CD19-targeted CAR-T (MC-1-50) for adults with refractory SLE

Phase I Clinical Trial of CD19-targeting Chimeric Antigen Receptor T Lymphocyte (MC-1-50) for the Treatment of Refractory Adult Systemic Lupus Erythematosus(SLE)

This trial will try a rapid-manufactured CD19-directed CAR-T cell therapy called MC-1-50 in adults whose SLE has not responded to standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: Beliuzumab, CAR-T, methotrexate, cyclophosphamide, prednisone
• Locations: 2 sites (Hefei, Anhui and 1 other locations)
• Trial ID: NCT06892145 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase I dose‑escalation and dose‑expansion trial testing safety, tolerability, cytodynamic effects and preliminary efficacy of MC-1-50 in refractory SLE. Participants receive a single infusion at one of three dose levels (0.3×10^5/kg, 1×10^5/kg, or 3×10^5/kg CAR-positive cells). The product is made on the PrimeCAR platform with about a 3-day manufacturing time and a high proportion of naïve T cells, designed to allow low-dose effective infusions and potentially improved safety. Results will be used to identify an appropriate dose regimen for a subsequent Phase II trial.

Who should consider this trial

Good fit: Adults (≥18) with active, refractory SLE (SLEDAI-2K ≥7) who remain symptomatic despite standard therapy including hydroxychloroquine, adequate glucocorticoids, other immunosuppressants, and at least one approved biologic are the intended participants.

Not a fit: Patients with well-controlled or low-activity SLE (SLEDAI <7), those with active infections, pregnancy, or severe organ dysfunction, or those unable to comply with site visits are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the therapy could reduce disease activity and lower reliance on chronic immunosuppression for people with refractory SLE.

How similar studies have performed: Small case series and early compassionate-use reports of CD19-directed CAR-T in refractory autoimmune diseases including SLE have shown promising remissions, but randomized or large-scale data are not yet available.

Eligibility criteria

Inclusion Criteria:

1. The patient or their guardian agrees to participate in this clinical trial and sign the ICF, indicating their understanding of the purpose and procedures of this clinical trial and willingness to participate in the study;
2. Age ≥ 18 years old , gender not limited;
3. Patients diagnosed with SLE according to the 2019 EULAR/ACR classification criteria,And by hydroxychloroquine, sufficient glucocorticoid (≥1mg/kg/d prednisone or equivalent amount of other hormones), to less than 2Treatment with immunosuppressants (including cyclophosphamide, motecophanate, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, etc.), and at least one approved biological agent (including titacept, Beliuzumab, etc.), with a total duration of treatment ≥3 months, still in a disease active state, or unable to tolerate conventional therapy;
4. SLEDAI-2K score ≥7 points;
5. Autoantibody test results are positive: ANA antibody positive and/or serum anti-DSDNA positive;
6. Adequate renal, hepatic, pulmonary and cardiac function defined as:

   1. Cardiac function: Echocardiography indicates left ventricular ejection fraction ≥ 50%;
   2. Renal function: serum creatinine ≤ 2.0 × ULN, or creatinine clearance rate ≥ 60ml/min (Cockcroft Gault formula);
   3. Hepatic function: ALT and AST ≤ 3.0 × ULN (may be relaxed to ≤ 3.0 × ULN in cases of combined liver infiltration);
   4. Total bilirubin ≤ 2.0 × ULN (Gilbert syndrome requires total bilirubin ≤ 3.0 × ULN);
   5. Pulmonary function: Blood oxygen saturation is ≥ 92% in non oxygen state.
7. No serious mental disorders;
8. Meet standards for apheresis or venous blood collection, and no other cell collection contraindications;
9. Women of childbearing age who have a negative blood pregnancy test and all subjects agree to use reliable and effective contraceptive methods (excluding safe period contraception) for contraception within one year after receiving MC-1-50 cell infusion from the time of signing the informed consent form. Including but not limited to: abstinence, implantable progestogen contraceptives that can inhibit ovulation; Intrauterine device (IUD); Intrauterine hormone release system; Spouse vasectomy; Compound hormone contraceptives that can inhibit ovulation (oral, vaginal, and transdermal); Progesterone contraceptives (oral or injectable) that can inhibit ovulation; When male subjects have sex with fertile women, they must agree to use barrier contraception (such as condom plus spermicidal foam/gel/film/emulsion/suppository). At the same time, participants should commit not to donate eggs (oocytes, oocytes) or sperm for assisted reproduction within one year after cell infusion.

Exclusion Criteria:

1. There were severe active central nervous system lupus that required therapeutic intervention at the time of screening;
2. Acute severe nephritis: had or was undergoing renal replacement therapy within 3 months prior to reinfusion, or had significant renal deterioration that the investigator believed was likely to cause the subject to require high doses of corticosteroids (prednisone ≥1mg/kg/ day or equivalent of other hormones), cyclophosphamide, or mycophanate during the first 3 months of the study;Clinical stable lupus nephritis that can be controlled during screening can be considered;
3. There were other lupus crises that were not controlled at the time of screening;
4. Individuals who have received CAR-T therapy or other gene modified cell therapies;
5. Combined with other autoimmune diseases requiring systemic treatment;
6. HBsAg or HBcAb positive and HBV DNA test greater than the normal range;HCV antibody positive and HCV RNA detection greater than the normal range;HIV antibody positive;Treponema pallidum antibody positive;
7. Suffered from any of the following heart diseases:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;
   2. Within the 6 months prior to enrollment, there has been a myocardial infarction, or a coronary artery bypass grafting (CABG) or stent implantation surgery has been performed;
   3. History of ventricular arrhythmias requiring treatment or unexplained syncope (excluding cases caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy;
8. Uncontrollable infection in the 1 weeks before enrollment;
9. History of solid organ transplantation or hematopoietic stem cell transplantation prior to screening；
10. Cerebrovascular accident or seizure occurred within 6 months prior to screening；
11. Deep vein or deep artery embolism event within the past 6 months prior to screening;
12. history of malignant neoplasms (other than tumors with no active lesion and ending treatment \> 2 years ago, and adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery);
13. (attenuated) Live vaccine ≤ 4 weeks prior to screening;
14. Have participated in other clinical trials within one month or five drug half lives (whichever is shorter) before enrollment;
15. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving MC-1-50 cell infusion;
16. Other situations considered by the investigator to be unsuitable to participate in the study.

Where this trial is running

Hefei, Anhui and 1 other locations

• The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) — Hefei, Anhui, China (Recruiting)
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Jing Xue, M.D.

Conditions Systemic Lupus Erythematosus; Refractory; CAR T-Cell therapy