Systemic Lupus Erythematosus (SLE)
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of YK012 in participants with Moderate to Severe Systemic Lupus Erythematosus (SLE).
Detailed description
This clinical trial consists of Phase Ib and Phase II. Phase Ib consists of dose escalation stage and dose expansion stage. The main goal of dose escalation stage is to evaluate the safety and tolerability of YK012 in participants with Moderate to Severe Systemic Lupus Erythematosus (SLE), and the main goal of dose expansion stage is to evaluate the safety, tolerability and effectiveness in reducing disease activity of YK012 in participants with SLE. The main goal of phase II is to assess the efficacy of YK012 in participants with Moderate to Severe SLE. Pharmacokinetics, pharmacodynamics and immunogenicity of YK012 in participants are evaluated as secondary objectives in both phases.
Interventions
DRUGYK012
YK012 is a bispecific antibody targeting CD19 and CD3.
Sponsors
Excyte Biopharma Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 75 years (inclusive) at screening, regardless of sex * Meet the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, with a confirmed SLE diagnosis for at least 24 weeks at screening * Positive for anti-dsDNA antibody and/or antinuclear antibody (ANA) and/or anti-Smith antibody at screening, as determined using the local laboratory's reference ranges at the study site * Medium to high disease activity at screening, defined as: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥7 * Receiving stable background therapy at screening * Capable of understanding and voluntarily participating in this clinical trial, having provided written informed consent, and able to comply with scheduled visits, treatments, examinations, and other study procedures.
Exclusion criteria
* Known allergy to monoclonal antibodies or exogenous human immunoglobulins, or hypersensitivity to the investigational drug or any of its components * Received any anti-CD19/CD20 therapy or any B-cell depleting agents within 6 months prior to enrollment, or B-cell stimulatory factor inhibitors within 3 months or 5 half-lives prior to enrollment * Received TNF inhibitors, interleukin receptor blockers, other small molecules or biologics within 3 months or 5 half-lives prior to enrollment * Received intravenous immunoglobulins or plasmapheresis within 3 months prior to enrollment * Used traditional Chinese medicines/herbal preparations for SLE treatment containing within 2 weeks prior to enrollment * Received live or attenuated vaccines within 1 month prior to enrollment * Has other autoimmune diseases, inflammatory joint diseases, or skin disorders (other than SLE) that may interfere with disease activity assessment * History of malignancy within 5 years before screening, except for cured cases with no recurrence for at least 5 years, such as basal cell or squamous cell skin cancer, cervical carcinoma in situ, ductal carcinoma in situ of breast, or papillary thyroid cancer * Clinically significant cardiovascular/cerebrovascular diseases within 6 months prior to screening * Presence of QTcF interval prolongation on electrocardiogram (ECG) * Presence of poorly controlled hypertension at screening * History of non-SLE conditions requiring oral/intravenous/intramuscular/subcutaneous corticosteroid therapy (\>2 weeks) within 6 months prior to enrollment * Active tuberculosis at screening or untreated latent tuberculosis * History of solid organ or bone marrow transplantation * Presence of active infections * Lupus nephritis requiring protocol-prohibited medications as assessed by the investigator * Uncontrolled lupus crisis within 8 weeks prior to screening * History of central nervous system (CNS) disorders * Presence of clinically unstable or uncontrolled medical conditions at screening * Presence of clinically significant abnormal laboratory test results * Presence of active viral infections (e.g., hepatitis B, hepatitis C, HIV, or active syphilis) * Had major surgery within 4 weeks prior to enrollment or planned during study; * Participation in other interventional clinical trials within 4 weeks prior to enrollment * Pregnant or lactating women, or individuals with pregnancy plans during the study and within a specified period after treatment who are unwilling to use effective contraception * Other conditions deemed by investigators to preclude study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event (AE) | From the first infusion of YK012 to the end of trial at 48 weeks | An AE is defined as any untoward medical event that occurs after a participant receives the investigational drug, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the investigational drug. |
