A Clinical Study to Test How Effective and Safe GLPG1205 is for Participants With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blind, parallel-group, placebo-controlled, multicenter, exploratory Phase 2 study including participants with Idiopathic Pulmonary Fibrosis (IPF), investigating GLPG1205 in addition to the local standard of care (defined as receiving nintedanib, pirfenidone, or neither nintedanib nor pirfenidone).

Official Title
-----------------
A Phase II Randomized, Double-blind, Placebo-controlled, 26-week Study to Evaluate the Efficacy, Safety and Tolerability of GLPG1205 in Subjects With Idiopathic Pulmonary Fibrosis

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: GLPG1205
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Participants who meet all of the following criteria are eligible for the study: A diagnosis of IPF within 5 years prior to the screening visit as per applicable American Thoracic Society (ATS)/European Respiratory Society(ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guideline. Participants receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least 8 weeks before screening, and during screening; or neither pirfenidone nor nintedanib (for any reason). A stable dose is defined as the highest tolerated dose. Prednisone at steady dose less than or equal to 10 mg/day or equivalent glucocorticoid dose is allowed (stabilized 4 weeks prior to screening and continued without variation of dose or regimen). Supportive care like supplemental oxygen or pulmonary rehabilitation is allowed. Meeting all of the following criteria at screening and during the screening period: Forced vital capacity (FVC) greater than or equal to 50% predicted of normal Disease progression, defined as a decline of FVC (% predicted or milliliters [mL]) at the investigator's discretion, during the 9 months prior to the screening period and confirmed at the screening visit Diffusing capacity for the lungs for carbon monoxide (DLCO) greater than or equal to 30% predicted of normal (corrected for hemoglobin) Ratio of forced expiratory volume in one second (FEV1) to FVC greater than or equal to 0.70 In a stable condition and suitable for study participation based on the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and laboratory evaluation. Stable condition is based on the clinical judgment of the investigator, co-morbidities should be treated according to the local applicable guidelines. Concomitant medication for chronic comorbidities should be stabilized from 4 weeks before screening and during the screening period (stable defined as no clinically relevant change according to the investigator's judgement). Able to walk at least 150 meters during the 6 Minute Walk Test (6MWT) at screening; without having a contraindication to perform the 6MWT. This list only describes the key inclusion criteria. Exclusion criteria: Participants meeting one or more of the following criteria cannot be selected for this study: Known hypersensitivity to any of the investigational medicinal product (IMP) ingredients or a history of a significant allergic reaction to any drug as determined by the investigator (e.g. anaphylaxis requiring hospitalization). Current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection, congenital, acquired, medication induced, organ transplantation). Positive blood testing for hepatitis B surface antigen (HBS Ag) or hepatitis C virus (HCV) antibody (if positive, confirmed by HCV ribonucleic acid [RNA] positivity). Note: Participants with a resolved hepatitis A at least 3 months prior to first dosing of the IMP can be included. History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, and prostate cancer medically managed through active surveillance or watchful waiting, and squamous cell carcinoma of the skin if fully resected). Acute IPF exacerbation within 3 months prior to screening and during the screening period. Lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and/or during the screening period. Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis, amyloidosis), exposures (e.g. radiation, silica, asbestos, coal dust), and drugs (e.g. amiodarone). History of lung volume reduction surgery or lung transplant. Unstable cardiovascular, pulmonary (other than IPF) or other disease within 6 months prior to screening or during the screening period (e.g. coronary heart disease, heart failure, stroke). Participant participating in a drug, device or biologic investigational research study, concurrently with the current study, within 12 weeks or 5-half-lives of the agent, whichever is longer, prior to screening, or prior participation in an investigational drug antibody/biologic study within 6 months prior to screening. This list only describes the key exclusion criteria.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG1205 100 mg<br>Participants will receive GLPG1205 100 milligrams (mg) (2 capsules x 50 mg), orally once daily for 26 weeks in addition to the local standard of care. Standard of care includes nintedanib, pirfenidone, or neither nintedanib nor pirfenidone. | Drug: GLPG1205<br>* GLPG1205 will be provided as an oral hard gelatin capsule.<br>|
| Placebo Comparator: Placebo<br>Participants will receive GLPG1205 matching placebo, orally once daily (as 2 capsules) for 26 weeks in addition to the local standard of care. Standard of care includes nintedanib, pirfenidone, or neither nintedanib nor pirfenidone. | Drug: Placebo<br>* GLPG1205 matching placebo will be provided as an oral hard gelatin capsule.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 26 | Forced vital capacity (FVC) (in milliliter [mL]) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Related to Study Drug, and TEAEs Leading to Study Drug Discontinuation | An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. A TEAE was any AE with an onset date on or after the start of study drug intake and no later than 30 days after last dose of study drug, or any worsening of any AE on or after the start of study drug intake. A serious AE was defined as an AE that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically significant. | First dose date up to 30 days after the last dose of study drug (maximum up to 263 days) | 
| Time to Any Major Events Depicted by Cumulative Percentage of Participants With All-cause Deaths, Respiratory-related Deaths, All-cause Hospitalizations, and Respiratory-related Hospitalizations | Treatment effect on time to death (all-cause and respiratory-related)/hospitalization (all-cause and respiratory-related) were assessed using the log-rank test. Kaplan-Meier estimates were derived for the probability of death (all-cause and respiratory-related)/hospitalization (all-cause and respiratory-related). Cumulative percentage of participants with all-cause deaths, respiratory-related deaths, all-cause hospitalizations, and respiratory-related hospitalizations were reported. | Day 1 up to Week 30 | 
| Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 26 | The 6-MWT depicts the total distance covered by a participant during 6 minutes of walking. | Baseline, Week 26 | 
| Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 26 | The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. | Baseline, Week 26 | 
| Change From Baseline in SGRQ Domain Score at Week 26 | The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related QOL and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. | Baseline, Week 26 | 
| Percentage of SGRQ Responders | The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related QOL and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score and total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. SGRQ responders are those with absolute change from baseline in SGRQ total score less than or equal to -4 percent (%) at least once. | Baseline up to Week 26 | 
| Pre-dose Plasma Concentration (Ctrough) of GLPG1205 at Week 26 | GLPG1205 pre-dose plasma concentration (Ctrough) at Week 26 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged). | Week 26 (pre-dose) | 
| Pre-dose Plasma Concentration (Ctrough) of Nintedanib at Week 20 | Nintedanib pre-dose plasma concentration (Ctrough) at Week 20 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged). | Week 20 (pre-dose) | 
| Pre-dose Plasma Concentration (Ctrough) of Pirfenidone at Week 20 | Pirfenidone pre-dose plasma concentration (Ctrough) at Week 20 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged). | Week 20 (pre-dose) |