rapcabtagene autoleucel: single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.
rituximab: rituximab intravenous infusion (i.v.) as per protocol
Study 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
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Achievement of a treatment response as per the Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) definition at Week 52. — 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%).
Trial sites (93)
Facility
City
Region
Status
UCLA
Los Angeles
California
UCSF
San Francisco
California
Sutter Health Network
San Pablo
California
FL Medical Clinic Orlando Health
Zephyrhills
Florida
Northwestern University
Chicago
Illinois
University Of Iowa
Iowa City
Iowa
Boston Medical Center
Boston
Massachusetts
Michigan Med University of Michigan
Ann Arbor
Michigan
University of Minnesota
Minneapolis
Minnesota
James Cancer Hospital
Columbus
Ohio
Oregon Health Sciences University
Portland
Oregon
Avera Cancer
Sioux Falls
South Dakota
LDS Hospital
Salt Lake City
Utah
Novartis Investigative Site
Córdoba
Córdoba Province
Novartis Investigative Site
CABA
Argentina
Novartis Investigative Site
Camperdown
New South Wales
Novartis Investigative Site
Darlinghurst
New South Wales
Novartis Investigative Site
Graz
Austria
Novartis Investigative Site
Vienna
Austria
Novartis Investigative Site
Vienna
Austria
Novartis Investigative Site
Ghent
Belgium
Novartis Investigative Site
Salvador
Estado de Bahia
Novartis Investigative Site
Curitiba
Paraná
Novartis Investigative Site
Barretos
São Paulo
Novartis Investigative Site
São Paulo
São Paulo
Novartis Investigative Site
São Paulo
São Paulo
Novartis Investigative Site
Olomouc
Czechia
Novartis Investigative Site
Prague
Czechia
Novartis Investigative Site
Aarhus N
Denmark
Novartis Investigative Site
Bordeaux
France
Novartis Investigative Site
Dijon
France
Novartis Investigative Site
Lille
France
Novartis Investigative Site
Lyon
France
Novartis Investigative Site
Montpellier
France
Novartis Investigative Site
Paris
France
Novartis Investigative Site
Rennes
France
Novartis Investigative Site
Strasbourg
France
Novartis Investigative Site
Freiburg im Breisgau
Baden-Wurttemberg
Novartis Investigative Site
Göttingen
Lower Saxony
Novartis Investigative Site
Leipzig
Saxony
+ 53 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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