RecruitingPhase 2NCT06655896

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

A Phase II, Multi-part, Randomized, Open-label, Assessor-blinded, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Rapcabtagene Autoleucel Versus Rituximab Treatment in Participants With Severe Refractory Diffuse Cutaneous Systemic Sclerosis


Sponsor

Novartis Pharmaceuticals

Enrollment

96 participants

Start Date

Oct 29, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria7

  • 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.
  • 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.
  • 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
  • All recommended vaccinations received according to institutional, local or global guidelines for immuno-compromised patients.

Exclusion Criteria9

  • 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.
  • Participants with history of hypersensitivity to excipients in rapcabtagene autoleucel or to rituximab.
  • Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator.
  • 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.
  • Rheumatic disease other than dcSSc, (except secondary Sjogren's syndrome or scleroderma myopathy),including limited cutaneous systemic sclerosis (lcSSc) or sine scleroderma at Screening.
  • Participants with pre-existing pulmonary hypertension.
  • Significant renal pathology at Screening.
  • Participants with uncontrolled stage II hypertension at Screening.
  • Vaccination with live attenuated vaccines within 6 weeks prior to randomization.

Interventions

BIOLOGICALrapcabtagene autoleucel

single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.

BIOLOGICALrituximab

rituximab intravenous infusion (i.v.) as per protocol


Locations(80)

UCLA

Los Angeles, California, United States

UCSF

San Francisco, California, United States

UCSF

San Francisco, California, United States

Sutter Health Network

San Pablo, California, United States

FL Medical Clinic Orlando Health

Zephyrhills, Florida, United States

Northwestern University

Chicago, Illinois, United States

University Of Iowa

Iowa City, Iowa, United States

Boston Medical Center

Boston, Massachusetts, United States

Michigan Med University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

James Cancer Hospital

Columbus, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

Avera Cancer

Sioux Falls, South Dakota, United States

LDS Hospital

Salt Lake City, Utah, United States

Novartis Investigative Site

Camperdown, New South Wales, Australia

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

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Graz, Austria

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Vienna, Austria

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São Paulo, São Paulo, Brazil

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Olomouc, Czechia

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Prague, Czechia

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Aarhus N, Denmark

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Bordeaux, France

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Dijon, France

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Lille, France

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Lyon, France

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Montpellier, France

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Paris, France

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Rennes, France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Göttingen, Lower Saxony, Germany

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Leipzig, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Jena, Thuringia, Germany

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Berlin, Germany

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Mainz, Germany

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Nuremberg, Germany

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Ulm, Germany

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Debrecen, Hajdu Bihar Megye, Hungary

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Budapest, Hungary

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Haifa, Israel

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Ramat Gan, Israel

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Tel Aviv, Israel

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Ancona, AN, Italy

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Bergamo, BG, Italy

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Brescia, BS, Italy

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Genova, GE, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Pescara, PE, Italy

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Perugia, PG, Italy

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Pisa, PI, Italy

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Pavia, PV, Italy

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Roma, RM, Italy

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Udine, UD, Italy

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Sapporo, Hokkaido, Japan

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Kanazawa, Ishikawa-ken, Japan

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Sendai, Miyagi, Japan

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Suita, Osaka, Japan

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Bunkyo-ku, Tokyo, Japan

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Fukuoka, Japan

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Kyoto, Japan

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Utrecht, Netherlands

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Singapore, Singapore

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Seoul, South Korea

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Santiago Compostela, A Coruna, Spain

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Santander, Cantabria, Spain

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Pamplona, Navarre, Spain

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Barcelona, Spain

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Barcelona, Spain

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Córdoba, Spain

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Madrid, Spain

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Madrid, Spain

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Málaga, Spain

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Salamanca, Spain

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Valencia, Spain

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Geneva, Switzerland

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Lausanne, Switzerland

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Zurich, Switzerland

Novartis Investigative Site

Taichung, Taiwan

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NCT06655896