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

Official title

A Randomized, Double-blind, Parallel Group, Placebo-controlled Multicenter Study to Evaluate Efficacy, Safety and Tolerability of Ianalumab in Participants With Diffuse Cutaneous Systemic Sclerosis

Overview

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

Detailed description

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.

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

Primary outcome measures

• 3/5 rCRISS25 response [Time frame: Week 52]

Secondary outcome measures (6)

• Change from baseline in FVC% predicted at Week 52 [Time frame: Week 52]
• Change from baseline in mRSS at Week 52 [Time frame: Week 52]
• Change from baseline in HAQ-DI at Week 52 [Time frame: Week 52]
• Ianalumab concentrations in serum during treatment and Follow-up Period [Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, Week 64, Week 76, Week 88, Week 104, Week 108, Week 112, Week 116, Week 120, Week 124 and Week 208]
• Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time [Time frame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, Week 64, Week 76, Week 88, Week 104, Week 124, Week 208]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to Week 208]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Japan · 18 centers

• Novartis Investigative Site — Nagoya
• Novartis Investigative Site — Toyoake
• Novartis Investigative Site — Kitakyushu
• Novartis Investigative Site — Maebashi
• Novartis Investigative Site — Sapporo
• … and 13 more centers

United States · 17 centers

• Arizona Arthritis and Rheumatology Research PLLC — Mesa
• UCLA — Los Angeles
• Hoag Hospital — Newport Beach
• Clinical Res Of W Florida — Clearwater
• GNP Research — Cooper City
• IRIS Research and Development — Plantation
• Sarasota Arthritis Res Ctr — Sarasota
• University of Chicago Hospitals — Chicago
• … and 9 more centers

China · 8 centers

• Novartis Investigative Site — Nanning
• Novartis Investigative Site — Zhengzhou
• Novartis Investigative Site — Changchun
• Novartis Investigative Site — Chengdu
• Novartis Investigative Site — Ningbo
• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Tianjin

France · 8 centers

• Novartis Investigative Site — Dijon
• Novartis Investigative Site — Le Mans
• Novartis Investigative Site — Lille
• Novartis Investigative Site — Montpellier
• Novartis Investigative Site — Paris
• Novartis Investigative Site — Rennes
• Novartis Investigative Site — Strasbourg
• Novartis Investigative Site — Toulouse

Italy · 8 centers

• Novartis Investigative Site — Ancona
• Novartis Investigative Site — Milan
• Novartis Investigative Site — Rozzano
• Novartis Investigative Site — Modena
• Novartis Investigative Site — Palermo
• Novartis Investigative Site — Pavia
• Novartis Investigative Site — Roma
• Novartis Investigative Site — Verona

Brazil · 6 centers

• Novartis Investigative Site — Salvador
• Novartis Investigative Site — Curitiba
• Novartis Investigative Site — Porto Alegre
• Novartis Investigative Site — Sao Jose Rio Preto
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo

Colombia · 6 centers

• Novartis Investigative Site — Medellín
• Novartis Investigative Site — Bogota
• Novartis Investigative Site — Bogota
• Novartis Investigative Site — Cali
• Novartis Investigative Site — Bogotá
• Novartis Investigative Site — Medellín

India · 6 centers

• Novartis Investigative Site — Kochi
• Novartis Investigative Site — Mumbai
• Novartis Investigative Site — Mumbai
• Novartis Investigative Site — New Delhi
• Novartis Investigative Site — New Delhi
• Novartis Investigative Site — Jaipur

Argentina · 5 centers

• Novartis Investigative Site — CABA
• Novartis Investigative Site — CABA
• Novartis Investigative Site — Caba
• Novartis Investigative Site — Caba
• Novartis Investigative Site — San Miguel de Tucumán

Mexico · 5 centers

Center list to be confirmed — check the primary protocol.

Spain · 5 centers

Center list to be confirmed — check the primary protocol.

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 4 centers

Center list to be confirmed — check the primary protocol.

Germany · 3 centers

• Novartis Investigative Site — Würzburg
• Novartis Investigative Site — Jena
• Novartis Investigative Site — Berlin

Greece · 3 centers

• Novartis Investigative Site — Alexandroupoli
• Novartis Investigative Site — Athens
• Novartis Investigative Site — Athens

Hungary · 3 centers

• Novartis Investigative Site — Pécs
• Novartis Investigative Site — Debrecen
• Novartis Investigative Site — Budapest

Portugal · 3 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 3 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 3 centers

Center list to be confirmed — check the primary protocol.

Malaysia · 2 centers

Center list to be confirmed — check the primary protocol.

Poland · 2 centers

Center list to be confirmed — check the primary protocol.

Thailand · 2 centers

Center list to be confirmed — check the primary protocol.

Vietnam · 2 centers

Center list to be confirmed — check the primary protocol.

Austria · 1 center

• Novartis Investigative Site — Graz

Belgium · 1 center

• Novartis Investigative Site — Leuven

Publications

• Lescoat A, Lecureur V, Gudjonsson JE, Khanna D. Systemic sclerosis: pathogenic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Nov 11;47(1):39. doi: 10.1007/s00281-025-01065-6. PMID 41217519

Identifiers

NCT: NCT06470048 · CVAY736S12201 · 2024-511933-36-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