Refractory Active Systemic Lupus Erythematosus
Conditions
Keywords
ACG102-001
Brief summary
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)
Detailed description
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)
Interventions
DRUGACG102 Injection
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.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) | Within 21 days after first dose | 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 |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first dose through Week 52 | Percentage of participants experiencing TEAEs, SAEs, and Adverse Events of Special Interest (AESIs) graded per NCI CTCAE v5.0 and ASTCT consensus criteria |
| Incidence of Treatment-Emergent Clinical Laboratory Abnormalities | Up to 52 weeks post first dose | Number of participants with clinically significant shifts from baseline in safety laboratory assessments (hematology, liver enzymes, coagulation, and vital sign) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in SLE disease activity scores | baseline and up to Week 52 post first dose | 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) |
| Change from Baseline in BILAG-2004 Score | pre-dose and up to 52 weeks post the first dose | 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) |
| Change from Baseline in Physician's Global Assessment (PGA) Score | pre-dose and up to 52 weeks post first dose | Change from baseline will be calculated as the score at each post-baseline visit minus the score at baseline of PGA score |
| Composite efficacy response rates | baseline and up to Week 52 post first dose | Proportion of participants achieving the SLE Responder Index-4 (SRI-4) response |
| Change from baseline in SF-36 score | baseline and up to Week 52 post first dose | Change from baseline in 36-Item Short-Form Health Survey (SF-36) score. |
| Change from baseline in renal parameters | Baseline and up to Week 52 post first dose | 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 |
| Pharmacokinetic profiling | Baseline and up to 24 weeks post first dose | Quantification of Target mRNA Expression Levels in Biological Samples via RT-qPCR. |
| Pharmacokinetics measurement | baseline and up to 24 weeks post first dose | Bioanalytical Quantification of Cationic Lipids and Major Metabolites using LC/MS |
| Pharmacodynamic Profiling | Baseline and up to 24 weeks post first dose | Serum concentrations of the TCE protein will be evaluated using a validated Enzyme-Linked Immunosorbent Assay (ELISA) |
| Pharmacodynamic biomarkers | Baseline and up to 52 weeks post first dose | Changes from baseline in serum IgG, IgM, IgA, anti-dsDNA antibodies, complement C3, and complement C4. |
| Immunogenicity | Baseline and up to 52 weeks post first dose | Percentage of participants who develop treatment-induced or treatment-enhanced ADAs and subsequent NAbs against ACG102 as determined by validated immunoassays. |
Contacts
CONTACTqiubai li, archiater
Outcome results
None listed