A Clinical Study to Test How Effective and Safe GLPG1690 is for Subjects With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care

Phase 3TerminatedNCT03711162

Galapagos NV525 enrolled

Overview

The main purpose of this study was to see how GLPG1690 works together with your current standard treatment on your lung function and IPF disease in general. The study also investigated how well GLPG1690 is tolerated (for example if you got any side effects while on study drug).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

525

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

GLPG1690DRUG

GLPG1690, film-coated tablets for oral use.

PlaceboDRUG

Matching placebo, film-coated tablets for oral use.

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female subject aged ≥40 years on the day of signing the Informed Consent Form (ICF). * A diagnosis of IPF within 5 years prior to the screening visit, as per applicable American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines at the time of diagnosis. * Chest high-resolution computed tomography (HRCT) historically performed within 12 months prior to the screening visit and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy (LB) available), or based on both HRCT and LB (with application of the different criteria in either situation). If an evaluable HRCT \<12 months prior to screening is not available, an HRCT can be performed at screening to determine eligibility, according to the same requirements as the historical HRCT. * Subjects receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least two months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). A stable dose is defined as the highest dose tolerated by the subject during those two months. * The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator-determined). * Meeting all of the following criteria during the screening period: FVC ≥45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hb ≥30% predicted of normal. * Estimated minimum life expectancy of at least 30 months for non IPF related disease in the opinion of the investigator. * Male subjects and female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of investigational medicinal product (IMP) (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days (male) or 30 days (female) after the last dose of IMP. * Able to walk at least 150 meters during the 6-Minute Walk Test (6MWT) at screening Visit 1; without having a contraindication to perform the 6MWT or without a condition putting the subject at risk of falling during the test (investigator's discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any condition. At Visit 2, for the oxygen titration test, resting oxygen saturation (SpO2) should be ≥88% with maximum 6 L O2/minute; during the walk, SpO2 should be ≥83% with 6 L O2/minute or ≥88% with 0, 2 or 4 L O2/minute. Exclusion Criteria: * History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal Carcinoma In Situ). * Clinically significant abnormalities detected on ECG of either rhythm or conduction, a QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 ms, or a known long QT syndrome. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the study based upon investigator judgment following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor. * Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically \< 1 month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure or fluid overload. * Lower respiratory tract infection requiring treatment within 4 weeks prior to screening and/or during the screening period. * Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs (e.g. amiodarone). * Diagnosis of severe pulmonary hypertension (investigator- determined). * Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period (e.g. acute coronary disease, heart failure, and stroke). * Had gastric perforation within 3 months prior to screening or during screening, and/or underwent major surgery within 3 months prior to screening, during screening or have major surgery planned during the study period. * History of nintedanib-related increase in ALT and/or AST of \>5 x upper limit of the normal range (ULN) and increased susceptibility to elevated LFT; moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or total bilirubin ≥1.5 x upper limit of the normal range (ULN), and/or gamma glutamyl transferase (GGT) ≥3 x ULN. Retesting is allowed once for abnormal LFT. * Abnormal renal function defined as estimated creatinine clearance, calculated according to Cockcroft-Gault calculation (CCr) \<30 mL/min. Retesting is allowed once. * Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose \>10 mg/day or equivalent.

Locations (132)

Outcomes

Primary Outcomes

Annual Rate of Decline in FVC up to Week 52

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline up to week 52

Secondary Outcomes

Percentage of Participants With Disease Progression up to Week 52

Disease progression was defined as the composite occurrence of more than or equal to (\>=)10 percent (%) absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Up to week 52

Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)

Percentage of participants with respiratory related hospitalization were reported in this measure.

Time frame: Up to EoS (week 121)

Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52

SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms score assessing the frequency and severity of respiratory symptoms (Items 1-8), activity score assessing the effects of breathlessness on mobility and physical activity (Items 11-17 and 36 to 44), and impacts score assessing the psychosocial impact of the disease (Items 9-10, 18-35 and 45-50). Each item has a specific weight. Domain scores = 100 \* summed weights from positive items in that component/sum of maximum weights for all non-missing items in that component Total score = 100 \* summed weights from positive items in the questionnaire/sum of maximum weights for all non-missing items in the questionnaire Scores were weighted such that each domain score ranged from 0 to 100 and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL.

