Clinical trial NCT05938920: Study Evaluating INS018_055 Administered Orally to Subjects with Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis (IPF)
Keywords: Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Lead sponsor: InSilico Medicine Hong Kong Limited
Sponsor class: INDUSTRY
First posted: 2023-07-11
Enrollment: 71
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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. 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
5. Meeting all of the following criteria during the screening period:

   1. FVC ≥40% predicted of normal
   2. DLCO corrected for Hgb ≥25% and ≤80% predicted of 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 during the screening period, 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

Other protocol inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Percentage of patients who have at least 1 treatment-emergent adverse event (TEAE)
timeFrame: Day 1 (Visit 2) up to Week 12 (End of Treatment (EOT))
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Time at which the maximum plasma concentration occurred (tmax) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: 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)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: 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)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Area under the plasma concentration-time curve from time zero to infinity (∞) (AUC0-∞) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Terminal elimination half-life (t1/2) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Terminal elimination rate constant (λz) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Apparent clearance (CL/F) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Apparent volume of distribution (Vz/F) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Accumulation ratio (Rac) for Cmax and AUC of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Trough plasma concentration (Ctrough) of INS018_055 and metabolites (INS018_063 and INS018_095)
timeFrame: Following the first dose on Day 1 (Visit 2) and the last dose during Week 12 (Visit 6, End of Treatment (EOT))
measure: Relative change in Forced Vital Capacity (FVC) in mL
timeFrame: Week 0/Visit 2 up to Week 12
measure: Percentage change in FVC in mL
timeFrame: Week 0/Visit 2 up to Week 12
measure: Absolute and relative change in FVC % predicted
timeFrame: Week 0/Visit 2 up to Week 12
measure: Change in Diffusion Capacity of the lung for Carbon Monoxide (DLCO) % predicted
timeFrame: Week 0/Visit 2 to Week 12
measure: Change in Leicester Cough Questionnaire (LCQ)
timeFrame: Week 0 to Week 4, 8 and 12
measure: Change in 6-Minute Walk Distance (6MWD) in meters
timeFrame: Week 0 to Week 12
measure: Number of acute IPF exacerbations
timeFrame: Week 0 up to Week 12
measure: Number of days hospitalized for acute IPF exacerbations
timeFrame: Week 0 to up Week 12
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Chest Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Haikou
country: China
facility: Hainan General Hoapital
state: Hainan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Shenyang
country: China
facility: The Shengjing Hospital of China medical university
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: The West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital - Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: