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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 65 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06655896
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Novartis Pharmaceuticals
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Novartis Pharmaceuticals
Principal Investigator Affiliation	Novartis Pharmaceuticals
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, France, Germany, Israel, Italy, Japan, Netherlands, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Scleroderma, Diffuse

Additional Details

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.

Arms & Interventions

Arms

Experimental: rapcabtagene autoleucel arm

rapcabtagene autoleucel

Active Comparator: rituximab arm

rituximab

Interventions

Biological: - rapcabtagene autoleucel

single infusion of rapcabtagene autoleucel

Biological: - rituximab

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UCSF, San Francisco, California

Status

Recruiting

Address

UCSF

San Francisco, California, 94115

Site Contact

Zilan Zheng

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