Data from ClinicalTrials.gov

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Pulmonary Associates

Phoenix, Arizona, United States

Mayo Clinic Arizona - PPDS

Scottsdale, Arizona, United States

Atria Clinical Research - BTC - PPDS

Little Rock, Arkansas, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Respire Research

Palm Springs, California, United States

University of California San Diego

San Diego, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Colorado

Aurora, Colorado, United States

National Jewish Health

Denver, Colorado, United States

Western Connecticut Medical Group

Danbury, Connecticut, United States

...and 122 more locations

Time frame: Baseline, week 52

Annual Rate of Decline in FVC Until EoS

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline up to EoS (week 121)

Percentage of Participants With Disease Progression Until EoS

Disease progression was defined as the composite occurrence of \>=10% absolute decline in percent predicted %FVC or all-cause mortality. FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Up to EoS (week 121)

Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100

Time frame: Baseline, week 100

Percentage of Participants With All Cause Hospitalization Until EoS

Percentage of participants with all cause hospitalization was reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With Respiratory Related Mortality Until EoS

Percentage of participants with respiratory related mortality until EoS were reported for this study.

Time frame: Up to EoS (week 121)

Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS

Percentage of Participants who were hospitalized for Non-elective lung transplant were reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS

Percentage of participants with acute IPF exacerbation until EoS were reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS

Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant were reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS

Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant or hospitalization for qualifying for lung transplant were reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS

Percentage of participants with all-cause mortality or respiratory related hospitalization that meets \>=10% absolute decline in %FVC or respiratory-related hospitalization were reported for this measure.

Time frame: Up to EoS (week 121)

Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS

Percentage of participants with all-cause mortality or respiratory related hospitalization were reported for this measure.

Time frame: Up to EoS (week 121)

FVC at Week 52

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Week 52

Change From Baseline in FVC at Week 52

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 52

Percent Change From Baseline in FVC at Week 52

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 52

FVC at Week 112

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Week 112

Change From Baseline in FVC at Week 112

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 112

Percent Change From Baseline in FVC at Week 112

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 112

Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 52

Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤5

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 112

Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 52

Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤10

FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Time frame: Baseline, week 112

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

Safety was assessed by AEs, which included abnormalities identified during a medical test (example, laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A Treatment emergent AE (TEAE) was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

Time frame: Baseline up to 30 days after the last dose (up to week 121)

Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100

Cough was evaluated using the LCQ. The LCQ was a 19-item questionnaire split into three domains: physical, psychological, and social. Scores were calculated by domain (range from 1 to 7, higher scores indicated a better health status) and then the total score was calculated by adding the individual domain score. Total score ranged from 3 to 21, with higher scores indicated a better health status.

Time frame: Baseline, week 52, week 100

Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100

Cough was assessed using VAS score, ranged from 0 (no cough) to 100 millimeter (mm) (worst possible cough).

Time frame: Baseline, week 52, week 100

Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100

Urge to Cough was assessed using VAS score, ranged from 0 (no urge to cough) to 100 mm (highest urge to cough).

Time frame: Baseline, week 52, week 100

Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100

EuroQol outcome measurements is a printed 20 cm VAS that appears somewhat like a thermometer, on which a score from 0 (worst imaginable health state or death) to 100 (best imaginable health state) was marked by the participant (or, when necessary, their proxy) with the scale in view.

Time frame: Baseline, week 52, week 100

Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100

The K-BILD questionnaire was specifically developed to analyze the health status of participants with ILD. The questionnaire consists of 15 items (assessed by the participants on a scale ranging from 1 to 7, where 1 and 7 represent worst and best health status). Items are compiled into 3 domains: breathlessness and activities (range: 0-21), psychological (range: 0-34) , and chest symptoms (range: 0-8). To score the K-BILD, the Likert response scale weightings for individual items are combined and scores are transformed to a range of 0-100 by using logit values (higher scores indicate better health status).

Time frame: Baseline, week 52, week 100

Area Under The Concentration Time Curve (AUC) of Ziritaxtestat

Area under the concentration time curve of ziritaxtestat was reported.

Time frame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose

Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat

Maximum Observed Plasma Concentration of Ziritaxtestat was reported.

Time frame: Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose

Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100

The 6-MWT depicted the total distance covered by a participant during 6 minutes of walking.

Time frame: Baseline, week 52, week 100

Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100

Change from baseline in DLCO (percent predicted hemoglobin level corrected) was reported for this measure.mmol/min/kPa: Millimole per minute per kilopascal

Time frame: Baseline, week 52, week 100