Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about INS018_055 in adults with Idiopathic Pulmonary Fibrosis (IPF). The primary objective is to evaluate the safety and tolerability of INS018_055 orally administered for up to 12 weeks in adult subjects with IPF compared to placebo.

Official Title
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A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis (IPF)

Intervention / Treatment
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* Drug: INS018_055
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥40 years based on the date of the written informed consent form Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines In a stable condition and suitable for study participation based on the results of medical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluation Subjects with background pirfenidone or nintedanib may be enrolled if their regimen of antifibrotic therapy has been stable for > 8 weeks prior to Visit 1 Meeting all of the following criteria during the screening period: FVC ≥40% predicted of normal DLCO corrected for Hgb ≥25% and ≤80% predicted of normal. forced expiratory volume in the first second/FVC (FEV1/FVC) ratio >0.7 based on pre-bronchodilator value Exclusion Criteria: Acute IPF exacerbation within 4 months prior to Visit 1 and/or during the screening period, as determined by the investigator Patients who are unwilling to refrain from smoking within 3 months prior to screening and until the end of the study Female patients who are pregnant or nursing Abnormal ECG findings Other protocol inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INS018_055<br>Group 1: INS018_055 once daily up to 12 weeks, low dose Group 2: INS018_055 twice daily up to 12 weeks, low dose Group 3: INS018_055 once daily up to 12 weeks, high dose | Drug: INS018_055<br>* Pharmaceutical formulation: Capsules Mode of Administration: Oral<br>|
| Placebo Comparator: Placebo<br>Group 4: Placebo once or twice daily up to 12 weeks | Drug: Placebo<br>* Pharmaceutical formulation: Capsules Mode of Administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who have at least 1 treatment-emergent adverse event (TEAE) |  | Day 1 (Visit 2) up to Week 12 (End of Treatment (EOT)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Time at which the maximum plasma concentration occurred (tmax) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Area under the plasma concentration-time curve from time zero to dosing interval τ (AUC0-τ) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Area under the plasma concentration-time curve from time zero to time with last measurable concentration t (AUC0-t) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Area under the plasma concentration-time curve from time zero to infinity (∞) (AUC0-∞) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Terminal elimination half-life (t1/2) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Terminal elimination rate constant (λz) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Apparent clearance (CL/F) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Apparent volume of distribution (Vz/F) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Accumulation ratio (Rac) for Cmax and AUC of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Trough plasma concentration (Ctrough) of INS018_055 and metabolites (INS018_063 and INS018_095) |  | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT)) | 
| Relative change in Forced Vital Capacity (FVC) in mL |  | Week 0/Visit 2 up to Week 12 | 
| Percentage change in FVC in mL |  | Week 0/Visit 2 up to Week 12 | 
| Absolute and relative change in FVC % predicted |  | Week 0/Visit 2 up to Week 12 | 
| Change in Diffusion Capacity of the lung for Carbon Monoxide (DLCO) % predicted |  | Week 0/Visit 2 to Week 12 | 
| Change in Leicester Cough Questionnaire (LCQ) |  | Week 0 to Week 4, 8 and 12 | 
| Change in 6-Minute Walk Distance (6MWD) in meters |  | Week 0 to Week 12 | 
| Number of acute IPF exacerbations |  | Week 0 up to Week 12 | 
| Number of days hospitalized for acute IPF exacerbations |  | Week 0 to up Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis, Fibrosis, Pathologic Processes, Lung Diseases, Interstitial, Lung Diseases, Respiratory Tract Diseases