Study Description
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. 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.
Interventions
rapcabtagene autoleucel
rituximab
Eligibility Criteria
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.
Novartis Investigative Site
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Darlinghurst,New South Wales,2010,Australia
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Camperdown,New South Wales,2050,Australia
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Vienna,1090,Austria
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Graz,8036,Austria
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São Paulo,São Paulo,01232-010,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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Paris,75014,France
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Lyon,69003,France
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Dijon,21000,France
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Montpellier,34295,France
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Rennes,35033,France
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Lille,59037,France
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Berlin,13353,Germany
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Göttingen,Lower Saxony,37075,Germany
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Jena,Thuringia,07740,Germany
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Mainz,55131,Germany
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Ulm,89081,Germany
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Halle,Saxony-Anhalt,06120,Germany
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Nuremberg,90419,Germany
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Leipzig,Saxony,04103,Germany
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Freiburg im Breisgau,Baden-Wurttemberg,79106,Germany
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Debrecen,Hajdu Bihar Megye,4032,Hungary
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Budapest,H-1083,Hungary
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Ramat Gan,5265601,Israel
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Tel Aviv,6423906,Israel
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Haifa,3109601,Israel
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Pavia,PV,27100,Italy
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Perugia,PG,06129,Italy
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Udine,UD,33100,Italy
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Brescia,BS,25123,Italy
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Pescara,PE,65124,Italy
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Bergamo,BG,24127,Italy
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Genova,GE,16132,Italy
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Roma,RM,00168,Italy
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Milan,MI,20122,Italy
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Milan,MI,20132,Italy
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Ancona,AN,60126,Italy
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Pisa,PI,56126,Italy
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Suita,Osaka,5650871,Japan
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Kyoto,6068507,Japan
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Kanazawa,Ishikawa-ken,920 8641,Japan
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Fukuoka,8128582,Japan
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Sapporo,Hokkaido,0608648,Japan
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Bunkyo-ku,Tokyo,113-8603,Japan
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Sendai,Miyagi,9808574,Japan
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Utrecht,3584 cx,Netherlands
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Singapore,169608,Singapore
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Seoul,06591,South Korea
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Málaga,29010,Spain
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Valencia,46026,Spain
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Santander,Cantabria,39008,Spain
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Pamplona,Navarre,31008,Spain
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Córdoba,14004,Spain
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Barcelona,08035,Spain
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Madrid,28009,Spain
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Madrid,28041,Spain
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Salamanca,37007,Spain
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Santiago Compostela,A Coruna,15706,Spain
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Barcelona,08041,Spain
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Geneva,1211,Switzerland
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Zurich,8091,Switzerland
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Lausanne,1011,Switzerland
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Taichung,407219,Taiwan
LDS Hospital
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Salt Lake City,Utah,84143,United States
Catherine Jennifer Bakewell
University of Minnesota
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Minneapolis,Minnesota,55455,United States
Hyun Kim
Amanda DeGrote
FL Medical Clinic Orlando Health
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Zephyrhills,Florida,33542,United States
Julio Gonzalez-Paoli
James Cancer Hospital
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Columbus,Ohio,43210,United States
Ali Ajam
University Of Iowa
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Iowa City,Iowa,52242,United States
Hanna Zembrzuska
Northwestern University
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Chicago,Illinois,60611,United States
George Georges
Matthew Selle
UCSF
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San Francisco,California,94115,United States
Emily Von Scheven
Michigan Med University of Michigan
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Ann Arbor,Michigan,48109 5271,United States
Monalisa Ghosh
Avera Cancer
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Sioux Falls,South Dakota,57105,United States
Xavier Andrade-Gonzalez
Oregon Health Sciences University
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Portland,Oregon,97239,United States
Atul Deodhar
Sutter Health Network
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San Pablo,California,94806,United States
Canary Jumawan
Neftali Nevarez
Boston Medical Center
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Boston,Massachusetts,02118,United States
Marcin Trojanowski
UCLA
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Los Angeles,California,90095,United States
Lauren Nam
Suzanne Kafaja
Worldwide Contacts
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