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 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.
Interventions
DRUGINS018_055
Pharmaceutical formulation: Capsules Mode of Administration: Oral
DRUGPlacebo
Pharmaceutical formulation: Capsules 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | From first dose of study drug until end of study (EOS) visit i.e. up to 13 weeks (+10 days) | TEAEs were either events with start date on or after the start of the Treatment Period and up to 17 days after EOT (end of treatment), or events with start date prior to the start of the Treatment Period whose severity worsened on or after the start of the Treatment Period and up to 17 days after EOT. CTCAE=Common Terminology Criteria for Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in Forced Vital Capacity (FVC) | Week 0/Visit 2 up to Week 12 | Decline (change) in FVC is presented from Week 0 to Week 12. FVC was assessed using standardized spirometry equipment. |
| Absolute Change From Baseline in FVC in L | Week 0/Visit 2 up to Week 12 | Decline (change) in FVC is presented from Week 0 to Week 12. FVC was assessed using standardized spirometry equipment. |
| Absolute Change in FVC % Predicted | Week 0/Visit 2 up to Week 12 | Absolute change in FVC % predicted from Week 0 to Week 12 is presented. FVC was assessed using standardized spirometry equipment |
| Relative Change in FVC % Predicted | Week 0/Visit 2 up to Week 12 | Relative change in FVC % predicted from Week 0 to Week 12 is presented. FVC was assessed using standardized spirometry equipment |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| INS018_055 30 mg QD Group 1: INS018\_055 once daily up to 12 weeks, low dose INS018\_055: Pharmaceutical formulation: Capsules Mode of administration: Oral | 18 |
| INS018_055 30 mg BID Group 2: INS018\_055 twice daily up to 12 weeks, low dose INS018\_055: Pharmaceutical formulation: Capsules Mode of administration: Oral | 18 |
| INS018_055 60 mg QD Group 3: INS018\_055 once daily up to 12 weeks, high dose INS018\_055: Pharmaceutical formulation: Capsules Mode of administration: Oral | 18 |
| Placebo Group 4: Placebo once or twice daily up to 12 weeks INS018\_055: Pharmaceutical formulation: Capsules Mode of administration: Oral | 17 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 2 | 1 |
| Overall Study | Death | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Participant Asked to Withdraw from the Trial | 1 | 0 | 0 | 0 |
| Overall Study | Participant Refused to Come In | 0 | 0 | 1 | 0 |
| Overall Study | Participant Withdrew from Treatment and Refused to do Visit 7 Follow Up Visit | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | INS018_055 30 mg QD | Total | Placebo | INS018_055 60 mg QD | INS018_055 30 mg BID |
|---|---|---|---|---|---|
| 6-minute walk distance (6-MWD) test (in meters) at Baseline | 420.81 meters (m) STANDARD_DEVIATION 122.02 | 394.85 meters (m) STANDARD_DEVIATION 89.806 | 393.21 meters (m) STANDARD_DEVIATION 73.022 | 378.04 meters (m) STANDARD_DEVIATION 76.252 | 387.26 meters (m) STANDARD_DEVIATION 80.066 |
| Age, Continuous | 65.8 years STANDARD_DEVIATION 6.99 | 66.7 years STANDARD_DEVIATION 6.73 | 68.3 years STANDARD_DEVIATION 5.28 | 65.7 years STANDARD_DEVIATION 6.82 | 67.2 years STANDARD_DEVIATION 7.77 |
| Age, Customized > 65 to ≤ 75 years | 7 Participants | 39 Participants | 13 Participants | 10 Participants | 9 Participants |
| Age, Customized ≤ 65 years | 9 Participants | 27 Participants | 4 Participants | 7 Participants | 7 Participants |
| Age, Customized >75 years | 2 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants |
| Body Mass Index at Baseline | 25.66 kg/m2 STANDARD_DEVIATION 2.08 | 25.36 kg/m2 STANDARD_DEVIATION 3.429 | 24.96 kg/m2 STANDARD_DEVIATION 3.733 | 26.41 kg/m2 STANDARD_DEVIATION 4.128 | 24.41 kg/m2 STANDARD_DEVIATION 3.399 |
| Diffusion capacity of the lung for carbon monoxide (DLCO) (actual) at Baseline | 3.7832 mmol/min/kPa STANDARD_DEVIATION 1.03476 | 3.6447 mmol/min/kPa STANDARD_DEVIATION 1.06898 | 3.6085 mmol/min/kPa STANDARD_DEVIATION 1.08683 | 3.7561 mmol/min/kPa STANDARD_DEVIATION 1.2532 | 3.4291 mmol/min/kPa STANDARD_DEVIATION 0.93188 |
| Diffusion capacity of the lung for carbon monoxide (DLCO) (% predicted) at Baseline | 47.6952 percentage STANDARD_DEVIATION 12.4107 | 47.7279 percentage STANDARD_DEVIATION 13.78235 | 49.1347 percentage STANDARD_DEVIATION 15.72199 | 48.9831 percentage STANDARD_DEVIATION 16.53697 | 45.1767 percentage STANDARD_DEVIATION 10.55849 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 71 Participants | 17 Participants | 18 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced vital capacity (FVC) at Baseline | 2.6961 liters (L) STANDARD_DEVIATION 0.44422 | 2.5848 liters (L) STANDARD_DEVIATION 0.6004 | 2.2456 liters (L) STANDARD_DEVIATION 0.47359 | 2.7616 liters (L) STANDARD_DEVIATION 0.68415 | 2.6170 liters (L) STANDARD_DEVIATION 0.6674 |
| Height at Baseline | 167.77 centimeters (cm) STANDARD_DEVIATION 5.549 | 166.11 centimeters (cm) STANDARD_DEVIATION 6.944 | 164.50 centimeters (cm) STANDARD_DEVIATION 7.874 | 166.29 centimeters (cm) STANDARD_DEVIATION 6.47 | 165.78 centimeters (cm) STANDARD_DEVIATION 7.869 |
| Leicester Cough Questionnaire (LCQ) total score at Baseline | 17.1290 scores on a scale STANDARD_DEVIATION 3.0886 | 16.3682 scores on a scale STANDARD_DEVIATION 3.32222 | 16.4370 scores on a scale STANDARD_DEVIATION 3.05011 | 15.7431 scores on a scale STANDARD_DEVIATION 3.70099 | 16.1677 scores on a scale STANDARD_DEVIATION 3.51858 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 71 Participants | 17 Participants | 18 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 7 Participants | 2 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 18 Participants | 64 Participants | 15 Participants | 16 Participants | 15 Participants |
| Weight at Baseline | 72.27 kilograms (kg) STANDARD_DEVIATION 7.395 | 70.20 kilograms (kg) STANDARD_DEVIATION 11.593 | 67.69 kilograms (kg) STANDARD_DEVIATION 12.117 | 73.32 kilograms (kg) STANDARD_DEVIATION 13.547 | 67.36 kilograms (kg) STANDARD_DEVIATION 12.141 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 18 | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 13 / 18 | 15 / 18 | 15 / 18 | 12 / 17 |
| serious Total, serious adverse events | 2 / 18 | 4 / 18 | 7 / 18 | 3 / 17 |
Outcome results
Primary
Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE)
TEAEs were either events with start date on or after the start of the Treatment Period and up to 17 days after EOT (end of treatment), or events with start date prior to the start of the Treatment Period whose severity worsened on or after the start of the Treatment Period and up to 17 days after EOT. CTCAE=Common Terminology Criteria for Adverse Events
Time frame: From first dose of study drug until end of study (EOS) visit i.e. up to 13 weeks (+10 days)
Population: Safety Population: The safety population included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INS018_055 30 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | Any TEAE | 13 Participants |
| INS018_055 30 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE with CTCAE grade ≥3 | 3 Participants |
| INS018_055 30 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to discontinuation of treatment | 1 Participants |
| INS018_055 30 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to death | 0 Participants |
| INS018_055 30 mg BID | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE with CTCAE grade ≥3 | 7 Participants |
| INS018_055 30 mg BID | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to discontinuation of treatment | 5 Participants |
| INS018_055 30 mg BID | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to death | 1 Participants |
| INS018_055 30 mg BID | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | Any TEAE | 15 Participants |
| INS018_055 60 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to discontinuation of treatment | 4 Participants |
| INS018_055 60 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE with CTCAE grade ≥3 | 8 Participants |
| INS018_055 60 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to death | 0 Participants |
| INS018_055 60 mg QD | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | Any TEAE | 15 Participants |
| Placebo | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to death | 0 Participants |
| Placebo | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE with CTCAE grade ≥3 | 4 Participants |
| Placebo | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | Any TEAE | 12 Participants |
| Placebo | Percentage of Participants Who Had at Least 1 Treatment-emergent Adverse Event (TEAE) | TEAE Leading to discontinuation of treatment | 2 Participants |
Secondary
Absolute Change From Baseline in FVC in L
Decline (change) in FVC is presented from Week 0 to Week 12. FVC was assessed using standardized spirometry equipment.
Time frame: Week 0/Visit 2 up to Week 12
Population: Intent-to-treat Population: The ITT population included any randomized participants. The ITT Population was used for summary of demographic and baseline characteristics, and it was used for analysis of secondary endpoints except PK analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INS018_055 30 mg QD | Absolute Change From Baseline in FVC in L | -0.0270 L | Standard Deviation 0.11368 |
| INS018_055 30 mg BID | Absolute Change From Baseline in FVC in L | 0.0197 L | Standard Deviation 0.14177 |
| INS018_055 60 mg QD | Absolute Change From Baseline in FVC in L | 0.0984 L | Standard Deviation 0.14113 |
| Placebo | Absolute Change From Baseline in FVC in L | -0.0203 L | Standard Deviation 0.183 |
95% CI: [-0.105, 0.0566]
95% CI: [-0.0687, 0.1074]
95% CI: [-0.0087, 0.1872]
95% CI: [-0.0981, 0.0817]
Secondary
Absolute Change in FVC % Predicted
Absolute change in FVC % predicted from Week 0 to Week 12 is presented. FVC was assessed using standardized spirometry equipment
Time frame: Week 0/Visit 2 up to Week 12
Population: Intent-to-treat Population: The ITT population included any randomized participant. The ITT Population was used for summary of demographic and baseline characteristics, and it was used for analysis of secondary endpoints except PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INS018_055 30 mg QD | Absolute Change in FVC % Predicted | -0.6729 Percent predicted | Standard Deviation 2.92554 |
| INS018_055 30 mg BID | Absolute Change in FVC % Predicted | 0.6455 Percent predicted | Standard Deviation 3.73482 |
| INS018_055 60 mg QD | Absolute Change in FVC % Predicted | 3.0461 Percent predicted | Standard Deviation 4.38853 |
| Placebo | Absolute Change in FVC % Predicted | -0.5675 Percent predicted | Standard Deviation 5.44712 |
95% CI: [-2.9549, 1.7462]
95% CI: [-1.9603, 3.2624]
95% CI: [-0.3187, 5.3136]
95% CI: [-2.8142, 2.7724]
Secondary
Relative Change From Baseline in Forced Vital Capacity (FVC)
Decline (change) in FVC is presented from Week 0 to Week 12. FVC was assessed using standardized spirometry equipment.
Time frame: Week 0/Visit 2 up to Week 12
Population: Intent-to-treat Population: The ITT population included any randomized participant. The ITT Population was used for summary of demographic and baseline characteristics, and it was used for analysis of secondary endpoints except PK analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INS018_055 30 mg QD | Relative Change From Baseline in Forced Vital Capacity (FVC) | -0.7923 percentage change in FVC | Standard Deviation 3.90508 |
| INS018_055 30 mg BID | Relative Change From Baseline in Forced Vital Capacity (FVC) | 0.6821 percentage change in FVC | Standard Deviation 6.09585 |
| INS018_055 60 mg QD | Relative Change From Baseline in Forced Vital Capacity (FVC) | 3.2253 percentage change in FVC | Standard Deviation 5.27457 |
| Placebo | Relative Change From Baseline in Forced Vital Capacity (FVC) | -0.7126 percentage change in FVC | Standard Deviation 8.17452 |
95% CI: [-4.1026, 2.8831]
95% CI: [-3.0738, 4.4179]
95% CI: [-1.697, 7.3433]
95% CI: [-4.5273, 3.9408]
Secondary
Relative Change in FVC % Predicted
Relative change in FVC % predicted from Week 0 to Week 12 is presented. FVC was assessed using standardized spirometry equipment
Time frame: Week 0/Visit 2 up to Week 12
Population: Intent-to-treat Population: The ITT population included any randomized participant. The ITT Population was used for summary of demographic and baseline characteristics, and it was used for analysis of secondary endpoints except PK analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INS018_055 30 mg QD | Relative Change in FVC % Predicted | -0.6724 Percent predicted | Standard Deviation 4.05537 |
| INS018_055 30 mg BID | Relative Change in FVC % Predicted | 0.4434 Percent predicted | Standard Deviation 5.96895 |
| INS018_055 60 mg QD | Relative Change in FVC % Predicted | 3.2194 Percent predicted | Standard Deviation 5.28129 |
| Placebo | Relative Change in FVC % Predicted | -0.8414 Percent predicted | Standard Deviation 8.31651 |
95% CI: [-4.0035, 2.8511]
95% CI: [-3.1449, 4.3216]
95% CI: [-1.8486, 7.1593]
95% CI: [-4.3227, 4.1977]