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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 May 2021
• Main ID: NCT03733444
• Date of registration: 05/11/2018
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: 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 ISABELA2
• Scientific 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
• Date of first enrolment: November 5, 2018
• Target sample size: 781
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03733444
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Canada, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, South Africa, United States

Contacts

• Name: Tomasz Masior, MD
• Affiliation: Galapagos NV

Key inclusion & exclusion 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.



Age minimum: 40 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: GLPG1690

Drug: Placebo

Primary Outcome(s)

Rate of decline of forced vital capacity (FVC) in mL. [Time Frame: From baseline through week 52]

Secondary Outcome(s)

Disease progression defined as the composite endpoint of first occurrence of =10% absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality. [Time Frame: At week 52]

Time to first respiratory-related hospitalization until the end of the study. [Time Frame: From screening through study completion, a minimum of 52 weeks]

Change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score. [Time Frame: At week 52]

Secondary ID(s)

2018-001406-29

GLPG1690-CL-304

Source(s) of Monetary Support

Please refer to primary and secondary sponsors