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
2 other identifiers
interventional
96
17 countries
78
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2024
Longer than P75 for phase_2
78 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2024
CompletedFirst Posted
Study publicly available on registry
October 24, 2024
CompletedStudy Start
First participant enrolled
October 29, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 30, 2032
February 20, 2026
February 1, 2026
4.1 years
October 22, 2024
February 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Achievement of a treatment response as per the Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) definition at Week 52.
To demonstrate the superiority of rapcabtagene autoleucel as a single infusion compared to rituximab, with respect to the proportion of participants achieving a Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) response at Week 52. This response is assessed across 5 assessment domains: (1) modified Rodnan Skin Score (mRSS), (2) Health Assessment Questionnaire Disability Index (HAQ-DI), (3) patient global assessment (PGA), (4) physician global assessment (PhGA) and (5) percent-predicted forced vital capacity (FVC%).
Week 52
Secondary Outcomes (4)
Change from baseline in Forced Vital Capacity (FVC)% predicted at Week 52
Baseline, Week 52
Change from baseline in modified Rodnan Skin Score (mRSS) at Week 52.
Baseline, Week 52
Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52.
Baseline, Week 52
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Up to end of study, assessed up to approximately 5 years
Study Arms (2)
rapcabtagene autoleucel arm
EXPERIMENTALrapcabtagene autoleucel
rituximab arm
ACTIVE COMPARATORrituximab
Interventions
single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (80)
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
Camperdown, New South Wales, 2050, Australia
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Darlinghurst, New South Wales, 2010, Australia
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Graz, 8036, Austria
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Vienna, 1090, 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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Bordeaux, 33076, France
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Dijon, 21000, France
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Lille, 59037, France
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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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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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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, 60126, 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, 0608648, Japan
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Kanazawa, Ishikawa-ken, 920 8641, Japan
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Sendai, Miyagi, 9808574, Japan
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Suita, Osaka, 5650871, Japan
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Bunkyo-ku, Tokyo, 113-8603, Japan
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Fukuoka, 8128582, 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, 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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- The study investigator and the participant will be unblinded to the study treatment. A blinded assessor will perform the efficacy assessments to minimize bias in data collection.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2024
First Posted
October 24, 2024
Study Start
October 29, 2024
Primary Completion (Estimated)
November 30, 2028
Study Completion (Estimated)
August 30, 2032
Last Updated
February 20, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.