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

June 2, 2026 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

96

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Novartis Investigative Site
      • Darlinghurst, New South Wales, Australia, 2010
        • Recruiting
        • Novartis Investigative Site
  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • Novartis Investigative Site
      • Vienna, Austria, 1090
        • Recruiting
        • Novartis Investigative Site
  • Belgium
      • Ghent, Belgium, 9000
        • Recruiting
        • Novartis Investigative Site
  • Brazil
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41253-190
        • Recruiting
        • Novartis Investigative Site
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784 400
        • Recruiting
        • Novartis Investigative Site
      • São Paulo, São Paulo, Brazil, 01308-050
        • Recruiting
        • Novartis Investigative Site
      • São Paulo, São Paulo, Brazil, 01232-010
        • Recruiting
        • Novartis Investigative Site
  • Czechia
      • Olomouc, Czechia, 779 00
        • Recruiting
        • Novartis Investigative Site
      • Prague, Czechia, 128 00
        • Recruiting
        • Novartis Investigative Site
  • Denmark
      • Aarhus N, Denmark, 8200
        • Recruiting
        • Novartis Investigative Site
  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Novartis Investigative Site
      • Dijon, France, 21000
        • Recruiting
        • Novartis Investigative Site
      • Lille, France, 59037
        • Recruiting
        • Novartis Investigative Site
      • Lyon, France, 69003
        • Recruiting
        • Novartis Investigative Site
      • Montpellier, France, 34295
        • Recruiting
        • Novartis Investigative Site
      • Paris, France, 75014
        • Recruiting
        • Novartis Investigative Site
      • Rennes, France, 35033
        • Recruiting
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Novartis Investigative Site
      • Lübeck, Germany, 23538
        • Recruiting
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Recruiting
        • Novartis Investigative Site
      • Nuremberg, Germany, 90419
        • Recruiting
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Recruiting
        • Novartis Investigative Site
    • Baden-Wurttemberg
      • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
        • Recruiting
        • Novartis Investigative Site
    • Lower Saxony
      • Göttingen, Lower Saxony, Germany, 37075
        • Recruiting
        • Novartis Investigative Site
    • Saxony
      • Leipzig, Saxony, Germany, 04103
        • Recruiting
        • Novartis Investigative Site
    • Saxony-Anhalt
      • Halle, Saxony-Anhalt, Germany, 06120
        • Recruiting
        • Novartis Investigative Site
    • Thuringia
      • Jena, Thuringia, Germany, 07740
        • Recruiting
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, H-1083
        • Recruiting
        • Novartis Investigative Site
    • Hajdu Bihar Megye
      • Debrecen, Hajdu Bihar Megye, Hungary, 4032
        • Recruiting
        • Novartis Investigative Site
  • Israel
      • Haifa, Israel, 3109601
        • Recruiting
        • Novartis Investigative Site
      • Ramat Gan, Israel, 5265601
        • Recruiting
        • Novartis Investigative Site
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Novartis Investigative Site
  • Italy
    • AN
      • Ancona, AN, Italy, 60126
        • Recruiting
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italy, 24127
        • Recruiting
        • Novartis Investigative Site
    • BS
      • Brescia, BS, Italy, 25123
        • Recruiting
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Recruiting
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italy, 20122
        • Recruiting
        • Novartis Investigative Site
      • Milan, MI, Italy, 20132
        • Recruiting
        • Novartis Investigative Site
    • PE
      • Pescara, PE, Italy, 65124
        • Recruiting
        • Novartis Investigative Site
    • PG
      • Perugia, PG, Italy, 06129
        • Recruiting
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Recruiting
        • Novartis Investigative Site
    • PV
      • Pavia, PV, Italy, 27100
        • Recruiting
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00168
        • Recruiting
        • Novartis Investigative Site
    • UD
      • Udine, UD, Italy, 33100
        • Recruiting
        • Novartis Investigative Site
  • Japan
      • Fukuoka, Japan, 8128582
        • Recruiting
        • Novartis Investigative Site
      • Ishikawa, Japan, 9208641
        • Recruiting
        • Novartis Investigative Site
      • Kyoto, Japan, 6068507
        • Recruiting
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Recruiting
        • Novartis Investigative Site
    • Miyagi
      • Sendai, Miyagi, Japan, 9808574
        • Recruiting
        • Novartis Investigative Site
    • Osaka
      • Suita, Osaka, Japan, 565-0871
        • Recruiting
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8603
        • Recruiting
        • Novartis Investigative Site
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169608
        • Recruiting
        • Novartis Investigative Site
  • South Korea
      • Seoul, South Korea, 06591
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 04763
        • Recruiting
        • Novartis Investigative Site
  • Spain
      • Barcelona, Spain, 08041
