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A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care (ISABELA2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03733444
Recruitment Status : Terminated (The benefit-risk profile no longer supports continuing the study)
First Posted : November 7, 2018
Results First Posted : July 29, 2022
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
Galapagos NV

Brief Summary:
The main purpose of this study was to see how GLPG1690 works together with the 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 get any side effects while on study drug).

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: GLPG1690 Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 781 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Two Doses of GLPG1690 in Addition to Local Standard of Care for Minimum 52 Weeks in Subjects With Idiopathic Pulmonary Fibrosis
Actual Study Start Date : November 5, 2018
Actual Primary Completion Date : March 30, 2021
Actual Study Completion Date : March 30, 2021


Arm Intervention/treatment
Experimental: GLPG1690, 600 milligrams (mg)
Participants received GLPG1690 (ziritaxestat) 600 mg as film-coated tablet orally, once daily (mean treatment duration was 332.9 days). Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
Drug: GLPG1690
GLPG1690, film-coated tablets for oral use.
Other Name: ziritaxestat

Experimental: GLPG1690, 200 mg
Participants received GLPG1690 (ziritaxestat) 200 mg as film-coated tablet orally, once daily (mean treatment duration was 336.9 days). Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
Drug: GLPG1690
GLPG1690, film-coated tablets for oral use.
Other Name: ziritaxestat

Experimental: Placebo
Participants received GLPG1690 (ziritaxestat) matching placebo tablets orally, once daily (mean treatment duration was 346.2 days). Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
Drug: Placebo
Matching placebo, film-coated tablets for oral use.




Primary Outcome Measures :
  1. Annual Rate of Decline in Forced Vital Capacity (FVC) up to Week 52 [ Time Frame: Baseline 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Disease Progression Up to 52 Weeks [ Time Frame: 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.

  2. Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS) [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with respiratory related to hospitalization were reported in this measure.

  3. Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52 [ Time Frame: Baseline, 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.


  4. Annual Rate of Decline of FVC Until EoS [ Time Frame: Baseline up to EoS (week 125) ]
    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.

  5. Percentage of Participants With Disease Progression Until EoS [ Time Frame: Up to EoS (week 125) ]
    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.

  6. Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 100 [ Time Frame: Baseline, week 100 ]

    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.


  7. Percentage of Participants With All Cause Hospitalization Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with all cause hospitalization was reported for this measure.

  8. Percentage of Participants With Respiratory Related Mortality Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with respiratory related mortality until end of study were reported for this study.

  9. Percentage of Participants Hospitalized for Non-Elective Lung Transplant Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of Participants who were hospitalized for lung transplant were reported for this measure.

  10. Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with acute IPF exacerbation until end of study were reported for this measure.

  11. Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with all-cause mortality or hospitalization for non-elective lung transplant were reported for this measure.

  12. Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with all-cause mortality or hospitalization for qualifying for lung transplant were reported for this measure.

  13. Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS [ Time Frame: Up to EoS (week 125) ]
    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.

  14. Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS [ Time Frame: Up to EoS (week 125) ]
    Percentage of participants with all-cause mortality or respiratory related hospitalization were reported for this measure.

  15. FVC at Week 52 [ Time Frame: 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.

  16. Change From Baseline in FVC at Week 52 [ Time Frame: Baseline, 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.

  17. Percent Change From Baseline in FVC at Week 52 [ Time Frame: Baseline, 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.

  18. FVC at Week 100 [ Time Frame: Week 100 ]
    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.

  19. Change From Baseline in FVC at Week 100 [ Time Frame: Baseline, week 100 ]
    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.

  20. Percent Change From Baseline in FVC at Week 100 [ Time Frame: Baseline, week 100 ]
    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.

  21. Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5 [ Time Frame: Baseline, 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.

  22. Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: FVC Change Within ≤5 [ Time Frame: Baseline, week 100 ]
    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.

  23. Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10 [ Time Frame: Baseline, 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.

  24. Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 100: FVC Change Within ≤10 [ Time Frame: Baseline, week 100 ]
    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.

  25. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Baseline up to EoS (up to Week 125) ]
    Safety was assessed by adverse events (AEs), which included abnormalities identified during a medical test (e.g. 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.

  26. Changes From Baseline in Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    Cough was evaluated using the LCQ. The LCQ is a 19-item questionnaire split into three domains: physical, psychological, and social. Scores were calculated by domain (range from 1 to 7) 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.

  27. Changes From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    Cough was assessed using VAS score, ranged from 0 (no cough) to 100 millimeter (mm) (worst possible cough).

  28. Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    Urge to Cough was assessed using VAS score, ranged from 0 (no urge to cough) to 100 mm (highest urge to cough).

  29. Changes From Baseline in EuroQOL 5-Dimensions Questionnaire at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    EuroQol outcome measurements was a printed 20 centimeter (cm) EQ visual analogue scale (EQ 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.

  30. Changes From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    The King's Brief Interstitial Lung Disease questionnaire (K-BILD) was specifically developed to analyze the health status of participants with OLD, the questionnaire consists of of 15 items (assessed by participants on scale ranging from 1 to 7, where 1 and 7 represents 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).

  31. Area Under The Concentration Time Curve of Ziritaxtestat [ 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 ]
    Area under the concentration time curve of ziritaxtestat was reported

  32. Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat [ 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 of Ziritaxtestat was reported.

  33. Change From Baseline in Functional Exercise Capacity, Assessed by The 6-Minute Walk Test (6MWT) Distance, at Week 52 and Week 100 [ Time Frame: Baseline, week 52, week 100 ]
    The 6MWT depicts the total distance covered by a participant during 6 minutes walking.

  34. Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100 [ Time Frame: Baseline, week 52 and week 100 ]

    Change from baseline in diffusing capacity of the lung for carbon monoxide (percent predicted hemoglobin level corrected) was reported for this measure.

    mmol/min/kPa: Millimole per minute per kilopascal




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03733444


Locations
Show Show 132 study locations
Sponsors and Collaborators
Galapagos NV
Investigators
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Study Director: Galapagos Study Director Galapagos NV
  Study Documents (Full-Text)

Documents provided by Galapagos NV:
Study Protocol  [PDF] June 8, 2020
Statistical Analysis Plan  [PDF] March 25, 2021

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Galapagos NV
ClinicalTrials.gov Identifier: NCT03733444    
Other Study ID Numbers: GLPG1690-CL-304
2018-001406-29 ( EudraCT Number )
First Posted: November 7, 2018    Key Record Dates
Results First Posted: July 29, 2022
Last Update Posted: July 29, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases