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
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
Recruiting
Darlinghurst,New South Wales,2010,Australia
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Bordeaux Cedex,33076,France
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Dijon,21034,France
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Rennes,35043,France
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Montpellier,34295,France
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Jena,07740,Germany
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Leipzig,Sachsen,04103,Germany
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Berlin,13353,Germany
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Haifa,3109601,Israel
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Tel Aviv,6423906,Israel
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Ramat Gan,5265601,Israel
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Brescia,BS,25123,Italy
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Pisa,PI,56124,Italy
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Pavia,PV,27100,Italy
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Ancona,AN,60126,Italy
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Roma,RM,00168,Italy
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Genova,GE,16132,Italy
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Bergamo,BG,24127,Italy
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Kanazawa,Ishikawa,920 8641,Japan
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Sendai city,Miyagi,980 8574,Japan
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Suita,Osaka,565 0871,Japan
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Kyoto,606 8507,Japan
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Sapporo city,Hokkaido,060 8648,Japan
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Utrecht,3584,Netherlands
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Singapore,169608,Singapore
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Barcelona,Catalunya,08035,Spain
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Pamplona,Navarra,31008,Spain
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Madrid,28041,Spain
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Barcelona,08041,Spain
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Cordoba,Andalucia,14004,Spain
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Lausanne,1011,Switzerland
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Taichung,407219,Taiwan
Avera Cancer
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Sioux Falls,South Dakota,57105,United States
Xavier Andrade-Gonzalez
UCSF
Recruiting
San Francisco,California,94115,United States
Emily Von Scheven
Northwestern University
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Chicago,Illinois,60611,United States
George Georges
Kathleen Aren
University Of Iowa
Recruiting
Iowa City,Iowa,52242,United States
Hanna Zembrzuska
Michigan Med University of Michigan
Recruiting
Ann Arbor,Michigan,48109 5271,United States
Monalisa Ghosh
Worldwide Contacts
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