Recruiting NCT07010835

Study of YK012 in Moderate to Severe Systemic Lupus Erythematosus

Phase I / Phase II Interventional Systemic Lupus Erythematosus (SLE)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: YK012.
Who it may be relevant to: Registry conditions: Systemic Lupus Erythematosus (SLE). Basic parameters: 18 years — 75 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: China
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of YK012 in the Treatment of Moderate to Severe Systemic Lupus Erythematosus

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).

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

Drug YK012
YK012 is a bispecific antibody targeting CD19 and CD3.

Primary outcome measures

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) [Time frame: From the first infusion of YK012 to the end of trial at 48 weeks]
Severe Adverse Event (SAE) [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 outcome measures (12)

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]
Time to Reach Cmax (Tmax) [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Elimination Half Life (t1/2) [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Apparent Clearance (CL) [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Apparent volume of distribution (Vd) [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Minimum Concentration (Cmin) of YK012 [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Phase II: Characteristics of peripheral blood B-cell changes [Time frame: 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 [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Changes in anti-dsDNA antibody level from baseline [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]
Changes in complement C3 level from baseline [Time frame: From pre-dose of YK012 to the end of trial at 48 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: N/A
Model: Sequential
Masking: Open label
Primary purpose: Treatment

Study locations

China · 1 center

Peking Union Medical College Hospital — Beijing

Identifiers

NCT: NCT07010835 · YK012-4

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