This multi-center, open-label, Phase 1/2 study aims to evaluate the safety, tolerability, and preliminary efficacy of C-CAR168, an autologous anti-CD20/BCMA CAR-T therapy, in patients with autoimmune diseases refractory to standard treatments. The study includes both dose escalation and dose expansion phases, with participants grouped into condition-specific cohorts. The purpose of this study is to: 1. Test the safety and ability for subjects with autoimmune refractory to standard treatment to tolerate the C-CAR168. 2. Determine the recommended Phase 2 dose of C-CAR168 in subjects with autoimmune disease refractory to standard treatment. Participants will be asked to: * Undergo screening to determine eligibility based on entry criteria. * Taper steroid use before leukapheresis. * Undergo leukapheresis for the manufacturing of C-CAR168. * Temporarily discontinue immunosuppressive therapy at least 7 days prior to leukapheresis. * Receive bridging therapy (steroids) if necessary to maintain disease stability during C-CAR168 manufacturing. * Undergo lymphodepletion therapy with fludarabine and cyclophosphamide. * Receive a single intravenous infusion of C-CAR168 at the assigned dose level on Day 0. * Attend regular safety and efficacy assessments for up to 24 months post-infusion. * Undergo dose-limiting toxicity evaluation during the first 28 days post-infusion (for those in the dose escalation phase). * Follow withdrawal procedures if necessary, including a discharge visit within 14 days if their condition deteriorates, unacceptable toxicity occurs, they no longer meet criteria, or they choose to withdraw.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
This is a multi-center, Phase 1/2, open-label, dose-escalation and dose-expansion study evaluating C-CAR168 for the treatment of autoimmune diseases refractory to standard therapy. A traditional 3+3 design is used to identify the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) in disease-specific cohorts.
AbelZeta, Inc.
Rockville, Maryland, United States
Incidence of Adverse Events or Dose Limiting Toxicities
The number and severity of Adverse Events (AE) and Serious Adverse Events (SAE), including dose limiting toxicities (DLTs) will be recorded.
Time frame: Up to 24 months
To evaluate the efficacy of C-CAR168
Proportion of subjects meeting the KDIGO 2024 Clinical Practice Guidelines' Definition of Remission, which includes complete response, primary efficacy renal response, or partial response.
Time frame: Up to 24 months
To evaluate the efficacy of C-CAR168
Proportion of subjects achieving SLEDAI-2K response over time.
Time frame: Up to 24 months
To evaluate the efficacy of C-CAR168
Proportion of subjects achieving British Isles Lupus Assessment Group (BILAG)(BILAG) response over time.
Time frame: Up to 24 months
Renal Related Events
Record any renal related events during the study, including disease flare and the time to the event.
Time frame: Up to 24 months
Time to Response
The number of days to response from the infusion of C-CAR0168 to the first recorded remission.
Time frame: Up to 24 months
Corticosteroid use
The number of patients who achieved a low dose of steroids or no longer require.
Time frame: Up to 24 months
To characterize the cellular kinetics of C-CAR168
Level of C-CAR168 positive cells in the blood.
Time frame: Up to 24 months
To assess immunogenicity of C-CAR168
Presence of C-CAR168 antibodies.
Time frame: Up to 24 months
To evaluate the efficacy of C-CAR168
Proportion of subjects whose for Physician Global Assessment (PGA) score does not worsen over time.
Time frame: Up to 24 months
To evaluate the efficacy of C-CAR168
Proportion of subjects achieving a predefined score on the Visual Analog Scale (VAS) at specified time points. Efficacy will be assessed by evaluating changes in pain intensity as perceived by subjects, using the Visual Analog Scale (VAS). Subjects will rate their pain intensity on a scale from 0 (no pain) to 10 (worst imaginable pain). This will provide a subjective measure of pain severity over the course of the study.
Time frame: Up to 24 months
To assess changes for reported health-related quality of life, overall health status
To assess changes from baseline for Functional Assessment of Chronic Illness Therapy (FACIT). The 13-item questionnaire will measure the level of fatigue and its impact on daily functioning. Higher scores reflect less fatigue and better overall energy levels.
Time frame: Up to 24 months
To assess changes for reported health-related quality of life, overall health status
To assess changes from baseline for SF-36 (Short Form Health Survey). Efficacy will be assessed by evaluating changes in quality of life using the SF-36. Higher scores indicate better overall health and quality of life.
Time frame: Up to 24 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.