An Exploratory Clinical Study Evaluate the Safety and Efficacy of Universal Universal Allogeneic CAR-T Cells Targeting CD19 and BCMA in the Treatment of B Cell-Related Autoimmune Disease

Plain English Summary

Allogeneic CD19/BCMA CAR-T for B Cell-Related Autoimmune Disease is a Phase 1 clinical trial sponsored by The Children's Hospital of Zhejiang University School of Medicine studying Autoimmune Diseases, Systemic Lupus Erthematosus (SLE), Multi-Drug Resistant Nephrotic Syndrome, IgA Nephropathy (IgAN), Systemic Sclerosis (SSc), ANCA Associated Systemic Vasculitis. This study tests a new type of cell therapy called CAR-T for adults and children with severe autoimmune diseases that haven't responded to other treatments. It is for patients with specific conditions like lupus, certain kidney diseases, and vasculitis that are resistant to standard therapies. Participants will receive a single infusion of the therapy after a preparation treatment, and will be closely monitored for up to two years. Alternative treatments include ongoing standard immunosuppressive drugs, steroids, and other targeted therapies, depending on the specific autoimmune condition. The trial aims to enroll 15 participants.

Official Summary

This is an exploratory, open-label, single-arm Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219C. QT-219C is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219C .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 5 and older with specific autoimmune conditions like lupus, nephrotic syndrome, IgA nephropathy, systemic sclerosis, or ANCA-associated vasculitis. Must have tried and failed at least two standard treatments, or have severe disease that hasn't improved. Patients must have adequate organ function (bone marrow, liver, kidney, heart, lungs) and be able to provide informed consent. Exclusion criteria include recent macrophage activation syndrome, certain active central nervous system lupus symptoms, and specific kidney biopsy findings for some conditions. This trial is studying Autoimmune Diseases, Systemic Lupus Erthematosus (SLE), Multi-Drug Resistant Nephrotic Syndrome, IgA Nephropathy (IgAN), Systemic Sclerosis (SSc), ANCA Associated Systemic Vasculitis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes will show how safe the treatment is by tracking side effects and serious reactions, and will assess if the therapy helps improve the disease within 90 days. The specific primary outcome measures are: Incidence of Dose-Limiting Toxicities (DLTs) (Day 0 to Day 28 post-infusion.); Incidence of Adverse Events (AEs) (Up to Day 90 post-infusion.); Preliminary Clinical Efficacy at Day 90 (Day 90 post-infusion.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial explores a novel CAR-T cell therapy that targets B cells, aiming to provide a new treatment option for patients with severe, treatment-resistant autoimmune diseases where current options ar This research targets Autoimmune Diseases, Systemic Lupus Erthematosus (SLE), Multi-Drug Resistant Nephrotic Syndrome, IgA Nephropathy (IgAN), Systemic Sclerosis (SSc), ANCA Associated Systemic Vasculitis, where improved treatment options are needed.

Investor Insight

This Phase 1 study represents an early-stage investment in a potentially groundbreaking therapy for autoimmune diseases, a large market with significant unmet needs, though approval probability is low Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of CAR-T therapy for your condition, and what to expect during and after treatment. Participation involves receiving a preparation regimen followed by a one-time infusion of the study drug, and requires regular follow-up visits for monitoring. Be prepared for potential side effects like fever, fatigue, and infections, and the need for close medical supervision during the study. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 15 participants

Interventions

• BIOLOGICAL: UCAR T-cell — A universal allogeneic CAR-T cell product targeting both CD19 and BCMA

Primary Outcomes

• Incidence of Dose-Limiting Toxicities (DLTs) (Day 0 to Day 28 post-infusion.)
• Incidence of Adverse Events (AEs) (Up to Day 90 post-infusion.)
• Preliminary Clinical Efficacy at Day 90 (Day 90 post-infusion.)

