A Study of BEN301 Injection in the Treatment of Autoimmune Diseases

A Phase I Exploratory Study on the Safety and Efficacy of BEN301 Injection in the Treatment of Autoimmune Diseases

The study aims to investigate the safety, tolerability, and preliminary clinical efficacy of BEN301 Injection in patients with autoimmune diseases.

In patients with autoimmune diseases, Treg cells are typically deficient or dysfunctional. CAR-Treg cell therapy represents a promising strategy for the treatment of autoimmune diseases and may be applicable to a broad spectrum of autoimmune conditions. Preclinical studies have shown that BEN301Injection not only effectively suppresses the aberrant activation of T and B cells in SLE models, but also significantly reduces total lgG secretion and the production of SLE-specific autoantibodies, particularly anti-double-stranded DNA (dsDNA) antibodies. Moreover, no significant treatment-related toxicities were observed.

Treg cell therapy has already demonstrated favorable efficacy in multiple indications, including organ transplantation and autoimmune diseases, with a well-established safety and tolerability profile. Meanwhile, CAR-Treg cell therapy has been actively explored in various autoimmune conditions; several products have shown therapeutic potential, and some patients have already benefited from treatment. These findings highlight the promising prospects of CAR-Treg cell therapy in the management of autoimmune diseases.

Study Overview

• Status: Not yet recruiting
• Conditions: SSC RA SS IIM
• Intervention / Treatment: Biological: CD4⁺ CAR⁺ Foxp3⁺ cells; Biological: CD4⁺ CAR⁺ Foxp3⁺ cells

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yajing Zhang, PhD; Phone Number: +86 18601333856; Email: 23975701@qq.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Boren Hospital, Beijing.
      • Contact: Yajing Zhang, PhD; Phone Number: +86 18601333856; Email: 23975701@qq.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200127
      • Shanghai Jiaotong University School of Medicine, Renji Hospital
      • Contact: Qiong Fu, PhD; Phone Number: +86 13585603288; Email: Fuqiong5@163.com
      • Contact: Shuang Ye, PhD; Phone Number: +86 15801706421; Email: Yeshuang@renji.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. General Requirements

   • Voluntary participation in the study, providing written informed consent, and willingness and ability to comply with the protocol.
   • Age 18-70 years (inclusive) at the time of signing informed consent.
   • Expected survival ≥ 12 months.

2. Disease-Specific Criteria 1) Systemic Sclerosis (SSc)

   • Diagnosis of Systemic Sclerosis according to the 2013 ACR/EULAR Classification Criteria for SSc, with a total score ≥ 9.
   • Disease duration (defined as time from onset of first non-Raynaud's phenomenon manifestation) ≤ 6 years. If disease duration > 6 years at screening, the participant may be enrolled if the investigator determines potential benefit and following discussion with the medical monitor of the BEN301 manufacturing site.

   • Evidence of active disease at screening meeting at least one of the following criteria:

     • Modified Rodnan Skin Score (mRSS) ≥ 10 and ≤ 35;
     • Increase in mRSS ≥ 3 points compared to the most recent assessment within 6 months;
     • Increase in mRSS ≥ 2 points with involvement of a new body region compared to the most recent assessment within 6 months;
     • Increase in mRSS ≥ 1 point with involvement of two new body regions within 6 months;
     • Progressive Interstitial Lung Disease (ILD) meeting the following standards:

   Inadequate response or intolerance to at least one prior treatment (including cyclophosphamide, methotrexate, mycophenolate/mycophenolic acid, nintedanib, rituximab, or tocilizumab); AND at least one of the following:

   Evidence of progression on High-Resolution Computed Tomography (HRCT); OR Forced Vital Capacity (FVC) < 80% predicted, Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) < 80% predicted, evidence of FVC decrease (absolute) ≥ 10%, or FVC decrease 5%-9% with DLCO decrease ≥ 15%.

   • Inadequate response or intolerance to conventional therapies (glucocorticoids and immunosuppressants).

     2) Rheumatoid Arthritis (RA)

   • Diagnosis of RA according to the 1987 ACR or 2010 ACR/EULAR classification criteria.
   • Inadequate response, intolerance, or contraindication to at least one conventional synthetic DMARD (csDMARD) and at least one targeted synthetic DMARD (tsDMARD) or biologic DMARD (bDMARD), failing to achieve remission or low disease activity.
   • Moderate-to-severe active RA at screening, defined as ≥ 4 tender joints (of 68 assessed) and ≥ 4 swollen joints (of 66 assessed).
   • Erythrocyte Sedimentation Rate (ESR) > 28 mm/hr and/or C-reactive protein (CRP) > 10 mg/L.
   • Positive Rheumatoid Factor (RF) and/or Anti-Citrullinated Protein Antibody (ACPA).
   • Duration of RA diagnosis > 6 months. 3) Primary Sjögren's Syndrome (pSS)
   • Meets the 2016 ACR/EULAR Classification Criteria for Sjögren's Syndrome.
   • High disease activity index: ESSDAI ≥ 6 points.
   • Inadequate response or intolerance to conventional therapies (glucocorticoids and immunosuppressants).

