A Clinical Study to Evaluate Ianalumab in Participants With Diffuse Cutaneous Systemic Sclerosis

Korábbi kezelés

• Positive anti-centromere antibody (ACA+) without positive ATA or anti-RNAP3 autoantibody result at the screening visit
• Previous improvement (decrease) in mRSS > 10 units
• 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.
• 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. Patients with SSc-ILD requiring antifibrotics for management of ILD during the study, as per investigator judgement, should be excluded.
• Previous treatment with chlorambucil, bone marrow transplantation or total lymphoid irradiation.

Más betegség

• 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.
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 6 months after stopping study treatment.
  • Other protocol-defined inclusion/exclusion criteria may apply.

Laborértékek

• 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
• 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).

• 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/L)
  • Presence of SSc-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.