| Severe Adverse Event (SAE) | From the first infusion of YK012 to the end of trial at 48 weeks | An SAE refers to any untoward medical occurrence after the participant receives the IMP that results in one or more of the following: death, life-threatening event, permanent or serious disability or loss of function, hospitalization or prolongation of hospitalization, congenital abnormalities or birth defects. |
| Ib dose expansion stage and phase II: SRI-4 (Systemic Lupus Erythematosus Responder Index-4) response rates | From the first infusion of YK012 to the end of trial at 48 weeks | — |
| Ib dose escalation stage: Dose Limiting Toxicity (DLT) | From the first infusion of YK012 to Day 28 post first infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Concentration (Cmax) of YK012 | From pre-dose of YK012 to the end of trial at 48 weeks |
| Time to Reach Cmax (Tmax) | From pre-dose of YK012 to the end of trial at 48 weeks |
| Elimination Half Life (t1/2) | From pre-dose of YK012 to the end of trial at 48 weeks |
| Apparent Clearance (CL) | From pre-dose of YK012 to the end of trial at 48 weeks |
| Apparent volume of distribution (Vd) | From pre-dose of YK012 to the end of trial at 48 weeks |
| Minimum Concentration (Cmin) of YK012 | From pre-dose of YK012 to the end of trial at 48 weeks |
| Phase II: Characteristics of peripheral blood B-cell changes | From pre-dose of YK012 to the end of trial at 48 weeks |
| Change in urinary protein from baseline in patients with positive urinary protein during the trial | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in anti-dsDNA antibody level from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in complement C3 level from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in complement C4 level from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in IgG level from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in IgM level from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Changes in IgA levels from baseline | From pre-dose of YK012 to the end of trial at 48 weeks |
| Anti-Drug Antibody (ADA) positivity rate | From pre-dose of YK012 to the end of trial at 48 weeks |
| Neutralizing antibody (Nab) positivity rate | From pre-dose of YK012 to the end of trial at 48 weeks |
| Ib dose escalation stage: Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response rates | From screening to the end of trial at 48 weeks |
| BILAG-based Composite Lupus Assessment (BICLA) response rates | From screening to the end of trial at 48 weeks |
| Proportion of patients achieving disease remission as defined by Definition of Remission in SLE (DORIS) | From screening to the end of trial at 48 weeks |
| Proportion of patients achieving Lupus Low Disease Activity State (LLDAS) | From screening to the end of trial at 48 weeks |
| Proportion of patients with baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score ≥10 who achieved ≥50% improvement in CLASI (CLASI-50) during the trial | From screening to the end of trial at 48 weeks |
| Proportion of patients with baseline ≥4 swollen and/or tender joints who achieved ≥50% improvement in joint count during the trial | From screening to the end of trial at 48 weeks |
| Proportion and duration of patients with baseline glucocorticoid dosage >5mg/day prednisone (or equivalent) achieving dosage ≤5mg/day prednisone (or equivalent) | From screening to the end of trial at 48 weeks |
| Change in British Isles Lupus Assessment Group 2004 (BILAG-2004) score from baseline | From screening to the end of trial at 48 weeks |
| Change in Physician's Global Assessment (PGA) score from baseline | From screening to the end of trial at 48 weeks |
| Change in 36-Item Short Form Health Survey (SF-36) score from baseline | From screening to the end of trial at 48 weeks |
| Time to relapse after achieving Lupus Low Disease Activity State (LLDAS) during the trial | From screening to the end of trial at 48 weeks |
| Change in Fatigue Severity Scale (FSS) score from baseline | From screening to the end of trial at 48 weeks |
| Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline | From screening to the end of trial at 48 weeks |
| Area Under the Curve (AUC0-t) of a serum concentration versus time profile | From pre-dose of YK012 to the end of trial at 48 weeks |
| Area under the blood concentration-time curve from zero to infinity (AUC0-∞) | From pre-dose of YK012 to the end of trial at 48 weeks |
Countries
China
Contacts
CONTACTXiaofeng Zeng, Doctor of Medicine
Outcome results
None listed