Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Keywords
Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis, Fibrosis, Pathologic Processes, Lung Diseases, Interstitial, Lung Diseases, Respiratory Tract Diseases
Brief summary
The purpose of this revised Phase IIa study is to demonstrate safety of INS018\_055 over 12 weeks in adults with Idiopathic Pulmonary Fibrosis (IPF).
Detailed description
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by reduced quality of life (QoL) and a median survival of 3 to 4 years. While current standard of care (SoC) treatments including pirfenidone and nintedanib slow disease progression, they are not curative and poorly tolerated due to their toxicity profiles. To address the need for new treatments in IPF, InSilico Medicine is developing INS018\_055, a potent inhibitor of the serine/threonine kinase Traf2- and Nckinteracting kinase (TNIK).
Interventions
DRUGINS018_055
Pharmaceutical formulation: Tablet Mode of Administration: Oral
DRUGPlacebo
Pharmaceutical formulation: Tablet Mode of Administration: Oral
Sponsors
InSilico Medicine Hong Kong Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged ≥40 years based on the date of the written informed consent form 2. Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines 3. 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 4. Meeting all of the following criteria during the screening period: 1. FVC ≥40% predicted normal 2. DLCO corrected for Hgb ≥25% and \<80% predicted normal 3. Forced Expiratory Volume in the first second/FVC (FEV1/FVC) ratio \>0.7 based on pre-bronchodilator value
Exclusion criteria
1. Acute IPF exacerbation within 4 months prior to Visit 1 and/or Day 1, as determined by the investigator 2. Patients who are unwilling to refrain from smoking within 3 months prior to screening and until the end of the study 3. Female patients who are pregnant or nursing 4. Abnormal ECG findings
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of subjects who have at least 1 treatment-emergent adverse event (TEAE) | Day 1 (Visit 2) up to Week 12 (End of Treatment (EOT)) |
Secondary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Area under the plasma concentration-time curve from time zero to dosing interval τ (AUC0-τ) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, 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 its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Area under the plasma concentration-time curve from time zero to infinity (∞) (AUC0-∞) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Terminal elimination half-life (t1/2) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Terminal elimination rate constant (λz) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Apparent clearance (CL/F) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Apparent volume of distribution (Vz/F) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Accumulation ratio (Rac) for Cmax and AUC of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
| Time to reach maximum plasma concentration (Tmax) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, 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 |
| Trough plasma concentration (Ctrough) of INS018_055 and its major metabolites (INS018_063 and INS018_095) | Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 8, End of Treatment (EOT)) |
Countries
United States
Contacts
Primary ContactMonique Duncan
Backup ContactCarol Salter, MD, PhD
Outcome results
None listed