Study Evaluating INS018_055 Administered Orally to Subjects With Idiopathic Pulmonary Fibrosis

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 Day 1, as determined by the investigator Patients who are unwilling to refrain from smoking within 6 months prior to screening and until the end of the study Female patients who are pregnant or nursing Abnormal ECG findings

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