior to Week 0 Visit, whichever is longer
- Participation in another clinical trial involving an investigational device within 4 weeks prior to Week 0 Visit
- Any recreational drug use (cocaine, marijuana, etc.) within 90 days
- Unwillingness or inability to comply with the protocol- required procedures
- Subjects with 3 or more of the following risk factors for LV disease:
- BMI greater than 32
- Systemic Hypertension being actively treated
- Diabetes Mellitus
- Atrial Fibrillation
- Untreated Severe Obstructive Sleep Apnea
- Evidence of active or untreated latent tuberculosis
- Current Alcohol Use Disorder or testing positive in the 6 months prior to screening for Amphetamines, Methamphetamines or Cocaine
- Ongoing bacterial, viral or fungal lung infection requiring active treatment
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 3 recruiting
- Not yet recruiting
Brigham & Women's Hospital
Boston, Massachusetts, 02115
IRulya Therapeutics, clinical@irulya.com
Claire Cutting, MD
- Active, not recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
- Recruiting
Temple Lung Center, Temple University
Philadelphia, Pennsylvania, 19140
IRulya Therapeutics, clinical@irulya.com
Rohit Gupta, MD
- Recruiting
University of Arizona
Tucson, Arizona, 85748
IRulya Therapeutics, clinical@irulya.com
Franz Rischard, DO
About this study
Official title: 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)
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).
Read the detailed description
A Two-Part Phase 2 study to Assess LAM-001 (Inhaled Sirolimus) for the Treatment of Pulmonary Hypertension - Part A was a Single-Arm, Open-Label, Exploratory Study in Group 1 and Group 3 PH Patients (Completed) and Part B is 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).
In Part B, approximately 75 participants will receive standard of care plus LAM- 001 (inhaled sirolimus) 100 mcg, 200 mcg or placebo by oral inhalation once daily for the first 24 weeks of the study (Core Study).
Participants who complete the first 24 weeks on treatment and appear to have a favorable benefit-risk profile will be eligible to continue receiving LAM- 001 at their current dose level for the remainder of the study (Open-Label Extension Period) for an additional 12 months.
All participants will complete evaluations during a Follow-Up Period of 4 weeks.
Part A was a single-arm, open-label, exploratory study assessing the efficacy and safety of LAM-001 as an add-on therapy for the treatment of 10 WHO Functional Class III participants with WSPH Group 1 or Group 3 pulmonary hypertension that has been completed. Part B is ongoing.
- Being tested
- Placebo, LAM-001
- Keywords
- Interstitial Lung Disease
- Medical subject headings
- Hypoxia, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matching placebo administered via dry powder inhalation
LAM-001Drug
LAM-001 administered via dry powder inhaler
| Study group | Role | What they receive |
|---|---|---|
| Matched Placebo | Placebo comparator | Placebo (1 or 2 oral inhalations) administered once daily via a Dry Powder Inhaler (DPI) Receives: Drug: Placebo |
| LAM-001 - High Dose | Active comparator | LAM-001 (2, 100 mcg oral inhalations) once daily via a Dry Powder Inhaler (DPI) Receives: Drug: LAM-001 |
| LAM-001 - Low Dose | Active comparator | LAM-001 (1, 100 mcg oral inhalation) once daily via a Dry Powder Inhaler (DPI) Receives: Drug: LAM-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the change in PVR at 24 weeks
Change in PVR at 24 weeks as measured with Right Heart Cath
Measured: 24 weeks
Secondary outcomes (6)
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
Placebo-corrected change in 6MWD at 24 weeks
Measured: 24 weeks
To assess the effect of LAM-001 on Clinical Worsening at 24 weeks
Incidence of Clinical Worsening and time to first event through 24 Weeks. Clinical Worsening is defined as one of the following:
- Death
- Hospitalization related to worsening respiratory status/respiratory decompensation (>24 hours)
- Worsened WHO functional class AND symptomatic >15% decline in 6MWD from baseline directly related to the disease at 2 consecutive visits at least 24 hours apart
- Symptomatic >10% decline from baseline FVC confirmed with repeat testing
Measured: 24 weeks
To assess the effect of LAM-001 as measured by change from baseline in WHO Functional Class at 24 weeks
Percent of patients maintaining or improving Functional Class at 24 weeks
Measured: 24 weeks
To characterize the dose-response relationship of LAM-001 to identify the optimal therapeutic dose for Phase 3
PK analysis of LAM-001
Measured: 24 weeks
To assess the pharmacodynamic effect of LAM-001 as measured by change from baseline in NT-proBNP at 24 weeks
Change from baseline in NT-proBNP at 24 weeks
Measured: 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)
Bronchial hyperreactivity following initial dose of LAM-001
Frequency, incidence and severity of
- Adverse events (AEs)
- Local and systemic adverse events of special interest (AESI)
- Treatment emergent adverse events (TEAEs)
- Serious adverse events (SAEs)
Number of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs)
Change in oxygenation:
- At rest: change in saturation as assessed by pulse oximetry when on baseline oxygen, sufficient to maintain 85% saturation.
Physical examination, including oral soft tissue examinations
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2023
- Study start30 Aug 2023
- Primary completionMar 2028 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Hypertension Due to Lung Diseases and HypoxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multiple dose (100 mcg or 200 mcg) or placebo on top of SOC
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRulya Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05798923
- Sponsor's protocol ID
- LAM-001-PAH-CLN01
- Status last verified
- Oct 2026
- First submitted
- 13 Mar 2023
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No