Systemic Lupus Erythematosus
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of IMC-002 and IMM0306S in the treatment of active SLE.
Detailed description
This two-stage study consists of a multicenter dose-escalation study（Phase Ib）and a multicenter randomized, double-blind, placebo-controlled study（Phase II）. Primary objectives of the dose-finding stage: 1) Evaluate the efficacy, safety, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of intravenous IMC-002 and subcutaneous IMM0306S in adult patients with active systemic lupus erythematosus (SLE); 2) Determine the absolute bioavailability of subcutaneous IMM0306S relative to intravenous IMC-002 in adults with moderate-to-severe active SLE; 3) Select the recommended Phase II dose (RP2D). Primary objectives of the proof-of-concept (PoC) stage: Compare the efficacy of 1.2 mg/kg or 1.6 mg/kg IMC-002 versus placebo in adults with moderate-to-severe active SLE, and assess the efficacy and population PK (popPK) profiles of IMM0306S in patients with active SLE.
Interventions
DRUGIMC-002 + SOC
intravenous injection of 0.8mg/kg、1.2mg/kg and1.6mg/kg
DRUGPlacebo + SOC
intravenous or subcutaneous injection of Placebo
DRUGIMM0306S + SOC
subcutaneous injection of 2.0 mg/kg，4.0 mg/kg and 6.0mg/kg
Sponsors
ImmuneCare Biopharmaceuticals (Shanghai) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Has had a diagnosis of SLE for at least 12 weeks prior to the screening Visit. * SLEDAI-2000 score ≥8. For screening eligibility only, headache and fever items shall be excluded from SLEDAI-2K scoring. Skin lesions shall meet morphological and distributive characteristics of active cutaneous lupus, with a total active Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) score ≥2. * BILAG-2004 organ system scores of at least 1 A or 2 B at screening. * Currently receiving at least one of the SOC SLE medications: oral corticosteroid, antimalarial and/or immunosuppressive agent. * Other protocol defined inclusion criteria may apply.
Exclusion criteria
* Active or unstable neuropsychiatric SLE or lupus nephritis * Autoimmune or rheumatic disease other than SLE * Significant, uncontrolled medical conditions not related to SLE * Active and/or severe viral, bacterial or fungal infection * History of malignancy within 5 years * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs and SAEs | week 52 | The proportion of patients with AEs and SAEs |
| Pharmacokinetics profiles | week 52 | To characterize PK profiles and absolute bioavailability. |
| SLE Responder Index (SRI-4) | week 24 | Proportion of patients achieving a response in SRI-4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serologic laboratory parameters | week 52 | Changes from baseline in serologic laboratory parameters (antinuclear antibodies, anti-ds-DNA antibodies, complement C3 and C4). |
| Pharmacodynamic (PD) assessments and biomarker evaluations | week 52 | Changes in TBNK subsets (CD3, CD4, CD56, CD16, Treg, etc.), B-cell subsets (CD19, CD20, CD27, CD38, CD24, etc.), IL-6 and IgG. |
| SLE Responder Index (SRI-4) | week 12 and 52 | Proportion of patients achieving a response in SRI-4 |
| Lupus Low Disease Activity State (LLDAS) | week 24 and 52 | Proportion of patients achieving a response in LLDAS. |
| Definition of Remission In SLE (DORIS) | week 24 and 52 | Proportion of patients achieving a response in DORIS. |
| Achieve and sustain a low dose of corticosteroid | week 52 | Changes in corticosteroid dosage at each visit and proportion of patients who achieve or maintain prednisone ≤ 7.5 mg/d. |
| SLEDAI-2000, PGA, BILAG-2004 and EQ-5D | week 52 | Changes from baseline in SLEDAI-2000, PGA, BILAG-2004 and EQ-5D. |
| Achieve low level of urine protein | week 52 | Changes in 24-hour urinary protein at each visit among trial patients with elevated 24-hour urinary protein at baseline (≥0.5 g) and proportion of patients who achieve to reduce urine protein level. |
| Immunogenicity profiles | week 52 | Positive rate and titers of anti-drug antibodies (ADA); neutralizing antibodies (NAb) may be further evaluated. |
Countries
China
Outcome results
None listed