   • Positive for Anti-Sjögren's Syndrome A (SSA/Ro) and/or Anti-Sjögren's Syndrome B (SSB/La) antibodies.

     4) Idiopathic Inflammatory Myopathies (IIM) / Dermatomyositis (DM) / Polymyositis (PM)

   • Suspected or confirmed diagnosis of Polymyositis (PM) or Dermatomyositis (DM) according to the 2017 EULAR/ACR Classification Criteria.

   • Moderate-to-severe PM or DM, defined as meeting both Part A and Part B below:

     • Part A: Manual Muscle Testing (MMT-8) total score < 142.
     • Part B: At least 2 of the following 5 items:

   Physician Global Assessment (PhGA, 10-cm VAS) ≥ 2 cm; Patient Global Assessment (PtGA, 10-cm VAS) ≥ 2 cm; Health Assessment Questionnaire-Disability Index (HAQ-DI) > 0.25; Elevation of any muscle enzyme (CK, LDH, AST, ALT) ≥ 1.3 × Upper Limit of Normal (ULN); Myositis Disease Activity Assessment Tool (MDAAT) global extramuscular activity (10-cm VAS) ≥ 2 cm.

   • Alternatively, presence of active disease: evidence of active muscle inflammation on MRI or muscle biopsy within 12 weeks.

3. Adequate Organ Function

   Within 7 days prior to screening (without transfusion, hematopoietic growth factors within 2 weeks, or medication correction):

   • Bone Marrow:

     • Hemoglobin (Hb) ≥ 80 g/L;
     • Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L;
     • Platelet count (PLT) ≥ 50 × 10⁹/L.
   • Renal Function: Creatinine Clearance (CrCl, calculated by Cockcroft-Gault formula, see Appendix 1) ≥ 50 mL/min (without hydration assistance).
   • Hepatic Function: Serum ALT and AST ≤ 2.5 × ULN (exceptions for CK-induced elevations may be determined by the investigator); Total bilirubin ≤ 1.5 × ULN.
   • Pulmonary Function: Oxygen saturation ≥ 92% on room air without supplemental oxygen; no clinically significant pleural effusion.
   • Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 40%; no pericardial effusion; ECG at screening showing no clinically significant abnormalities.
   • Coagulation: Fibrinogen ≥ 1.5 g/L; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Prothrombin Time (PT) ≤ 1.5 × ULN.

4. Biological Requirements

   • Presence of CD19+ B cells in peripheral blood.
   • Adequate venous access for leukapheresis, without contraindications to leukapheresis.

5. Reproductive Criteria

   • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening. (Women who are surgically sterile or postmenopausal for at least 2 years are considered non-childbearing).
   • Sexually active WOCBP and male participants must agree to use highly effective contraception from the time of signing informed consent until 1 year after the last study treatment, and must not donate eggs/sperm for assisted reproduction during this period.

Exclusion Criteria:

1. Severe Renal Disease

   • History of severe nephritis or nephrotic syndrome.

   • Severe is defined as:

     • Prior receipt of any of the following treatments within specified timeframes:

   Prior kidney transplantation; Dialysis or plasmapheresis within 3 months prior to screening; Glucocorticoid pulse therapy (defined as ≥500 mg/day prednisone or equivalent) within 1 month prior to screening.

   o Requirement for any of the following treatments during the study period: Use of prohibited medications per protocol; Need for dialysis or plasmapheresis; Need or planned kidney transplantation.

2. Severe Cardiovascular Disease

   • History of severe cardiovascular disease, including but not limited to: symptomatic chronic heart failure requiring intervention, acute myocardial infarction or coronary artery bypass grafting within 6 months, unstable angina, history of severe arrhythmia, or history of stroke.
   • New York Heart Association (NYHA) Class III-IV heart failure.
   • QTcF interval > 450 ms (male) or > 470 ms (female) on screening ECG (Fridericia formula: QTcF = QT / (RR^0.33)).

