Study of YK012 in Moderate to Severe Systemic Lupus Erythematosus

Phase 2RecruitingNCT07010835

Excyte Biopharma Ltd189 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

189

Conditions

Systemic Lupus Erythematosus (SLE)

Interventions

YK012DRUG

YK012 is a bispecific antibody targeting CD19 and CD3.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Ib dose escalation stage: Dose Limiting Toxicity (DLT)

Time frame: From the first infusion of YK012 to Day 28 post first infusion

Adverse Event (AE)

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.

Time frame: From the first infusion of YK012 to the end of trial at 48 weeks

Severe Adverse Event (SAE)

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.

Time frame: From the first infusion of YK012 to the end of trial at 48 weeks

Ib dose expansion stage and phase II: SRI-4 (Systemic Lupus Erythematosus Responder Index-4) response rates

Time frame: From the first infusion of YK012 to the end of trial at 48 weeks

Secondary Outcomes

Area Under the Curve (AUC0-t) of a serum concentration versus time profile

Time frame: 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-∞)

Time frame: From pre-dose of YK012 to the end of trial at 48 weeks

Maximum Concentration (Cmax) of YK012

Time frame: From pre-dose of YK012 to the end of trial at 48 weeks

Central Contacts

Xiaofeng Zeng, Doctor of Medicine

CONTACT

+86 13501069845 xiaofeng.zeng@cstar.org.cn

Data from ClinicalTrials.gov

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