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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).
Full 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.
Enrollment
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Volunteers
Inclusion criteria
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:
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:
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
Females of childbearing potential must satisfy following:
Male participants must:
Ability to adhere to the study visit schedule and understand and comply with all protocol requirements.
Ability to understand and provide written informed consent
Exclusion criteria
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
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:
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:
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
Primary purpose
Allocation
Interventional model
Masking
85 participants in 3 patient groups, including a placebo group
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Central trial contact
IRulya Therapeutics
Data sourced from clinicaltrials.gov
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