Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic Pulmonary Fibrosis, GLPG1690, Autotaxin
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).
Interventions
DRUGGLPG1690 600 mg QD
GLPG1690 capsules, administered at a dose of 600 mg, orally QD
DRUGPlacebo QD
Matching placebo capsules, administered orally QD
Sponsors
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Day -1), predose and 1.5 and 6 hours postdose on Day 28, predose on Day 84, and Day 98 (or early discontinuation) | 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). |
| Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | Baseline (Day -1) and Day 84 | 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). |
Countries
Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo QD Participants received matching oral capsules QD for 12 weeks. | 6 |
| GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks. | 17 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo QD | GLPG1690 600 mg QD | Total |
|---|---|---|---|
| Age, Continuous | 64.0 years | 67.0 years | 66.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 17 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 17 |
| other Total, other adverse events | 4 / 6 | 11 / 17 |
| serious Total, serious adverse events | 2 / 6 | 1 / 17 |
Outcome results
Primary
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
Population: PK Analysis Population; excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Mean Area Under the Plasma Concentration-Time Curve (AUC[t]; µg.h/mL) of GLPG1690 | 55.6 µg.h/mL | Standard Deviation 46.6 |
Primary
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
Population: PK Analysis Population; excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Mean GLPG1690 Plasma Concentration Observed at Predose (Ctrough; µg/mL) | 0.624 µg/mL | Standard Deviation 0.846 |
Primary
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
Population: Pharmacokinetic (PK) Analysis Set: all randomized participants who received at least one dose of GLPG1690 and for whom evaluable PK data were available. Excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Mean Maximum Observed Plasma Concentration (Cmax; Micrograms Per Milliliter [µg/mL]) of GLPG1690 | 6.06 µg/mL | Standard Deviation 4.92 |
Primary
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
Population: PD Population; only patients with assessments at both baseline and the pre-specified visit were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | Day 84 | 0.0035 peak area ratio | Standard Error 0.0028 |
| Placebo QD | Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | Baseline | 0.0026 peak area ratio | Standard Error 0.0011 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | Day 84 | 0.0011 peak area ratio | Standard Error 0.0002 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) | Baseline | 0.0009 peak area ratio | Standard Error 0.0002 |
Primary
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)
Population: Pharmacodynamic (PD) Population: all randomized participants who received at least one dose of GLPG1690 and had at least one postbaseline assessment with PD data. Only patients with assessments at both baseline and the pre-specified visit(s) were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Baseline | 0.4180 peak area ratio | Standard Error 0.1088 |
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 | 0.3650 peak area ratio | Standard Error 0.0895 |
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 (1.5 hours postdose) | 0.4071 peak area ratio | Standard Error 0.1352 |
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 (6 hours postodse) | 0.3402 peak area ratio | Standard Error 0.1373 |
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 84 | 0.4080 peak area ratio | Standard Error 0.109 |
| Placebo QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 98 | 0.4672 peak area ratio | Standard Error 0.1647 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 84 | 0.0898 peak area ratio | Standard Error 0.016 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Baseline | 0.3311 peak area ratio | Standard Error 0.067 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 (6 hours postodse) | 0.0314 peak area ratio | Standard Error 0.0046 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 | 0.1476 peak area ratio | Standard Error 0.038 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 98 | 0.5172 peak area ratio | Standard Error 0.166 |
| GLPG1690 600 mg QD | Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood | Day 28 (1.5 hours postdose) | 0.0479 peak area ratio | Standard Error 0.012 |
Primary
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
Population: PK Analysis Population; excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo QD | Median Time to Occurrence of GLPG1690 Cmax (Tmax; Hours [h]) | 4 hours |
Primary
Number of Patients With Treatment-Emergent Adverse Events (AEs)
Time frame: From screening up to Day 98
Population: Safety Population: all randomized participants who received at least one dose of GLPG1690.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo QD | Number of Patients With Treatment-Emergent Adverse Events (AEs) | 4 Participants |
| GLPG1690 600 mg QD | Number of Patients With Treatment-Emergent Adverse Events (AEs) | 11 Participants |