Clinical trial NCT02738801: Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
GLPG1690
Autotaxin
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 23
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Treatment-Emergent Adverse Events (AEs)
timeFrame: From screening up to Day 98
measure: Mean Maximum Observed Plasma Concentration (Cmax; Micrograms Per Milliliter [µg/mL]) of GLPG1690
timeFrame: 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
measure: Median Time to Occurrence of GLPG1690 Cmax (Tmax; Hours [h])
timeFrame: 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
measure: Mean Area Under the Plasma Concentration-Time Curve (AUC[t]; µg.h/mL) of GLPG1690
timeFrame: 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
measure: Mean GLPG1690 Plasma Concentration Observed at Predose (Ctrough; µg/mL)
timeFrame: 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
measure: Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood
timeFrame: Baseline (Day -1), predose and 1.5 and 6 hours postdose on Day 28, predose on Day 84, and Day 98 (or early discontinuation)
measure: Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF)
timeFrame: Baseline (Day -1) and Day 84
Secondary outcomes:
Other outcomes:
Locations:
city: Dnipropetrovsk
country: Ukraine
facility: Municipal Clinical Hospital # 6
city: Kharkov
country: Ukraine
facility: Kharkov City Clinical Hospital # 13
city: Kiev
country: Ukraine
facility: F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 1
city: Kiev
country: Ukraine
facility: F.G. Yanovskyy Institute of Phthisiatry and Pulmonology 2
city: Odesa
country: Ukraine
facility: Oesa Regional Clinical Hospital
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Antituberculosis Dispancery
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit
Study officials:
affiliation: Galapagos NV
name: Ann Fieuw, MD
role: STUDY_DIRECTOR
References:
citation: 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.