Clinical Trial Finder

Key

Inclusion Criteria:

• - Male and female participants >= 18 and =< 70 years (at the time of the screening visit).

• - Diagnosis of systemic sclerosis, as defined by the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria for SSc (van den Hoogen et al 2013) and meet the dcSSc subset classification according to LeRoy (LeRoy 1988) - Disease duration of =< 60 months (defined as time from the first non-Raynaud phenomenon manifestation, e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea) - mRSS units of >= 15 and =< 45 at the time of the screening visit.

• - Active disease that meets at least one of the following criteria at screening: - Disease duration of =< 18 months defined as time from the first non-Raynaud phenomenon manifestation.

• - Increase in mRSS of >= 3 units compared with the most recent assessment performed within the previous 6 months.

• - Involvement of one new body area and an increase in mRSS of >= 2 units compared with the most recent assessment performed within the previous 6 months.

• - Involvement of two new body areas within the previous 6 months.

• - Elevated acute phase reactants (ESR) >= 30 mm/hr or high-sensitivity C-reactive protein (hsCRP) >= 6 mg/dL) - Presence of interstitial lung disease (ILD) and ATA autoantibody positivity.

• - Modified EUSTAR disease activity index (mDAI) > 2.5.

• - Participant must be positive for at least one of the following autoantibodies: - anti-topoisomerase I (ATA) (also known as anti-SCL-70) - anti-RNA polymerase III (anti-RNAP3) - anti-nuclear antibody (ANA) (≥ 1:80) Participants who are positive only for ANA (while being negative for both ATA /anti-RNAP3) will be limited to 30% of the overall randomized study population.

Key

Exclusion Criteria:

• - Rheumatic disease other than dcSSc, including limited cutaneous disease (lcSSc) or sine scleroderma at the screening visit.

Secondary Sjogren's disease and scleroderma myopathy are not exclusionary.

• - Positive anti-centromere antibody (ACA+) without positive ATA or anti-RNAP3 autoantibody result at the screening visit.

• - Previous improvement (decrease) in mRSS > 10 units.

• - Pulmonary disease with FVC ≤ 50% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO, corrected for hemoglobin) ≤ 40% of predicted at the screening visit.

• - WHO Functional Class 3 or higher assessment for pulmonary arterial hypertension (PAH, as defined on right heart catheterization), receiving IV therapy for PAH or evidence of other moderately severe pulmonary disease.

• - Participants treated with cyclophosphamide within 12 weeks prior to Baseline.

• - Prior use of a B-cell depleting therapy other than ianalumab (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) administered within 36 weeks prior to randomization, or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower) - Treatment with biologic agents, such as intravenous immunoglobulin or monoclonal antibodies, including marketed drugs, within 12 weeks or 5 half-lives (whichever is longer) prior to baseline visit, unless explicitly allowed in inclusion criteria.

• - Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit.

• - Use of anti-fibrotic agents including colchicine, D-penicillamine, pirfenidone, or tyrosine kinase inhibitors (e.g., nintedanib, nilotinib, imatinib, dasatinib) in the 4 weeks prior to baseline visit.

• - Previous treatment with chlorambucil, bone marrow transplantation or total lymphoid irradiation.

Other protocol-defined inclusion/exclusion criteria may apply.

The study consists of the following periods:

• - Screening Period, with a duration of up to 6 weeks; - Treatment Period 1, with a duration of 52 weeks; - Treatment Period 2 (Open-label treatment), with a duration of 52 weeks; - Post-treatment Follow-up Period, with a duration of at least 20 weeks post last dose and up to 2 years.

Arms

Experimental: VAY736 (Ianalumab)

Treatment Period 1: Ianalumab subcutaneous (s.c.) injection as defined in the protocol Treatment Period 2: Open-label (OL) Ianalumab subcutaneous (s.c.) injection as defined in the protocol

Placebo Comparator: Placebo

Treatment Period 1: Placebo to Ianalumab subcutaneous (s.c.) injection as defined in the protocol Treatment Period 2: Open-label (OL) Ianalumab subcutaneous (s.c.) injection as defined in the protocol

Interventions

Drug: - Placebo

Ianalumab matching placebo subcutaneous (s.c.) injection as defined in the protocol

Drug: - Ianalumab

subcutaneous (s.c.) injection as defined in the protocol