MTS109 in Patients With Refractory Autoimmune Diseases

NCT07526350 | Recruiting Early Phase 1 DMC

• 1 other identifier: MTS109-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is the first-in-human trial of MTS109 (mRNA-LNP). The goal of this clinical trial is to evaluate the safety, tolerability of intravenous injection of MTS109 in moderate to severe autoimmune diseases.

Conditions

Idiopathic Inflammatory Myopathies; Systemic Sclerosis (SSc); ANCA-Associated Vasculitis (AAV); Sjogren's Syndrome (SS); Systemic Lupus Erythematosus

Keywords

MTS109

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AE) of Grade ≥3

  Proportion of subjects with adverse events (AEs) of Grade ≥3 within 28 days after the last dose.

  Within 28 days after the last dose

• Incidence of treatment-emergent adverse events (TEAE)

  Incidence of TEAEs

  Within 28 days after the last dose

Secondary Outcomes (13)

• Response rate

  At Months 1, 2, 3, and 6

• Short-Form 36-item survey (SF-36)

  At Months 1, 2, 3, and 6

• Adverse events and injection site adverse reactions

  From the signing of informed consent up to 2 years after dosing

• Time to peak (Tmax)

  32 days after the first dose

• Peak concentration (Cmax)

  32 days after the first dose

Study Arms (1)

MTS109

EXPERIMENTAL

Drug: MTS109

Interventions

MTS109 DRUG

Three subcutaneous injections will be administered on Days 1, 4, and 7. A low-dose priming approach will be used to gradually reach the target therapeutic dose. Another three subcutaneous injections with the highest escalated dose will be given on Days 14, 21, and 28 (i.e., Week 4 after the first administration).

MTS109

Eligibility Criteria

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

You may qualify if:

• \) The subject or his/her legal representative has voluntarily signed a written informed consent form and is willing and able to comply with study procedures. 2) Aged 18 to 65 years (inclusive) at the time of signing the informed consent form, with no gender restriction.
• \) Subjects with SLE must meet the following criteria: a) Meet the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE); b) SLEDAI-2K score ≥6, with at least 1 BILAG-2004 organ domain score of Grade A (severe manifestation) or 2 Grade B (moderate manifestation), or both; or SLEDAI-2000 score ≥8; c) Meet the definition of refractory and relapsing disease: inadequate response to conventional therapy for more than 6 months, or disease flare after remission. Conventional therapy is defined as: glucocorticoids plus at least 2 of the following immunomodulatory agents: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and telitacicept.
• \) Subjects with idiopathic inflammatory myopathy (IIM) must meet the following criteria: a) Meet the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies (including dermatomyositis \[DM\], polymyositis \[PM\], anti-synthetase syndrome \[ASS\], and necrotizing myopathy \[NM\]); b) Positive for myositis-specific antibodies; c) Moderate-to-severe IIM during screening, defined as: MMT-8 ≥142 with active interstitial lung disease (ILD) (ground-glass opacity on HRCT); OR MMT-8 \<142 and at least 2 of the following: Physician's Global Assessment (PGA, VAS) ≥2 cm (10-cm VAS scale); Patient's Global Assessment (PtGA, VAS) ≥2 cm (10-cm VAS scale); Health Assessment Questionnaire Disability Index (HAQ-DI) \>0.25; One or more muscle enzymes (CK, LDH, AST, ALT) ≥1.5 × upper limit of normal (ULN); d) Meet the definition of refractory, relapsing, or progressive disease: Refractory: inadequate response to conventional therapy for more than 6 months, or disease flare after remission; conventional therapy as defined for SLE; Progressive: worsening myositis or rapidly progressive interstitial lung disease.
• \) Subjects with systemic sclerosis (SSc) must meet the following criteria: a) Meet the 2013 ACR classification criteria for systemic sclerosis; b) Positive for SSc-related specific antibodies; c) Meet the definition of refractory or progressive disease: Refractory: inadequate response to conventional therapy for more than 6 months, or disease flare after remission; conventional therapy as defined for SLE; Progressive: rapid skin progression (increase in mRSS \>25%); or progressive lung disease (decrease in FVC ≥10%, or decrease in FVC \>5% with decrease in DLCO ≥15%).
• \) Subjects with ANCA-associated vasculitis (AAV) must meet the following criteria: a) Meet the 2022 ACR/EULAR classification criteria for ANCA-associated vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis; b) Positive for ANCA-associated antibodies (MPO-ANCA or PR3-ANCA); c) Birmingham Vasculitis Activity Score (BVAS) ≥15 (total score 63), indicating active vasculitis; d) Meet the definition of refractory: inadequate response to conventional therapy for more than 6 months, or disease flare after remission; conventional therapy as defined for SLE.
• \) Subjects with Sjögren's syndrome (SS) must meet the following criteria: a) Meet the 2002 AECG criteria for primary Sjögren's syndrome or the 2016 ACR/EULAR classification criteria; b) Disease activity ESSDAI ≥6; c) Positive for anti-SSA/Ro antibody; d) Meet the definition of refractory: inadequate response to conventional therapy for more than 6 months, or disease flare after remission; conventional therapy as defined for SLE.
• \) Screening laboratory results meet the following criteria (excluding abnormalities related to the study disease): a) Neutrophil count ≥1.5 ×10⁹/L; b) Hemoglobin ≥80 g/L; platelet count ≥50 ×10⁹/L; c) Alanine aminotransferase (ALT) ≤3 × ULN; aspartate aminotransferase (AST) ≤3 × ULN (unless elevation is judged by the investigator to be related to PM or DM); total bilirubin (TBIL) \<2 × ULN (for subjects with Gilbert syndrome, direct bilirubin \[DBIL\] ≤1.5 × ULN); d) Creatinine clearance ≥30 mL/min; e) Activated partial thromboplastin time (APTT) ≤1.5 × ULN; prothrombin time (PT) ≤1.5 × ULN; f) Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%, with no clinically significant electrocardiogram (ECG) abnormalities; g) Baseline oxygen saturation \>92% while breathing room air.
• \) Female subjects of childbearing potential: negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
• \) Male subjects with female partners and female subjects of childbearing potential agree to use effective contraceptive methods (e.g., oral contraceptives, intrauterine device, condom) from screening until at least 1 year after the last dose of MTS109.

