A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Systemic Sclerosis
Condition: Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: GLPG1690; Placebo
Intervention description: Film-coated tablets of GLPG1690 for oral use.; Film-coated tablets of GLPG1690 matching placebo for oral use.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of the study is to see if GLPG1690 helps (together with the standard of care
      treatment) in the treatment of the skin and other areas affected by systemic sclerosis.

      Another aim is to find out how safe/well tolerated GLPG1690 will be and whether there are any
      side effects. The study will also look at other things, including whether the study drug
      affects disease progression and also if it changes any aspect of the quality of life.
    

Eligibility criteria:

        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 participants ≥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.

          -  Modified Rodnan Skin Score (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).

          -  Participant must be able and willing to comply with restrictions on prior and
             concomitant medication as described in the protocol

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test at screening and a negative urine pregnancy test at the baseline visit.

          -  Female participants of childbearing potential or male participants 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 participants and 30 days after the last dose of the IMP
             for female participants.

          -  A body mass index (BMI) between 18-35 kg/m^2, 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 electrocardiogram (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 participant intending to become pregnant or breastfeed.

          -  History of or a current immunosuppressive condition (e.g. human immunodeficiency virus
             [HIV] infection, congenital, acquired).

          -  Positive blood testing for hepatitis B surface antigen or hepatitis C virus (antibody,
             confirmed by hepatitis C virus ribonucleic acid [RNA] positivity). Note: Participants
             with a resolved hepatitis A at least 3 months prior to screening can be screened.

          -  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 and
             ductal carcinoma in situ).

          -  Clinically significant abnormalities, in the opinion of the investigator, 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), in the opinion of the investigator, 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.