3. SSc-Specific Exclusions

   • Receipt of oral, intramuscular, or intravenous glucocorticoids (>10 mg/day prednisone or equivalent) within 1 week prior to leukapheresis. (Note: Investigators may consider dose reduction prior to leukapheresis/infusion provided the participant's disease is controlled).
   • Receipt of immunosuppressants within 1 week prior to leukapheresis, including but not limited to methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate, sirolimus, colchicine, or D-penicillamine.

4. RA-Specific Exclusions

   • Use of anti-TNF agents within 8 weeks prior to dosing (or 4 weeks for etanercept).
   • Use of any JAK inhibitor within 2 weeks prior to dosing.
   • Use of other biologics or non-B-cell depleting investigational drugs within fewer than 5 half-lives prior to dosing.

5. pSS-Specific Exclusions

   • Diagnosis of secondary Sjögren's syndrome (defined as overlap with other autoimmune or systemic inflammatory diseases, e.g., RA, SLE, scleroderma, or idiopathic inflammatory myopathy).

   • Severe systemic involvement assessed by the investigator, including:

     o Serious vasculitis involving kidneys, digestive system, heart, lungs, or CNS (excluding cutaneous vasculitis);

     o Active CNS or PNS involvement requiring high-dose glucocorticoids;

     o Severe renal involvement (e.g., GFR < 60 mL/min);

     o Severe pulmonary involvement (e.g., dyspnea at rest, or FVC < 60% or DLCO < 40%);

     o Myopathy requiring high-dose glucocorticoids;

     o Lymphoma.

   • Use of sodium hyaluronate eye drops, artificial tears, artificial saliva, or sialogogues (e.g., pilocarpine) within 7 days prior to dosing; use of immunosuppressants (e.g., cyclophosphamide, leflunomide, methotrexate, azathioprine) within 4 weeks prior to dosing; use of JAK inhibitors or other kinase inhibitors within 2 weeks prior to dosing; use of targeted biologics (e.g., Telitacicept, Belimumab, Abatacept, Adalimumab) within 6 weeks prior to dosing.
   • Requirement for medications causing dry mouth/dry eyes during the study.

6. IIM-Specific Exclusions

   • Participants with a record of Inclusion Body Myositis (IBM), juvenile myositis, drug-induced PM/DM, cancer-associated PM/DM (defined as cancer diagnosed within 3 years of PM/DM diagnosis), or non-inflammatory myopathies (e.g., muscular dystrophies).
   • Patients with PM/DM who have a high risk of malignancy.
   • Permanent muscle weakness due to causes other than PM/DM (e.g., stroke) as judged by the investigator.

   • Any of the following prior treatments/procedures:

     • Topical corticosteroids or topical immunomodulators (e.g., tacrolimus) for IIM-associated rash within ≤ 1 week prior to dosing;
     • JAK inhibitors within 2 weeks prior to dosing;
     • Cyclophosphamide, rituximab, or other anti-CD20 antibodies within 12 weeks prior to dosing;
     • Other investigational products within 4 weeks or 5 half-lives (whichever is longer) prior to dosing;
     • Combination therapy with >1 immunosuppressant, >1 antimalarial, or immunosuppressants plus antimalarials within 2 weeks prior to dosing.
7. Other Autoimmune Diseases • History of other autoimmune diseases excluding the target indications, including Eosinophilic Granulomatosis with Polyangiitis (EGPA), Henoch-Schönlein purpura, cryoglobulinemic vasculitis, anti-glomerular basement membrane disease, Behçet's disease, or Takayasu arteritis.

8. Malignancy

   • History of malignancy within 5 years prior to enrollment, including patients with tumor-associated PM/DM. Exceptions include: surgically removed and cured non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ of the breast, or patients cured with no evidence of recurrence in the past 2 years requiring no treatment.

9. Hypersensitivity

   • Known allergy, hypersensitivity, intolerance, or contraindication to BEN301 or any component of the study medications; or history of severe allergic reactions.

10. Prior Cell Therapy

    • Prior receipt of autologous/allogeneic hematopoietic stem cell transplantation or CAR-T cell therapy.

11. Recent Procedures/Vaccinations

    • Major surgery, live vaccine administration, or participation in other clinical trials within 1 month prior to screening.

12. Active Infection

    • Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to screening (prophylactic treatment excluded); active tuberculosis (excluded if T-SPOT positive).

13. Viral Serology

    • Positive serology for Hepatitis B (HBsAg positive regardless of HBV-DNA level), Hepatitis C (HCVAb positive), HIV (HIV antibody positive), or Syphilis (confirmed TPPA positive) at screening.

