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

Lakefront Biotherapeutics NV23 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Locations (8)

Municipal Clinical Hospital # 6

Dnipropetrovsk, Ukraine

Kharkov City Clinical Hospital # 13

Kharkiv, Ukraine

F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 1

Kiev, Ukraine

F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 2

Kiev, Ukraine

Oesa Regional Clinical Hospital

Odesa, Ukraine

Poltava Regional Clinical Antituberculosis Dispancery

Poltava, Ukraine

Royal Brompton Hospital

London, United Kingdom

The Medicines Evaluation Unit

Manchester, United Kingdom

Outcomes

Primary Outcomes

Number of Patients With Treatment-Emergent Adverse Events (AEs)

Time frame: From screening up to Day 98

Mean Maximum Observed Plasma Concentration (Cmax; Micrograms Per Milliliter [µg/mL]) of GLPG1690

Time frame: 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])

Time frame: 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

Time frame: 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)

Time frame: 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).

Time frame: 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).

Time frame: Baseline (Day -1) and Day 84