You may not qualify if:

• SLE subjects: a) Drug-induced SLE; b) Subjects with lupus crisis, or who require medications prohibited by the protocol due to comorbidities, or who are considered ineligible by the investigator.
• SSc subjects: a) Uncontrolled severe pulmonary arterial hypertension (PAH) related to SSc; b) Rapidly progressive lower gastrointestinal tract (small and large intestine) involvement related to SSc requiring parenteral nutrition; active gastric antral vascular ectasia; c) Uncontrolled or rapidly progressive ILD with oxygen saturation (SaO2) \<92% on room air; or requiring mechanical ventilatory support within 1 year prior to signing informed consent.
• AAV subjects: a) Crescentic glomerulonephritis, acute polyneuritis, or central nervous system (CNS) involvement other than AAV at screening; b) Life-threatening severe vasculitis (including diffuse alveolar hemorrhage, respiratory failure, intestinal perforation or massive bleeding, cerebral vasculitis, cardiac vasculitis, etc.); c) Secondary vasculitis (e.g., SLE, Henoch-Schönlein purpura, drug-induced, malignancy-associated, infection-induced, primary immunodeficiency, etc.).
• SS subjects: a) Poorly controlled severe systemic primary Sjögren's syndrome (pSS) manifestations at baseline that, in the investigator's assessment, may place the subject at excessive risk; b) Secondary Sjögren's syndrome with other confirmed autoimmune diseases (e.g., rheumatoid arthritis, SLE, scleroderma, inflammatory bowel disease); c) Subjects requiring regular use of medications known to cause dry mouth/dry eye as common major side effects; d) Subjects with other diseases that may interfere with efficacy assessment of primary Sjögren's syndrome, such as inflammatory bowel disease, gout, sarcoidosis, amyloidosis, IgG4-related disease, etc. All subjects:
• Subjects with a history of severe hypersensitivity or anaphylaxis;
• Subjects with contraindications or hypersensitivity to any component of the investigational product;
• Subjects with any of the following cardiac diseases: a) New York Heart Association (NYHA) Class III or IV congestive heart failure; b) Myocardial infarction or coronary artery bypass grafting within 6 months prior to screening; c) Clinically significant ventricular arrhythmia at screening, history of unexplained syncope not due to vasovagal reaction or dehydration, corrected QT interval (QTc) \>480 ms, or history of severe non-ischemic cardiomyopathy;
• Subjects with any active malignancy or history of malignancy within 5 years prior to screening, excluding: early-stage tumors treated with curative intent (carcinoma in situ or Stage I tumor, non-ulcerated primary melanoma \<1 mm depth without lymph node involvement), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, or breast carcinoma in situ treated with potentially curative therapy;
• Subjects with any other known autoimmune disease other than the study disease;
• Subjects requiring long-term use of anticoagulants affecting coagulation function;
• Subjects with clinically significant bleeding symptoms or obvious bleeding tendency within 6 months prior to screening, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.; hereditary or acquired bleeding and thrombotic tendency (e.g., hemophilia, coagulopathy, hypersplenism, etc.); subjects with arterial or venous thrombotic events within 6 months prior to screening, such as cerebrovascular disease (including cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis and/or pulmonary embolism;
• Subjects with any severe underlying disease at screening, e.g.: a) Evidence of uncontrolled infection or viral, bacterial, fungal, or other infection treated with systemic intravenous antibiotics; b) Evidence of clinically significant dementia or altered mental status; c) History of any other central nervous system disease or neurodegenerative disease, such as epilepsy, seizure, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychosis;
• Subjects with positive screening results for any of the following: a) Positive human immunodeficiency virus (HIV) antibody; b) Positive hepatitis B surface antigen (HBsAg); or positive hepatitis B core antibody (HBcAb) with HBV-DNA above the lower limit of detection of the assay; c) Positive hepatitis C virus (HCV) antibody with HCV RNA above the lower limit of detection of the assay; d) Active syphilis (excluding false-positive due to disease);
• Subjects with positive plasma cytomegalovirus (CMV) DNA or plasma Epstein-Barr virus (EBV) DNA (viral active);
• Subjects with active tuberculosis or untreated latent tuberculosis prior to screening;

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• Metis Techbio: collaborator

Study Sites (1)

Shanghai ChangZheng Hospital

Shanghai, Shanghai Municipality, 200003, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Myositis; Scleroderma, Systemic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Sjogren's Syndrome

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Huji Xu

CONTACT

86 021-81885514; huji_xu@tsinghua.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician, Head of the Department of Rheumatology and Immunology, Shanghai Changzheng Hospital

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 13, 2026
• Study Start: March 24, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)