A Clinical Study to Test How Effective and Safe GLPG1690 is for Patients With Systemic Sclerosis

Inclusion Criteria:

- Able and willing to comply with the protocol requirements and to sign the informed
consent form (ICF) as approved by the Independent Ethics Committee (IEC)/Institutional
Review Board (IRB), prior to any screening evaluations.

- Male and female subjects ≥18 years at the time of consent who meet the American
College of Rheumatology (ACR)/EULAR 2013 diagnostic criteria for systemic sclerosis
with diffuse cutaneous involvement (according to LeRoy's criteria) and ≤5 years since
the onset of the first systemic sclerosis manifestation other than Raynaud's
phenomenon.

- mRSS >10 at screening.

- Active disease at screening, as defined by: Worsening of skin thickening (≥2 mRSS
points) as assessed by mRSS measured at screening versus a previous mRSS assessment
made within 6 months prior to screening, or new areas of skin involvement within 6
months prior to screening as documented by physician note, or new-onset systemic
sclerosis with symptoms or signs other than Raynaud's phenomenon within 2 years prior
to screening, or ≥1 tendon friction rub (palpated in the finger flexors or extensors,
wrist flexors or extensors, olecranon bursa, shoulders, knees, anterior or posterior
ankles with active motion).

- Subject must be able and willing to comply with restrictions on prior and concomitant
medication as described in the protocol

- Female subjects of childbearing potential must have a negative serum pregnancy test at
screening.

- Female subjects of childbearing potential or male subjects with female partners of
childbearing potential must be willing to comply with the contraceptive methods
described in the protocol prior to the first dose of the investigational medicinal
product (IMP), during the clinical study, and for at least 90 days after the last dose
of the IMP for male subjects and 30 days after the last dose of the IMP for female
subjects.

- A body mass index (BMI) between 18-35 kg/m2, inclusive, at screening.

- Judged to be in good health by the investigator based upon the results of a medical
history, physical examination, vital signs, 12-lead ECG, and fasting clinical
laboratory safety tests. Clinical laboratory safety test results must be within the
reference ranges or test results that are outside the reference ranges need to be
considered non-clinically significant in the opinion of the investigator.

Exclusion Criteria:

- Known hypersensitivity to IMP ingredients or history of a significant allergic
reaction to any drug as determined by the investigator, such as anaphylaxis requiring
hospitalization.

- Breastfeeding female or subject intending to become pregnant or breastfeed.

- History of or a current immunosuppressive condition (e.g. human immunodeficiency virus
[HIV] infection, congenital, acquired).

- Positive serology for hepatitis B (surface antigen) or C (antibody), or any history of
hepatitis from any cause. For hepatitis A, a history of infection within 12 weeks
prior to screening. Positive serology for HIV-1 and HIV-2 (antibodies).

- 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 medically managed through active surveillance
or watchful waiting, and squamous cell carcinoma of the skin if fully resected).

- Clinically significant abnormalities detected on ECG at screening of either rhythm or
conduction, QT interval corrected for heart rate using Fridericia's formula (QTcF)
>450 ms, or a known long QT syndrome.

- Unstable cardiovascular, pulmonary, or other disease (other than systemic
sclerosis-related) within 6 months prior to the baseline visit (e.g. coronary heart
disease, heart failure, stroke).

- Severe pulmonary disease with forced vital capacity (FVC) ≤45% of predicted within 6
months prior to the baseline visit.

- Chronic or ongoing active infectious disease, including tuberculosis (requiring
hospitalization or systemic treatment within 4 weeks prior to the baseline visit).

- Abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase
(AST), and/or alanine aminotransferase (ALT), and/or bilirubin, and/or alkaline
phosphatase >2x upper limit of normal (ULN). Retesting is allowed once.