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

NCT02738801 | Completed Phase 2 Results DMC

• 2 other identifiers: GLPG1690-CL-2022015-004157-41
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 8

Brief Summary

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).

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis; GLPG1690; Autotaxin

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (2)

GLPG1690 600 mg once daily (QD)

EXPERIMENTAL

Drug: GLPG1690 600 mg QD

Placebo QD

PLACEBO COMPARATOR

Drug: Placebo QD

Interventions

GLPG1690 600 mg QD DRUG

GLPG1690 capsules, administered at a dose of 600 mg, orally QD

GLPG1690 600 mg once daily (QD)

Placebo QD DRUG

Matching placebo capsules, administered orally QD

Placebo QD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (8)

Municipal Clinical Hospital # 6

Dnipropetrovsk, Ukraine

Location

Kharkov City Clinical Hospital # 13

Kharkiv, Ukraine

Location

F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 1

Kiev, Ukraine

Location

F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 2

Kiev, Ukraine

Location

Oesa Regional Clinical Hospital

Odesa, Ukraine

Location

Poltava Regional Clinical Antituberculosis Dispancery

Poltava, Ukraine

Location

Royal Brompton Hospital

London, United Kingdom

Location

The Medicines Evaluation Unit

Manchester, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29792287 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

GLPG1690

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

None reported.

Results Point of Contact

• Title: Evelyn Fox
• Organization: Galapagos NV

evelyn.fox@glpg.com

003215342900

Study Officials

• Ann Fieuw, MD

  Galapagos NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2016
• First Posted: April 14, 2016
• Study Start: March 1, 2016
• Primary Completion: May 2, 2017
• Study Completion: May 2, 2017
• Last Updated: November 6, 2020
• Results First Posted: November 6, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

UA (6); GB (2)