| 1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
2. Patients must be at least 18 years of age and fulfil the 2013 ACR/EULAR criteria for SSc.
3. Patients must be diagnosed with lcSSc or dcSSc, as defined by LeRoy et al.
4. Disease onset (defined by first non-RP [Raynaud’s phenomenon] symptom) must be within 7 years of Visit 1.
5. Trial participants with dcSSc must have evidence of active disease during screening. Active disease is defined as having at least one of the following:
a) New onset of SSc (defined by first non-RP symptom) within the last 2 years of Visit 1, OR
b) New skin involvement or worsening of 2 new body areas within 6 months of Visit 1 (out of the 17 body areas defined by mRSS assessment, documented in clinical files), OR
c) New or worsening skin involvement of either chest or abdomen within 6 months of Visit 1, OR
d) Worsening of skin thickening defined as ≥4 mRSS points within 6 months of Visit 1, OR
e) mRSS ≤25 at Visit 1, OR
f) anti-RNA polymerase III antibody positive and also a disease duration from first non-Raynaud’s symptom ≤2 years, OR
g) Anti-ScL70 antibody positive at Visit 1, OR
h) Muscle involvement at Visit 1 according to SCTC criteria, OR,
i) History or presence of digital ulcers at Visit 1, OR
j) DLCO % predicted corrected for haemoglobin (Hb) at Visit 1 <70%, OR
k) SSc-ILD (≥10% extent of fibrosis confirmed by central review of HRCT before randomisation)
6. Trial participants with lcSSc must have evidence of active disease during screening.
LcSSc patients must be anti-centromere antibody (ACA) negative. Active disease is defined as having at least one of the following:
a) Muscle involvement at Visit 1 according to SCTC criteria, OR,
b) History or presence of digital ulcers at Visit 1, OR c) DLCO % predicted corrected for Hb at Visit 1 <70%, OR d) SSc-ILD (≥10% extent of fibrosis confirmed by central review of HRCT before
randomisation), OR |
1. Major surgery (major according to the investigator’s assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement.
2. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
3. Trial participants who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial.
4. Patients exhibiting suicidality, in the clinical judgment of the investigator or according to the following criteria at Visit 1 and/or Visit 2:
• any suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour) in the past 2 years
• any suicidal ideation of type 4 or 5 on the C-SSRS (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent) in the past 3 months
5. Patients with clinically relevant severe depression (at the investigator’s discretion) or a HADS subscore >14 at Visit 1 and/or Visit 2.
6. Patients with active tuberculosis.
7. Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
8. Active unstable or uncontrolled vasculitis within 8 weeks prior to Visit 1 or during the screening period.
9. Patients treated with PDE4 inhibitors and non-selective PDE inhibitors within 30 days before Visit 1.
10. Patients who have received cyclophosphamide, rituximab, tocilizumab, abatacept, leflunomide, tacrolimus, tofacitinib, cyclosporine A, and potassium para-aminobenzoate within 24 weeks prior to Visit 2, and those not on stable treatment for peripheral arterial disease or Pulmonary Hypertension (PT) prior Visit 2.
11. Patients with end stage renal impairment (eGFR <15 mL/min/1.73 m2, based on CKD-Q formu |
Adult: 18 Year(s)-44 Year(s) |
18 Year(s) |
90 Year(s) |
Both |