A Study of BEN301 Injection in theTreatment of Autoimmune Diseases

NCT07527936 | Not Yet Recruiting Early Phase 1

• 1 other identifier: BEN301IIT1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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 BEN301 Injection 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.

Conditions

Systemic Sclerosis (SSc); Rheumatoid Arthritis (RA); Sjogren's Syndrome (SS); Idiopathic Inflammatory Myopathies(IIM)

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT)

  Proportion of participants experiencing dose- limiting toxicity (DLT) within 28 days after infusion, determination of the MTD or RP2D

  Days 28

• Adverse Event (AE)

  Incidence and proportion of adverse events occurring after infusion.

  AEs occuring from informed consent signing through Wek 12 post infusion. Thereafte, only AEs related to the investigational product will be collected through study completion, an average of 2 years.

Secondary Outcomes (4)

• Modified Rodnan Skin Score (mRSS)

  Week 12

• Simplified Disease Activity Index (SDAl) score

  Week 12

• EULAR Sjogren's Syndrome Disease Activity Index (ESSDAl) score

  Week 12

• Total Improvement Score (TIS)

  Week 12

Other Outcomes (1)

• Cytokine analysis

  Venous blood samples will be collected prior to infusion of BEN301 Injection and on Days 1, 3, 7, 10, 14,21, and Weeks 4, 8, 12, 16, 24, 48,and 96 post-infusion .

Study Arms (2)

BEN301 Low-dose group

EXPERIMENTAL

Single administration of 1x10\^8 viable CD4+CAR+ Foxp3+ cells.

Biological: Single administration of 1x10^8 viable CD4+ CAR+ Foxp3+ cells.

BEN301 High-dose group

EXPERIMENTAL

Single administration of 3x10\^8 viable CD4+CAR+ Foxp3+ cells

Biological: Single administration of 3x10^8 viable CD4+ CAR+ Foxp3+ cells.

Interventions

Single administration of 1x10^8 viable CD4+ CAR+ Foxp3+ cells. BIOLOGICAL

Lymphodepletion is generally not required; however, if Treg expansion issuboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m2 on day -3,or CTX 300 mg/m\^2 from day -5 to day -3); or cyclophosphamide combined with fludarabine (12.5-25 mg/m\^2 from day -5 to day -3); - or low-dose IL-2 administered after cell infusion.

BEN301 Low-dose group

Single administration of 3x10^8 viable CD4+ CAR+ Foxp3+ cells. BIOLOGICAL

Lymphodepletion is generally not required; however, if Treg expansion issuboptimal, lymphodepletion may be administered as needed, or low-dose IL-2 may be combined. The recommended lymphodepletion regimens include: Cyclophosphamide monotherapy (CTX 900-1000 mg/m2 on day -3,or CTX 300 mg/m\^2 from day -5 to day -3); or cyclophosphamide combined with fludarabine (12.5-25 mg/m\^2 from day -5 to day -3); - or low-dose IL-2 administered after cell infusion.

BEN301 High-dose group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Disease-Specific Criteria
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• 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: o Modified Rodnan Skin Score (mRSS) ≥ 10 and ≤ 35;
• Increase in mRSS ≥ 3 points compared to the most recent assessment within 6 months;o 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); ORForced 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).
• Rheumatoid Arthritis (RA)
• Diagnosis of RA according to the 1987 ACR or 2010 ACR/EULAR classification criteria.

You may not qualify if:

• 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.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.
• 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)).
• 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.
• 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.
• 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.
• 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: o Topical corticosteroids or topical immunomodulators (e.g., tacrolimus) for IIM-associated rash within ≤ 1 week prior to dosing;o JAK inhibitors within 2 weeks prior to dosing;o Cyclophosphamide, rituximab, or other anti-CD20 antibodies within 12 weeks prior to dosing;o Other investigational products within 4 weeks or 5 half-lives (whichever is longer) prior to dosing;o Combination therapy with \>1 immunosuppressant, \>1 antimalarial, or immunosuppressants plus antimalarials within 2 weeks prior to dosing.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Shanghai Jiaotong University School of Medicine, Renji Hospital

Shanghai, Shanghai Municipality, 200127, China

Location

MeSH Terms

Conditions

Scleroderma, Systemic; Arthritis, Rheumatoid; Sjogren's Syndrome; Myositis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Autoimmune Diseases; Immune System Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Qiong Fu, Dr

CONTACT

+86 13585603288; Fuqiong5@163.com

Shuang Ye, Dr

CONTACT

+86 15801706421; Yeshuang@renji.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-03

Locations

CN (1)