Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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A multicenter randomized, double-blind, parallel group, placebo-controlled, exploratory phase IIa study in subjects with Idiopathic Pulmonary Fibrosis (IPF) to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG1690. Male and female subjects aged 40 years or older will be screened to determine eligibility. The screening period will be up to 4 weeks. At baseline, eligible subjects will be randomized in a 3:1 ratio to GLPG1690 or matching placebo administered for 12 weeks. The subjects will visit the study center at screening, baseline, Weeks 1, 2, 4, 8 and 12 and for a follow-up visit 2 weeks after the last administration of study drug. Planned assessments: Adverse event reporting, clinical laboratory tests, vital signs, physical examination, 12-Lead-ECG, PK blood sampling, biomarker blood/bronchoalveolar lavage fluid (BALF), Spirometry, St George's respiratory questionnaire, high-resolution computed tomography (HRCT).

Official Title
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Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Multicenter, Exploratory Phase IIa Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Administered for 12 Weeks in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: GLPG1690 600 mg QD
* Drug: Placebo QD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects able and willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) Male or female subjects of non-child-bearing potential aged ≥ 40 years Subjects with a chest HRCT performed within 12 months prior to screening Subjects with IPF diagnosed by a multidisciplinary team Subjects with: a. forced vital capacity (FVC) ≥50% predicted of normal AND b. Diffusing capacity for the lungs for carbon monoxide (DLCO) ≥ 30% predicted of normal corrected for hemoglobin Subjects with a forced expiratory volume in 1 second (FEV1)/FVC (Tiffeneau-Pinelli index) ratio ≥ 0.70 (based on pre-bronchodilator spirometry Subjects on stable supportive care Subjects in stable condition Exclusion Criteria: Subjects with know hypersensitivity to any of the study drug ingredients Subjects with a history of or current immunosuppressive condition Subjects with a history of malignancy within the past 5 years Subjects with clinically significant abnormalities on ECG Subjects with acute IPF exacerbation within 6 weeks prior to screening Subjects with a lower respiratory tract infection requiring antibiotics with 4 weeks prior to screening Smoking within 3 months pre-screening Interstitial lung disease History of lung volume reduction surgery or lung transplant Unstable cardiac or pulmonary disease other than IPF within 6 months prior to screening Subjects with abnormal liver function Subjects with abnormal renal function

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG1690 600 mg once daily (QD)<br> | Drug: GLPG1690 600 mg QD<br>* GLPG1690 capsules, administered at a dose of 600 mg, orally QD<br>|
| Placebo Comparator: Placebo QD<br> | Drug: Placebo QD<br>* Matching placebo capsules, administered orally QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment-Emergent Adverse Events (AEs) |  | From screening up to Day 98 | 
| Mean Maximum Observed Plasma Concentration (Cmax; Micrograms Per Milliliter [µg/mL]) of GLPG1690 |  | Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28 | 
| Median Time to Occurrence of GLPG1690 Cmax (Tmax; Hours [h]) |  | Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28 | 
| Mean Area Under the Plasma Concentration-Time Curve (AUC[t]; µg.h/mL) of GLPG1690 |  | Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28 | 
| Mean GLPG1690 Plasma Concentration Observed at Predose (Ctrough; µg/mL) |  | Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28 | 
| Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | LPA species C18:2 concentrations were determined in blood using a validated liquid chromatography tandem mass spectometry (LC/MS-MS) method. The baseline reference timepoint was Day -1 (mean of the pre-dosing duplicates). | Baseline (Day -1), predose and 1.5 and 6 hours postdose on Day 28, predose on Day 84, and Day 98 (or early discontinuation) | 
| Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | LPA species C18:2 concentrations were determined in BALF using a validated LC/MS-MS method. The baseline reference timepoint was Day -1 (mean of the pre-dosing duplicates). | Baseline (Day -1) and Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Pulmonary Fibrosis, GLPG1690, Autotaxin