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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
96
single infusion of rapcabtagene autoleucel
rituximab intravenous infusion (i.v.) as per protocol
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%).
Time frame: Week 52
Change from baseline in Forced Vital Capacity (FVC)% predicted at Week 52
Change from baseline in FVC % predicted
Time frame: Baseline, Week 52
Change from baseline in modified Rodnan Skin Score (mRSS) at 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).
Time frame: Baseline, Week 52
Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at 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).
Time frame: Baseline, Week 52
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
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UCLA
Los Angeles, California, United States
RECRUITINGUCSF
San Francisco, California, United States
RECRUITINGUCSF
San Francisco, California, United States
RECRUITINGSutter Health Network
San Pablo, California, United States
RECRUITINGFL Medical Clinic Orlando Health
Zephyrhills, Florida, United States
RECRUITINGNorthwestern University
Chicago, Illinois, United States
RECRUITINGUniversity Of Iowa
Iowa City, Iowa, United States
RECRUITINGBoston Medical Center
Boston, Massachusetts, United States
RECRUITINGMichigan Med University of Michigan
Ann Arbor, Michigan, United States
RECRUITINGUniversity of Minnesota
Minneapolis, Minnesota, United States
RECRUITING...and 70 more locations
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.
Time frame: Up to end of study, assessed up to approximately 5 years