        • Recruiting
        • Novartis Investigative Site
      • Barcelona, Spain, 08035
        • Recruiting
        • Novartis Investigative Site
      • Córdoba, Spain, 14004
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28041
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28009
        • Recruiting
        • Novartis Investigative Site
      • Málaga, Spain, 29010
        • Recruiting
        • Novartis Investigative Site
      • Salamanca, Spain, 37007
        • Recruiting
        • Novartis Investigative Site
      • Valencia, Spain, 46026
        • Recruiting
        • Novartis Investigative Site
    • A Coruna
      • Santiago Compostela, A Coruna, Spain, 15706
        • Recruiting
        • Novartis Investigative Site
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Recruiting
        • Novartis Investigative Site
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Novartis Investigative Site
  • Switzerland
      • Geneva, Switzerland, 1211
        • Recruiting
        • Novartis Investigative Site
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Novartis Investigative Site
      • Zurich, Switzerland, 8091
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Taichung, Taiwan, 407219
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Recruiting
        • Novartis Investigative Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA
        • Principal Investigator:
          • Suzanne Kafaja
        • Contact:
      • San Francisco, California, United States, 94115
        • Recruiting
        • UCSF
        • Principal Investigator:
          • Emily Von Scheven
        • Contact:
      • San Pablo, California, United States, 94806
    • Florida
      • Zephyrhills, Florida, United States, 33542
        • Recruiting
        • FL Medical Clinic Orlando Health
        • Contact:
        • Principal Investigator:
          • Julio Gonzalez-Paoli
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Principal Investigator:
          • George Georges
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Hanna Zembrzuska
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
        • Principal Investigator:
          • Marcin Trojanowski
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109 5271
        • Recruiting
        • Michigan Med University of Michigan
        • Principal Investigator:
          • Monalisa Ghosh
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Principal Investigator:
          • Hyun Kim
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • James Cancer Hospital
        • Principal Investigator:
          • Ali Ajam
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health Sciences University
        • Principal Investigator:
          • Atul Deodhar
        • Contact:
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Recruiting
        • Avera Cancer
        • Principal Investigator:
          • Xavier Andrade-Gonzalez
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • Recruiting
        • LDS Hospital
        • Principal Investigator:
          • Catherine Jennifer Bakewell
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rapcabtagene autoleucel arm
rapcabtagene autoleucel
Biological: rapcabtagene autoleucel
single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.
Active Comparator: rituximab arm
rituximab
Biological: rituximab
rituximab intravenous infusion (i.v.) as per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Achievement of a treatment response as per the Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) definition at Week 52.
Time Frame: 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Forced Vital Capacity (FVC)% predicted at Week 52
Time Frame: Baseline, Week 52
Change from baseline in FVC % predicted
Baseline, Week 52
Change from baseline in modified Rodnan Skin Score (mRSS) at Week 52.
Time Frame: Baseline, Week 52
The modified Rodnan Skin Score (mRSS) is a clinical tool used to assess skin thickness in patients with systemic sclerosis (scleroderma). It involves palpating the skin and rating its thickness on a scale from 0 to 3 across 17 different body sites. The total score is the sum of the individual scores from all 17 sites, ranging from 0 (normal) to 51 (severe).
Baseline, Week 52
Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52.
Time Frame: Baseline, Week 52
The Health Assessment Questionnaire Disability Index (HAQ-DI) is a widely used tool to measure a patient's level of functional ability and disability. It consists of 20 questions that cover eight domains of daily living activities: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each question is rated on a scale from 0 (without difficulty) to 3 (unable to do).
Baseline, Week 52
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to end of study, assessed up to approximately 5 years
The distribution of adverse events will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.
Up to end of study, assessed up to approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 29, 2024

Primary Completion (Estimated)

November 30, 2028

Study Completion (Estimated)

August 30, 2032

Study Registration Dates

First Submitted

October 22, 2024

First Submitted That Met QC Criteria

October 22, 2024

First Posted (Actual)

October 24, 2024

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CYTB323K12201
  • 2023-510380-34-00 (Other Identifier: CTIS number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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