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NCT06470048PHASE2Recruiting

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

Novartis Pharmaceuticals

Start Date

10/9/2024

Completion Date

7/31/2034

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

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.

Eligibility Criteria

Age Range: 18 years to 70 years

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.

Interventions

DRUG

Placebo

DRUG

Ianalumab

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Conditions

Diffuse Cutaneous Systemic Sclerosis

Locations

Arizona Arthritis and Rheumatology Research PLLC

Mesa, Arizona 85202

United States

UCLA

Los Angeles, California 90095

United States

Hoag Hospital

Newport Beach, California 92663

United States

Clinical Res Of W Florida

Clearwater, Florida 33765

United States

GNP Research

Cooper City, Florida 33024

United States

IRIS Research and Development

Plantation, Florida 33324

United States

Sarasota Arthritis Res Ctr

Sarasota, Florida 34239

United States

University of Chicago Hospitals

Chicago, Illinois 60637

United States

UMC New Orleans

New Orleans, Louisiana 70112

United States

Uni Of Michigan Health System

Ann Arbor, Michigan 48109

United States

Wayne State University

Detroit, Michigan 48201

United States

Clinical Research Inst of MI

Saint Clair Shores, Michigan 48081

United States

Hospital for Special Surgery

New York, New York 10021

United States

West Tennessee Research Institute

Jackson, Tennessee 38305

United States

Arthritis and Rheumatology Ins

Allen, Texas 75035

United States

Novel Research LLC

Bellaire, Texas 77401

United States

Prolato Clinical Research Center

Houston, Texas 77054

United States

Novartis Investigative Site

CABA, Buenos Aires C1221ADC

Argentina

Novartis Investigative Site

CABA, Buenos Aires C1280AEB

Argentina

Novartis Investigative Site

Caba, C1015ABO

Argentina

Novartis Investigative Site

Caba, C1427CCL

Argentina

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San Miguel de Tucumán, T4000AXL

Argentina

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Graz, 8036

Austria

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Leuven, 3000

Belgium

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Salvador, Estado de Bahia 40150 150

Brazil

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Curitiba, Paraná 80030-110

Brazil

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul 90035-074

Brazil

Novartis Investigative Site

Sao Jose Rio Preto, São Paulo 15090 000

Brazil

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São Paulo, São Paulo 04038-002

Brazil

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São Paulo, São Paulo 05403-000

Brazil

Novartis Investigative Site

Nanning, Guangxi 530021

China

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Zhengzhou, Henan 450003

China

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Changchun, Jilin 130021

China

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Chengdu, Sichuan 610041

China

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Ningbo, Zhejiang 315016

China

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Beijing, 100191

China

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Beijing, 100730

China

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Tianjin, 300052

China

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Medellín, Antioquia 050001

Colombia

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Bogota, Cundinamarca 110111

Colombia

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Bogota, Cundinamarca 110221

Colombia

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Cali, Valle del Cauca Department 760012

Colombia

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Bogotá, 110231

Colombia

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Medellín, 050034

Colombia

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Dijon, 21000

France

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Le Mans, 72000

France

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Lille, 59037

France

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Montpellier, 34295

France

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Paris, 75014

France

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Rennes, 35033

France

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Strasbourg, 67000

France

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Toulouse, 31054

France

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Würzburg, Bavaria 97080

Germany

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Jena, Thuringia 07740

Germany

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Berlin, 13353

Germany

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Alexandroupoli, 681 00

Greece

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Athens, 115 21

Greece

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Athens, 115 27

Greece

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Pécs, Baranya 7623

Hungary

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Debrecen, Hajdu Bihar Megye 4032

Hungary

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Budapest, H-1083

Hungary

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Kochi, Kerala 682018

India

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Mumbai, Maharashtra 400013

India

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Mumbai, Maharashtra 400078

India

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New Delhi, National Capital Territory of Delhi 110060

India

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New Delhi, New Delhi 110029

India

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Jaipur, Rajasthan 302004

India

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Ancona, AN 60020

Italy

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Milan, MI 20100

Italy

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Rozzano, MI 20089

Italy

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Modena, MO 41124

Italy

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Palermo, PA 90127

Italy

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Pavia, PV 27100

Italy

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Roma, RM 00168

Italy

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Verona, VR 37134

Italy

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Nagoya, Aichi-ken 4578510

Japan

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Toyoake, Aichi-ken 4701192

Japan

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Kitakyushu, Fukuoka 8078556

Japan

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Maebashi, Gunma 3718511

Japan

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Sapporo, Hokkaido 060-8648

Japan

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Sapporo, Hokkaido 0608543

Japan

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Yokohama, Kanagawa 236-0004

Japan

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Suita, Osaka 565-0871

Japan

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Iruma-gun, Saitama 3500495

Japan

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Bunkyo-ku, Tokyo 113-8603

Japan

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Chuo Ku, Tokyo 104-8560

Japan

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Shinjuku Ku, Tokyo 1628666

Japan

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Shinjuku-ku, Tokyo 1608582

Japan

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Toyama, Toyama 9300194

Japan

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Fukuoka, 8128582

Japan

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Hiroshima, 7348551

Japan

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Ishikawa, 9208641

Japan

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Kyoto, 6068507

Japan

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Cheras, Kuala Lumpur 56000

Malaysia

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Kuala Lumpur, 59100

Malaysia

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Chihuahua City, Chihuahua 31000

Mexico

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Guadalajara, Jalisco 44650

Mexico

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Mexico City, Mexico City 06700

Mexico

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Mexico City, Mexico City 11850

Mexico

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Monterrey, Nuevo León 64460

Mexico

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Bydgoszcz, 85-168

Poland

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Warsaw, 00-874

Poland

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Coimbra, 3004-561

Portugal

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Lisbon, 1649-035

Portugal

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Vila Nova de Gaia, 4434 502

Portugal

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Seoul, Seoul 03080

South Korea

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Busan, 49241

South Korea

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Seoul, 04763

South Korea

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Seoul, 06273

South Korea

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Málaga, Andalusia 29009

Spain

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Valencia, Valencia 46017

Spain

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Barcelona, 08041

Spain

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Madrid, 28009

Spain

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Salamanca, 37007

Spain

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Changhua, 50006

Taiwan

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Kaohsiung City, 833

Taiwan

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Taichung, 40447

Taiwan

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Taoyuan, 33305

Taiwan

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Khon Kaen, THA 40002

Thailand

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Bangkok, 10400

Thailand

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Istanbul, Fatih 34093

Turkey (Türkiye)

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Ankara, Sihhiye-Altindag 06230

Turkey (Türkiye)

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Ankara, Yenimahalle 06500

Turkey (Türkiye)

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Basingstoke, Hampshire RG24 9NA

United Kingdom

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Bristol, BS10 5NB

United Kingdom

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London, NW3 2QG

United Kingdom

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Ho Chi Minh City, VNM 700000

Vietnam

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Ho Chi Minh City, 700000

Vietnam