Secondary Outcomes

• Cmax of CAR-T cells [PK parameter] (Within 28 Days After UCAR T-cell Infusion)
• Tmax of CAR-T cells [PK parameter] (Within 28 Days After UCAR T-cell Infusion)
• AUC 0-28d of UCAR-T cells [PK parameter] (Within 28 Days After UCAR T-cell Infusion)
• The degree of B cell depletion [PD parameter] (Up to 12 Months After UCAR T-cell Infusion)
• The concentration levels of IL-6 [PD parameter] (Up to 12 Months After UCAR T-cell Infusion)

Full Eligibility Criteria

Inclusion Criteria:

* Common Inclusion Criteria:
* 1.Major organ function must meet the following criteria (exceptions allowed for abnormalities related to autoimmune disease activity):
* 1)Bone Marrow Function: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; b. Hemoglobin ≥ 60 g/L; c. Platelet count ≥ 30 × 10⁹/L.
* 2)Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
* 3)Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR \< 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
* 4)Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
* 5)Pulmonary Function: No severe pulmonary disease, and SpO₂ ≥ 92%.
* 2.Women of childbearing potential must use medically acceptable contraception or practice abstinence during the study treatment period and for at least 12 months after the end of study treatment.
* 3.Informed consent: The participant (and guardian if the participant is a minor) must provide written informed consent, indicating understanding of the study purpose and procedures and willingness to participate.
* Disease-Specific Inclusion Criteria
* SLE:
* 1.Age ≥ 5 years.
* 2.Meets the 2012 SLICC or 2019 EULAR/ACR classification criteria for SLE.
* 3.Must meet at least one of the following adequate treatment conditions:
* 1)Active disease persists despite adequate treatment with glucocorticoids (≥1 mg/kg/day prednisone or equivalent dose of other corticosteroids) in combination with at least two immunosuppressants or biologic agents for at least 3 months, or affected organ function has failed to improve; or inability to taper glucocorticoid dosage to ≤5 mg/day after 6 months of conventional treatment;
* 2)Patients who have developed intolerable drug toxicity during conventional therapy, or have contraindications precluding standard treatment, or have experienced multiple treatment failures-may be considered for enrollment following full informed consent by the investigator and the patient or legal guardian;
* 3)SLEDAI-2K Criteria: SLEDAI-2K score ≥8; or SLEDAI-2K score ≥6 combined with at least one BILAG-2004 Category A or two Category B organ system involvements (or both).
* 4.No occurrence of macrophage activation syndrome within 1 month prior to screening.
* 5.Occurrence of CNS lupus symptoms requiring intervention within 60 days prior to screening, including seizures, psychosis, cerebrovascular events, etc.
* MDR-SRNS
* 1.Age ≥3 years old, gender unlimited.
* 2.Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes #KDIGO# Guidelines;
* 3\. Must meet at least one of the following adequate treatment conditions:
* a) have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission(at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus, Other replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab).
* b) if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin- inhibitor. The researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.
* c) Patients unable to tolerate conventional therapy may be eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant (or guardian if minor) provides fully informed consent.
* d) Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks, and the patient or guardian has fully informed consent.
* 4.Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
* IgA nephropathy
* 1\. Age: ≥ 5 years old, gender unlimited;
* 2\. IgA nephropathy pathologically confirmed by renal biopsy;
* 3\. Angiotensin-Converting Enzyme Inhibitors (ACEI) or angiotensin receptor blocker (ARB) treated for at least 3 months and meet at least one of the following requirements:
* a) Combination or sequential treatment with steroids and at least one immunosuppressant or biologic for ≥ 3 months; and 24-hour urine protein quantification ≥500mg or UPCR≥0.5mg/mg;
* b) \>50% decline in eGFR within 3 months;
* c) Patients who are unable to toler

Trial Locations

• Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Frequently Asked Questions

Related Conditions

• Autoimmune Diseases
• Systemic Lupus Erythematosus (SLE)
• Nephrotic Syndrome
• IgA Nephropathy (IgAN)
• Systemic Sclerosis (SSc)
• ANCA Associated Systemic Vasculitis
• B Cell Lymphoma
• Leukemia
• Multiple Myeloma
• Rheumatoid Arthritis

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