Primary Objective-To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care compared to placebo in subjects with idiopathic pulmonary fibrosis (IPF) as evaluated by the rate of decline of forced vital capacity (FVC)…
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
Rate of decline of FVC (in mL) over a period of 52 weeks
Secondary outcome
Key Secondary Endpoints
- 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 at 52 weeks
- Time to first respiratory-related hospitalization until the end of the study
- Change from baseline in the SGRQ total score at 52 weeks
Background summary
GLPG1690 is a small-molecule autotaxin inhibitor targeting disease-relevant
signal transduction pathways, in clinical development for the treatment of
subjects with IPF.
Disease-modifying drugs such as pirfenidone and nintedanib have been shown to
have a beneficial effect on the rate of decline in lung function (as measured
by FVC over 1 year) and show a trend in favor of a reduction in mortality in
patients with mild to moderate IPF. However, the residual decline of FVC over
1 year remains substantial. Therefore, there remains a considerable unmet
medical need. In a proof-of-concept Phase 2a study, FVC values remained
stable in the majority of subjects after 12 weeks of treatment with
GLPG1690 600 mg once daily (q.d.). Moreover, 12 weeks of treatment with
GLPG1690 600 mg q.d. was generally well tolerated. The current Phase 3 study is
the next step in the clinical development of GLPG1690, evaluating the efficacy
and safety of two doses of orally administered GLPG1690 compared to placebo in
subjects with IPF in addition to local standard of care.
Study objective
Primary Objective
-To evaluate the efficacy of two doses of GLPG1690 in addition to local
standard of care compared to placebo in subjects with idiopathic pulmonary
fibrosis (IPF) as evaluated by the rate of decline of forced vital capacity
(FVC) over a period of 52 weeks
Secondary Objectives
Key Secondary Objectives
-To evaluate the impact of two doses of GLPG1690 in addition to local standard
of care compared to placebo in subjects with IPF on:
-disease progression defined as deterioration of FVC or all-cause
mortality at 52 weeks
-respiratory related hospitalization until the end of the study
-changes in quality of life (measured by St. George*s Respiratory
Questionnaire [SGRQ] total score) at 52 weeks
Study design
This clinical Phase 3 study is a randomized, double-blind, parallel-group,
placebo-controlled multicenter study designed to evaluate the efficacy and
safety of two doses of orally administered GLPG1690 in addition to local
standard of care for at least 52 weeks in adult subjects with a centrally
confirmed diagnosis of IPF. Local standard of care for IPF is defined as
receiving 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. Subjects will have their end
of study treatment (EoST) and follow-up visit planned when the last subject has
reached his or her Week 52 visit.
Intervention
GLPG1690 or placebo to match will be administered as film-coated tablets for
oral use once daily.
Following doses will be tested:
- GLPG1690 Dose A
- GLPG1690 Dose B
- Placebo to match"
Study burden and risks
Risks with GLPG1690
GLPG1690 has been tested in healthy volunteers and IPF subjects. GLPG1690 has
been found to be generally safe and well tolerated. The majority of reported
side effects from these studies have been mild in intensity. Side effects were
very similar as those found in subjects with IPF. Contact the investigator if
you develop:
- cough
- headache
- upper and lower respiratory tract infection
Risks and discomfort from procedures
* Blood collection: Collecting blood is normally done as part of routine
medical care and may cause some discomfort, bleeding, or bruising where the
needle enters the body. A small blood clot may form at this site or there may
be swelling in the area. Rarely, fainting or local infection may occur. Care
will be taken to prevent these events.
* High-resolution computed tomography (HRCT) if requested by your study
doctor. This procedure will expose the patient to a small amount of X-rays in
order to get a picture of their lungs. The total exposure will be equivalent to
approximately 2 years of natural background radiation in the environment.
During the scan, the patient will be asked to lie very still and sometimes you
will be asked to hold your breath. The patient should not move until the images
are taken (about 15 to 30 minutes). They may feel uncomfortable from this
immobilization.
* ECG: For ECGs collected in this study, the patient will have sticky
electrodes stuck to your chest, arms, and legs. The adhesive (sticky substance)
and gel found in the electrodes and adhesive pads can be irritating to their
skin, causing redness or itching. For male subjects, the study staff may also
have to shave small areas to make sure the electrodes stick properly to your
skin.
* Blood pressure: Although it is very rare, the patient might bruise from
having your blood pressure taken. In addition, the blood pressure cuff will be
very tight and might pinch a little for a short time.
* Lung function tests (spirometry and DLCO): Lung function tests may cause
light headedness, dizziness, tiredness, coughing, or shortness of breath. The
patient may experience some general chest discomfort from the deep breaths
required to perform these tests.
* 6 Minute Walk Test (6MWT): This test may cause light headedness, dizziness,
tiredness, coughing, or shortness of breath. The patient may experience some
general chest discomfort from the increased breathing required to walk for 6
minutes.
Benefit
The patient may or may not benefit from taking part in this study. If the
patient would benefit, their disease and decrease in lung function may progress
more slowly. Participating in clinical research studies like this may also give
the patient the opportunity to better understand your own disease and to have
more opportunities to talk and clarify any aspect of their disease. By
participating in this study, their condition will be closely monitored. In
addition, this study may be helpful in developing a new therapy for others with
similar illnesses.
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Generaal De Wittelaan L11 A3
Mechelen 2800
BE
Listed location countries
Age
Inclusion criteria
- Male or female subject aged *40 years on the day of signing the ICF.
- A diagnosis of IPF within 5 years prior to the screening visit, as per
applicable ATS/ERS/JRS/ALAT guidelinesat the time of diagnosis.
- Chest 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 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 at a stable dose for at least two months before
screening, and during screening; or nintedanib, 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, 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 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 6MWT at screening Visit 1;
without having a contraindication to perform the 6MWT (see Appendix 10) 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 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 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 antibiotics within 4 weeks prior to screening and/or during
the screening period.
- Lower respiratory tract infection requiring antibiotics 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 (investigatordetermined).
- 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 >5xULN and
increased susceptibility to elevated LFT; moderate to severe hepatic impairment
(Child-Pugh B or C) and/or abnormal LFT at screening, defined as AST, and/or
ALT, and/or total bilirubin *1.5xULN, and/or GGT *3xULN. 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.
- Clinical laboratory test suggestive of cholestasis with total serum bile
acid levels >3xULN.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001406-29-NL |
| ClinicalTrials.gov | NCT03733444 |
| CCMO | NL67478.078.18 |