Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis
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.
Condition
- Scleroderma, Diffuse
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
- Masking Description
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental rapcabtagene autoleucel arm |
rapcabtagene autoleucel |
|
|
Active Comparator rituximab arm |
rituximab |
|
Recruiting Locations
San Francisco 5391959, California 5332921 94115
San Francisco 5391959, California 5332921 94115
San Pablo 5392508, California 5332921 94806
Zephyrhills 4178941, Florida 4155751 33542
Chicago 4887398, Illinois 4896861 60611
Iowa City 4862034, Iowa 4862182 52242
Boston 4930956, Massachusetts 6254926 02118
Ann Arbor 4984247, Michigan 5001836 48109 5271
Minneapolis 5037649, Minnesota 5037779 55455
Columbus 4509177, Ohio 5165418 43210
Portland 5746545, Oregon 5744337 97239
Sioux Falls 5231851, South Dakota 5769223 57105
Salt Lake City 5780993, Utah 5549030 84143
More Details
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
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.