A Study to Investigate Leramistat in Patients With IPF

Study Overview
=================
Brief Summary
-----------------
To compare the effect of daily oral dosing of leramistat over 12 weeks with placebo in participants aged 40 years or older with idiopathic pulmonary fibrosis (IPF).

Detailed Description
-----------------
This will be a Phase 2, double-blind, placebo-controlled, 2-arm, parallel-group, multi-centre study to investigate leramistat treatment of patients aged 40 years or older with IPF. The study is planned to consist of the following parts: Screening period: 1 to 28 days (Weeks -4 to -1). Treatment period: a 12-week blinded, placebo-controlled treatment period (Weeks 1 to 12). Follow up period: 56 days (Weeks 13 to 20). All participants will return for a follow-up visit 56 days after their final dose. Randomization will be stratified by concomitant use of an approved anti-fibrotic drug (nintedanib or pirfenidone) at randomization versus no concomitant use of an approved anti-fibrotic drug at randomization. Number of Participants: Approximately 150 participants will be enrolled and randomly assigned in a 2:1 ratio to receive either leramistat or matched placebo. If the participant is receiving nintedanib or pirfenidone treatment, it should be stable for at least 8 weeks prior to study entry and be predicted to remain stable during the course of the study. The maximum duration of participation (including screening period and follow-up) is 24 weeks. Data Monitoring/Other Committee: A DSMB has been appointed for this study.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Efficacy and Safety of Leramistat in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: Leramistat
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of IPF based on: a. ATS/ERS/JRS/ALAT guidelines (Raghu, 2022) as confirmed by the investigator based on chest high-resolution computed tomography (hrCT) scan taken within 3 years of Screening and, if available, surgical lung biopsy b. UIP or probable UIP hrCT pattern consistent with the clinical diagnosis of IPF, as confirmed by central review prior to baseline (if indeterminate, hrCT findings of IPF may be confirmed locally by historical biopsy). Has an FVC ≥45% of predicted. Has a DLCO corrected for hemoglobin ≥25% and ≤80% of predicted. Minimum distance on 6MWT of 150 meters. Has a FEV1/FVC ratio >0.70. If on anti-fibrotics, only the approved treatments of nintedanib or pirfenidone are allowed. Participants must be on a stable dose for at least 8 weeks prior to Visit 1 Has a life expectancy of at least 12 months (in the opinion of the investigator). This list contains only key inclusion criteria. Exclusion Criteria: Emphysema ≥50% on hrCT or the extent of emphysema is greater than the extent of fibrosis according to the central reviewer's assessment from the most recent hrCT or if reported by the local reviewer. Any current malignancy or a history of malignancy within the previous 5 years prior to screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Abnormality in heart rate, blood pressure or 12-lead ECG at screening that in the opinion of the Investigator increases the risk of participating in the study. Significant history of drug allergy, including to leramistat or excipients, as determined by the Investigator. Allergic reaction, anaphylaxis, or other reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis or leukopenia) History of opportunistic, chronic, or recurrent infections. Participants with chronic obstructive pulmonary disease (COPD) or asthma that: require >2 maintenance therapies have experienced an exacerbation requiring hospitalization or systemic corticosteroids within 12 months prior to screening. This list contains only key exclusion criteria.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leramistat<br>Leramistat once daily | Drug: Leramistat<br>* Drug: Leramistat<br>|
| Placebo Comparator: Placebo<br>Placebo comparator | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced vital capacity (FVC) | Change from baseline in FVC versus placebo up to Week 12 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % predicted FVC | Change from baseline in %FVC up to Week 12 | 12 Weeks | 
| %DLCO | Change from baseline in %DLCO up to Week 12 | 12 Weeks | 
| Acute exacerbations | Time to first acute exacerbation up to Week 12. | 12 Weeks | 
| Forced expiratory volume | Forced expiratory volume in 1 second (FEV1) | 12 Weeks | 
| Disease progression | Decline in %FVC ≥10%, decline in %DLCO ≥15%, lung transplantation, or death. | 12 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IPF