A Clinical Study of ACG102 Injection in Patients With Refractory Active Systemic Lupus Erythematosus

Early Phase 1Not Yet RecruitingNCT07749430

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology13 enrolled

Overview

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of ACG102 administered via intravenous injection in patients with refractory active systemic lupus erythematosus (SLE)

A first-in-human, open label study to evaluate safety and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of multiple ascending dose ACG102 intravenously administered to adult participants with refractory active systemic lupus erythematosus (SLE)

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Refractory Active Systemic Lupus Erythematosus

Interventions

ACG102 InjectionDRUG

All enrolled participants will receive multiple intravenous infusions of ACG102 at the dose level assigned to their cohort. Dose levels and dosing schedules may be adjusted based on emerging safety, tolerability, and PK/PD data.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. ≥18 years of age at time of informed consent. 2. Diagnosis of systemic lupus erythematosus (SLE) fulfilling the 2019 EULAR/ACR classification criteria. 3. Refractory active disease defined as inadequate response to, or relapse following, standard of care (SoC) therapy. 4. Patients on a stable dose of SoC for at least 4 weeks prior to enrollment. 5. Sufficient organ function as defined by the protocol. Key Exclusion Criteria: 1. Active severe infection, including tuberculosis. 2. Severe hypogammaglobulinemia or IgA deficiency. 3. Active hepatitis or history of severe liver disease. 4. Severe cardiovascular diseases. 5. History of cancer within the past 5 years (with exceptions per protocol). 6. Receipt of B-cell-targeted therapies or other biologic therapies within the defined washout window prior to enrollment. 7. History of organ transplantation, bone marrow transplantation, or hematopoietic stem cell transplantation. 8. Known allergy to any active or inactive component of the study drug.

Outcomes

Primary Outcomes

Incidence of dose-limiting toxicities (DLTs)

Number and proportion of participants experiencing DLT. A DLT is defined as any treatment-emergent adverse event (TEAE) occurring within the 21-day DLT evaluation period post-infusion that meets protocol-specified criteria, graded per NCI CTCAE v5.0 and ASTCT consensus criteria for CRS and ICANS, and is considered at least possibly related to the study intervention

Time frame: Within 21 days after first dose

Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Percentage of participants experiencing TEAEs, SAEs, and Adverse Events of Special Interest (AESIs) graded per NCI CTCAE v5.0 and ASTCT consensus criteria

Time frame: From first dose through Week 52

Incidence of Treatment-Emergent Clinical Laboratory Abnormalities

Number of participants with clinically significant shifts from baseline in safety laboratory assessments (hematology, liver enzymes, coagulation, and vital sign)

Time frame: Up to 52 weeks post first dose

Secondary Outcomes

Change from baseline in SLE disease activity scores

Change from baseline will be calculated as the score at each post-baseline visit minus the score at baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

Time frame: baseline and up to Week 52 post first dose

Change from Baseline in BILAG-2004 Score

Change from baseline will be calculated as the total score at each post-baseline visit minus the score at baseline of the British Isles Lupus Assessment Group 2004 Index (BILAG-2004)

Time frame: pre-dose and up to 52 weeks post the first dose

Change from Baseline in Physician's Global Assessment (PGA) Score

Central Contacts

qiubai li, archiater

CONTACT

027-85726808 liqiubai_hust@hust.edu.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Change from baseline will be calculated as the score at each post-baseline visit minus the score at baseline of PGA score

Time frame: pre-dose and up to 52 weeks post first dose

Composite efficacy response rates

Proportion of participants achieving the SLE Responder Index-4 (SRI-4) response

Time frame: baseline and up to Week 52 post first dose

Composite efficacy response rates

Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)

Time frame: baseline and up to Week 52 post first dose

Composite efficacy response rates

Proportion of participants achieving the Definition Of Remission In SLE (DORIS).

Time frame: Baseline and up to Week 52 post first dose

Change from baseline in SF-36 score

Change from baseline in 36-Item Short-Form Health Survey (SF-36) score.

Time frame: baseline and up to Week 52 post first dose

Change from baseline in renal parameters

Urine protein will be quantified from a 24-hour urine collection at each scheduled visit, expressed in grams per 24 hours (g/24h). Change from baseline will be calculated as the value at each post-baseline visit minus the value at baseline

Time frame: Baseline and up to Week 52 post first dose

Change from baseline in renal parameters

Change from Baseline in Urine Protein-to-Creatinine Ratio (UPCR).Change from baseline will be calculated as the value at each post-baseline visit minus the value at baseline.

Time frame: Baseline and up to Week 52 post first dose

Change from baseline in renal parameters

Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) by CKD-EPI;Change from baseline will be calculated as the value at each post-baseline visit minus the value at baseline.

Time frame: baseline and up to Week 52 post first dose

Change from baseline in renal parameters

Proportion of participants with baseline proteinuria \>0.5 g/24h achieving proteinuria negativity.

Time frame: Baseline and up to Week 52 post first dose

Pharmacokinetic profiling

Quantification of Target mRNA Expression Levels in Biological Samples via RT-qPCR.

Time frame: Baseline and up to 24 weeks post first dose

Pharmacokinetics measurement

Bioanalytical Quantification of Cationic Lipids and Major Metabolites using LC/MS

Time frame: baseline and up to 24 weeks post first dose

Pharmacodynamic Profiling

Serum concentrations of the TCE protein will be evaluated using a validated Enzyme-Linked Immunosorbent Assay (ELISA)

Time frame: Baseline and up to 24 weeks post first dose

Pharmacodynamic biomarkers

Changes from baseline in serum IgG, IgM, IgA, anti-dsDNA antibodies, complement C3, and complement C4.

Time frame: Baseline and up to 52 weeks post first dose

Immunogenicity

Percentage of participants who develop treatment-induced or treatment-enhanced ADAs and subsequent NAbs against ACG102 as determined by validated immunoassays.

Time frame: Baseline and up to 52 weeks post first dose

Immunogenicity

Percentage of participants with detectable antibodies directed against the PEG component of the formulation, measured via validated serum assays.

Time frame: Baseline and up to 52 weeks post first dose