14. Prohibited Medications

    • Use of medications/treatments prohibited by the protocol during screening.

15. Investigator's Discretion • Any other condition deemed unsuitable for study participation by the investigator, such as certain psychiatric disorders, dementia, suicidal ideation, or poor compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEN301 Low-dose group; Single administration of 1×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells.	Biological: CD4⁺ CAR⁺ Foxp3⁺ cells; Single administration of 1×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells. Lymphodepletion is generally not required; however, if Treg expansion is suboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens 33 include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m² on day -3, or CTX 300 mg/m² from day -5 to day -3);; or cyclophosphamide combined with fludarabine (12.5-25 mg/m² from day -5 to day -3);; or low-dose IL-2 administered after cell infusion.; Biological: CD4⁺ CAR⁺ Foxp3⁺ cells; Single administration of 3×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells. Lymphodepletion is generally not required; however, if Treg expansion is suboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens 33 include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m² on day -3, or CTX 300 mg/m² from day -5 to day -3);; or cyclophosphamide combined with fludarabine (12.5-25 mg/m² from day -5 to day -3);; or low-dose IL-2 administered after cell infusion.
Experimental: BEN301 High-dose group; Single administration of 3×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells.	Biological: CD4⁺ CAR⁺ Foxp3⁺ cells; Single administration of 1×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells. Lymphodepletion is generally not required; however, if Treg expansion is suboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens 33 include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m² on day -3, or CTX 300 mg/m² from day -5 to day -3);; or cyclophosphamide combined with fludarabine (12.5-25 mg/m² from day -5 to day -3);; or low-dose IL-2 administered after cell infusion.; Biological: CD4⁺ CAR⁺ Foxp3⁺ cells; Single administration of 3×10⁸ viable CD4⁺ CAR⁺ Foxp3⁺ cells. Lymphodepletion is generally not required; however, if Treg expansion is suboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens 33 include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m² on day -3, or CTX 300 mg/m² from day -5 to day -3);; or cyclophosphamide combined with fludarabine (12.5-25 mg/m² from day -5 to day -3);; or low-dose IL-2 administered after cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Proportion of participants experiencing dose-limiting toxicity (DLT) within 28 days after infusion; determination of the MTD or RP2D	days 28
AE	Incidence and proportion of adverse events occurring after infusion.	AEs occurring from informed consent signing through Week 12 post-infusion. Thereafter, only AEs related to the investigational product will be collected through study completion, an average of 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Improvement Score (TIS)	Change from baseline in Myositis Response Criteria TIS scores at Week 12 after the first infusion of BEN301 Injection. The Total Improvement Score (TIS) is a standardized composite measure developed to quantify treatment response in idiopathic inflammatory myopathies(IIM). The TIS ranges from 0 to 100,with higher scores reflecting greater improvement.	Week 12
Cytokine analysis	Monitoring changes in peripheral blood cytokine levels before and after infusion of BEN301 Injection.	Venous blood samples will be collected prior to infusion of BEN301Injection and on Days 1, 3, 7, 10, 14,21, and Weeks 4, 8, 12, 16, 24, 48,and 96 post-infusion .
Modified Rodnan Skin Score (mRSS)	Change from baseline in modified Rodnan Skin Score (mRSS) at Week 12 after the first infusion of BEN301 Injection. The minimum value of the modified Rodnan skin scale (MRSS) is 0 points, and the maximum value is 51 points. The higher the score, the more severe the degree of skin sclerosis, that is, the worse the result. MRSS quantifies the skin involvement of systemic sclerosis by evaluating the skin hardness of 17 parts of the body. 0 points represent normal skin and 3 points represent severe thickening. The higher the total score, the more extensive and severe skin fibrosis, which is associated with disease activity and poor prognosis.	Week 12
Simplified Disease Activity Index (SDAl) score	SDAl score at Week 12 after the first infusion of BEN301 Injection; percentage of patients achieving SDAl low disease activity and clinical remission. SDAI score exceeding 26 is considered high disease activity; exceeding 11 and not greater than 26, moderate disease activity; exceeding 3.3 and not greater than 11, low disease activity.	Week 12
EULAR Sjogren's Syndrome Disease Activity Index (ESSDAl) score	Change from baseline in overall disease activity (ESSDAl) at Week 12 after the first infusion of BEN301 Injection. The ESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The ESSDAI includes 12 domains divided into 4 activity levels, where zero represents no activity. A higher score means a worse outcome.	Week 12

Collaborators and Investigators

• Sponsor: Beijing Boren Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 25, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 301IIT1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No