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

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)

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).

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: GLPG1690 600 mg QD; Drug: Placebo QD

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ukraine
  • Dnipropetrovsk, Ukraine
    • Municipal Clinical Hospital # 6
  • Kharkov, Ukraine
    • Kharkov City Clinical Hospital # 13
  • Kiev, Ukraine
    • F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 1
  • Kiev, Ukraine
    • F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 2
  • Odesa, Ukraine
    • Oesa Regional Clinical Hospital
  • Poltava, Ukraine
    • Poltava Regional Clinical Antituberculosis Dispancery
• United Kingdom
  • London, United Kingdom
    • Royal Brompton Hospital
  • Manchester, United Kingdom
    • The Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects able and willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF)
2. Male or female subjects of non-child-bearing potential aged ≥ 40 years
3. Subjects with a chest HRCT performed within 12 months prior to screening
4. Subjects with IPF diagnosed by a multidisciplinary team
5. 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
6. Subjects with a forced expiratory volume in 1 second (FEV1)/FVC (Tiffeneau-Pinelli index) ratio ≥ 0.70 (based on pre-bronchodilator spirometry
7. Subjects on stable supportive care
8. Subjects in stable condition

Exclusion Criteria:

1. Subjects with know hypersensitivity to any of the study drug ingredients
2. Subjects with a history of or current immunosuppressive condition
3. Subjects with a history of malignancy within the past 5 years
4. Subjects with clinically significant abnormalities on ECG
5. Subjects with acute IPF exacerbation within 6 weeks prior to screening
6. Subjects with a lower respiratory tract infection requiring antibiotics with 4 weeks prior to screening
7. Smoking within 3 months pre-screening
8. Interstitial lung disease
9. History of lung volume reduction surgery or lung transplant
10. Unstable cardiac or pulmonary disease other than IPF within 6 months prior to screening
11. Subjects with abnormal liver function
12. Subjects with abnormal renal function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Ann Fieuw, MD, Galapagos NV

Publications and helpful links

General Publications

• Maher TM, van der Aar EM, Van de Steen O, Allamassey L, Desrivot J, Dupont S, Fagard L, Ford P, Fieuw A, Wuyts W. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir Med. 2018 Aug;6(8):627-635. doi: 10.1016/S2213-2600(18)30181-4. Epub 2018 May 20.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): May 2, 2017
• Study Completion (Actual): May 2, 2017

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimate): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): November 6, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; Autotaxin; GLPG1690
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: GLPG1690-CL-202; 2015-004157-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No