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NCT06655896PHASE2Recruiting

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis

Novartis Pharmaceuticals

Start Date

10/29/2024

Completion Date

8/30/2032

Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following lymphodepletion) in participants with severe refractory diffuse cutaneous systemic sclerosis relative to rituximab.

Detailed Description

This is a phase 2, multi-part, five-year, randomized, open-label, assessor-blinded, multicenter study to evaluate the efficacy and safety of rapcabtagene autoleucel versus rituximab in participants with severe refractory diffuse cutaneous systemic sclerosis (dcSSc). This study comprises two cohorts: * A Lead-in Cohort enrolling participants to receive rapcabtagene autoleucel. * A Randomized Cohort enrolling participants to receive rapcabtagene autoleucel or rituximab. Participants in the rituximab arm whose disease is not fully controlled may receive rapcabtagene autoleucel treatment once the participant is confirmed to be eligible per protocol. After end of study, participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up (LTFU) period after rapcabtagene autoleucel infusion. This LTFU will be described in a separate study protocol.

Eligibility Criteria

Age Range: 18 years to 70 years

Inclusion Criteria: 1. Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy. 2. Disease onset from the first non-Raynaud symptoms attributable to SSc (e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea) within 7 years prior to the Screening visit. 3. Severe, progressive systemic sclerosis disease defined by at least one of the following: * Progressive systemic sclerosis-associated interstitial lung disease * Severe, progressive systemic sclerosis skin disease * Clinically significant systemic sclerosis-associated cardiac involvement at Screening 4. All recommended vaccinations received according to institutional, local or global guidelines for immuno-compromised patients. Exclusion Criteria: 1. Any condition during Screening that could prevent a complete washout of medications as required per protocol or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study, as judged by the Investigator. 2. Participants with history of hypersensitivity to excipients in rapcabtagene autoleucel or to rituximab. 3. Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator. 4. Any medical conditions that are not related to SSc that, in the opinion of the Investigator, would jeopardize the ability of the participant to tolerate lymphodepletion and anti-CD19 CAR-T cell therapy. 5. Rheumatic disease other than dcSSc, (except secondary Sjogren's syndrome or scleroderma myopathy),including limited cutaneous systemic sclerosis (lcSSc) or sine scleroderma at Screening. 6. Participants with pre-existing pulmonary hypertension. 7. Significant renal pathology at Screening. 8. Participants with uncontrolled stage II hypertension at Screening. 9. Vaccination with live attenuated vaccines within 6 weeks prior to randomization. Other protocol-defined inclusion/exclusion criteria may apply.

Interventions

BIOLOGICAL

rapcabtagene autoleucel

BIOLOGICAL

rituximab

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Conditions

Scleroderma, Diffuse

Locations

UCLA

Los Angeles, California 90095

United States

UCSF

San Francisco, California 94115

United States

UCSF

San Francisco, California 94115

United States

Sutter Health Network

San Pablo, California 94806

United States

FL Medical Clinic Orlando Health

Zephyrhills, Florida 33542

United States

Northwestern University

Chicago, Illinois 60611

United States

University Of Iowa

Iowa City, Iowa 52242

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Michigan Med University of Michigan

Ann Arbor, Michigan 48109 5271

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

James Cancer Hospital

Columbus, Ohio 43210

United States

Oregon Health Sciences University

Portland, Oregon 97239

United States

Avera Cancer

Sioux Falls, South Dakota 57105

United States

LDS Hospital

Salt Lake City, Utah 84143

United States

Novartis Investigative Site

CABA, C1181ACH

Argentina

Novartis Investigative Site

Córdoba, X5016KEH

Argentina

Novartis Investigative Site

Camperdown, New South Wales 2050

Australia

Novartis Investigative Site

Darlinghurst, New South Wales 2010

Australia

Novartis Investigative Site

Graz, 8036

Austria

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Vienna, 1090

Austria

Novartis Investigative Site

Ghent, 9000

Belgium

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Salvador, Estado de Bahia 41253-190

Brazil

Novartis Investigative Site

Curitiba, Paraná 80030-110

Brazil

Novartis Investigative Site

Barretos, São Paulo 14784 400

Brazil

Novartis Investigative Site

São Paulo, São Paulo 01232-010

Brazil

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São Paulo, São Paulo 01308-050

Brazil

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Olomouc, 779 00

Czechia

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Prague, 128 00

Czechia

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Aarhus N, 8200

Denmark

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Bordeaux, 33076

France

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Dijon, 21000

France

Novartis Investigative Site

Lille, 59037

France

Novartis Investigative Site

Lyon, 69003

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, 67091

France

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Freiburg im Breisgau, Baden-Wurttemberg 79106

Germany

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Göttingen, Lower Saxony 37075

Germany

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Leipzig, Saxony 04103

Germany

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Halle, Saxony-Anhalt 06120

Germany

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Jena, Thuringia 07740

Germany

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Berlin, 13353

Germany

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Lübeck, 23538

Germany

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Mainz, 55131

Germany

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Nuremberg, 90419

Germany

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Ulm, 89081

Germany

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Debrecen, Hajdu Bihar Megye 4032

Hungary

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Budapest, H-1083

Hungary

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Haifa, 3109601

Israel

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Ramat Gan, 5265601

Israel

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Tel Aviv, 6423906

Israel

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Ancona, AN 60020

Italy

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Bergamo, BG 24127

Italy

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Brescia, BS 25123

Italy

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Genova, GE 16132

Italy

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Milan, MI 20122

Italy

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Milan, MI 20132

Italy

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Pescara, PE 65124

Italy

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Perugia, PG 06129

Italy

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Pisa, PI 56126

Italy

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Pavia, PV 27100

Italy

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Roma, RM 00168

Italy

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Udine, UD 33100

Italy

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Sapporo, Hokkaido 060-8648

Japan

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Sendai, Miyagi 9808574

Japan

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Suita, Osaka 565-0871

Japan

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Bunkyo-ku, Tokyo 113-8603

Japan

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Fukuoka, 8128582

Japan

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Ishikawa, 9208641

Japan

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Kyoto, 6068507

Japan

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Utrecht, 3584 CX

Netherlands

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Singapore, 169608

Singapore

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Seoul, 04763

South Korea

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Seoul, 06351

South Korea

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Seoul, 06591

South Korea

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Santiago Compostela, A Coruna 15706

Spain

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Santander, Cantabria 39008

Spain

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Pamplona, Navarre 31008

Spain

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Barcelona, 08035

Spain

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Barcelona, 08041

Spain

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Córdoba, 14004

Spain

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Madrid, 28009

Spain

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Madrid, 28041

Spain

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Málaga, 29010

Spain

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Salamanca, 37007

Spain

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Valencia, 46026

Spain

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Geneva, 1211

Switzerland

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Lausanne, 1011

Switzerland

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Zurich, 8091

Switzerland

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Taichung, 407219

Taiwan

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Sheffield, South Yorkshire S10 2JF

United Kingdom