Placebo: Ianalumab matching placebo subcutaneous (s.c.) injection as defined in the protocol
Ianalumab: subcutaneous (s.c.) injection as defined in the protocol
Study summary
The purpose of this study is to evaluate efficacy, safety and tolerability of s.c. ianalumab administered in participants with diffuse cutaneous systemic sclerosis relative to placebo
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
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/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.
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. 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.
* 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.
Primary outcome measure(s)
3/5 rCRISS25 response — Week 52 To demonstrate the superiority of ianalumab, compared to placebo, in achieving 3/5 Revised Composite Response Index in Systemic Sclerosis 25 (rCRISS25) response at Week 52
Trial sites (128)
Facility
City
Region
Status
Arizona Arthritis and Rheumatology Research PLLC
Mesa
Arizona
Recruiting
UCLA
Los Angeles
California
Recruiting
Hoag Hospital
Newport Beach
California
Recruiting
Clinical Res Of W Florida
Clearwater
Florida
Recruiting
GNP Research
Cooper City
Florida
Recruiting
IRIS Research and Development
Plantation
Florida
Recruiting
Sarasota Arthritis Res Ctr
Sarasota
Florida
Active Not Recruiting
University of Chicago Hospitals
Chicago
Illinois
Recruiting
UMC New Orleans
New Orleans
Louisiana
Recruiting
Uni Of Michigan Health System
Ann Arbor
Michigan
Recruiting
Wayne State University
Detroit
Michigan
Recruiting
Clinical Research Inst of MI
Saint Clair Shores
Michigan
Recruiting
Hospital for Special Surgery
New York
New York
Recruiting
West Tennessee Research Institute
Jackson
Tennessee
Recruiting
Arthritis and Rheumatology Ins
Allen
Texas
Recruiting
Novel Research LLC
Bellaire
Texas
Recruiting
Prolato Clinical Research Center
Houston
Texas
Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Active Not Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Recruiting
Novartis Investigative Site
Caba
Argentina
Active Not Recruiting
Novartis Investigative Site
Caba
Argentina
Recruiting
Novartis Investigative Site
San Miguel de Tucumán
Argentina
Recruiting
Novartis Investigative Site
Graz
Austria
Recruiting
Novartis Investigative Site
Leuven
Belgium
Recruiting
Novartis Investigative Site
Salvador
Estado de Bahia
Recruiting
Novartis Investigative Site
Curitiba
Paraná
Recruiting
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
Recruiting
Novartis Investigative Site
Sao Jose Rio Preto
São Paulo
Recruiting
Novartis Investigative Site
São Paulo
São Paulo
Recruiting
Novartis Investigative Site
São Paulo
São Paulo
Recruiting
Novartis Investigative Site
Nanning
Guangxi
Recruiting
Novartis Investigative Site
Zhengzhou
Henan
Recruiting
Novartis Investigative Site
Changchun
Jilin
Recruiting
Novartis Investigative Site
Chengdu
Sichuan
Recruiting
Novartis Investigative Site
Ningbo
Zhejiang
Recruiting
Novartis Investigative Site
Beijing
China
Recruiting
Novartis Investigative Site
Beijing
China
Recruiting
Novartis Investigative Site
Tianjin
China
Recruiting
Novartis Investigative Site
Medellín
Antioquia
Active Not Recruiting
Novartis Investigative Site
Bogota
Cundinamarca
Active Not Recruiting
+ 88 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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