Study of YKST02 Alone or in Combination With YK012 in Patients With Active or Refractory Systemic Lupus Erythematosus

Official title

A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Preliminary Efficacy of YKST02 as Monotherapy or in Combination With YK012 in Patients With Active or Refractory Systemic Lupus Erythematosus

Overview

The purpose of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of YKST02 administered alone or in combination with YK012 in participants with active or refractory systemic lupus erythematosus (SLE). The main questions this study aims to address are: * Whether YKST02 alone or in combination with YK012 is safe and well tolerated in participants with active or refractory SLE * Whether YKST02 alone or in combination with YK012 demonstrates preliminary efficacy in treating SLE * What the PK and PD characteristics of YKST02 are when administered alone or in combination with YK012 * Whether treatment with YKST02 induces anti-drug antibody responses Participants will: * Receive intravenous infusions of YKST02 alone or in combination with YK012 according to the assigned cohort * Undergo safety assessments, including monitoring for adverse events * Provide blood samples for PK, PD, and immunogenicity analyses * Be followed for approximately 49 weeks to assess safety and efficacy

Detailed description

This is a single-center, open-label clinical trial evaluating YKST02 administered alone or in combination with YK012 in participants with active or refractory systemic lupus erythematosus (SLE). The study is designed to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy.

The study consists of two cohorts:

Cohort 1 (YKST02 Monotherapy):

Participants will receive YKST02 as a single agent to evaluate its safety, tolerability, and preliminary efficacy.

Cohort 2 (Combination Therapy):

Participants will receive YKST02 in combination with YK012. This cohort includes a dose-escalation phase to evaluate safety and tolerability across dose levels, followed by a dose-expansion phase to further evaluate safety and preliminary efficacy at selected dose levels.

The study includes a screening period, a treatment period during which participants receive study drugs by intravenous infusion, and a follow-up period for safety and efficacy assessments.

Safety evaluations include monitoring of adverse events, clinical laboratory tests, and other safety parameters. PK and PD assessments will be performed to characterize drug exposure and biological activity. Immunogenicity will be evaluated by assessing anti-drug antibody responses.

Exploratory analyses may include evaluation of immune cell populations, cytokines, and other biomarkers to further characterize the biological effects of the study treatments.

Interventions

• Drug YKST02
  YKST02 is administered by intravenous (IV) infusion.
• Drug YK012
  YK012 is administered by intravenous (IV) infusion in combination with YKST02.

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: From first dose through Day 35]
• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From first dose up to Week 49]

Secondary outcome measures (12)

• Pharmacokinetic (PK) Parameters [Time frame: From first dose up to Week 49]
• Changes in Peripheral B Cell and T Cell Populations [Time frame: From baseline up to Week 49]
• Change from Baseline in Urinary Protein [Time frame: From baseline up to Week 49]
• Change from Baseline in Anti-dsDNA Antibodies [Time frame: From baseline up to Week 49]
• Change from Baseline in Complement Levels (C3 and C4) [Time frame: From baseline up to Week 49]
• Change from Baseline in Immunoglobulin Levels (IgG, IgM, IgA) [Time frame: From baseline up to Week 49]
• Incidence of Anti-Drug Antibodies (ADA) [Time frame: From first dose up to Week 49]
• Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response Rate [Time frame: Weeks 12, 24, and 48]
• British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response Rate [Time frame: Weeks 12, 24, and 48]
• Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) Remission Rate [Time frame: Weeks 12, 24, and 48]
• Lupus Low Disease Activity State (LLDAS) Achievement Rate [Time frame: Weeks 12, 24, and 48]
• Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50) Response Rate [Time frame: Up to Week 49]

Eligibility criteria

Inclusion criteria

• Diagnosed with systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria, with active disease defined as SLEDAI-2K ≥6 at screening, and considered to have inadequate response, intolerance, or ineligibility to standard therapy.
• Have received standard therapy for SLE for at least 12 weeks prior to screening (including corticosteroids and at least one immunosuppressant and/or biologic agent), or are intolerant to or unsuitable for such therapies.
• Receiving stable background therapy prior to enrollment, including stable doses of corticosteroids (within 2 weeks prior to enrollment), and/or antimalarial agents or one immunosuppressant (within 4 weeks prior to enrollment).
• Positive for at least one lupus-related autoantibody at screening (e.g., anti-dsDNA, antinuclear antibody, or anti-Smith antibody).
• Able and willing to provide written informed consent and comply with study procedures.

Exclusion criteria

• Known hypersensitivity to monoclonal antibodies, immunoglobulins, or any component of the study drug.
• Prior treatment with B cell-depleting therapies, B cell-targeting biologics, or other biologic or targeted therapies within protocol-defined washout periods.
• Receipt of intravenous immunoglobulin or plasma exchange within protocol-defined washout periods.
• Receipt of live or attenuated vaccines within 4 weeks prior to enrollment.
• Presence of other active autoimmune diseases or inflammatory conditions (except secondary Sjögren's syndrome) that may interfere with assessment of SLE disease activity.
• History of major organ transplantation.
• History of malignancy within the past 5 years (except adequately treated low-risk cancers).
• Clinically significant or uncontrolled cardiovascular, cerebrovascular, neurological, hepatic, renal, hematologic, or metabolic diseases.
• Active or uncontrolled infections, including tuberculosis (active or untreated latent), hepatitis B or C, human immunodeficiency virus (HIV), or other clinically significant infections.
• Active or severe neuropsychiatric conditions that may interfere with study participation.
• Uncontrolled hypertension or clinically significant electrocardiogram abnormalities (including prolonged QT interval).
• Clinically significant abnormal laboratory findings at screening (e.g., severe cytopenias, impaired liver or renal function, or coagulation abnormalities).
• Recent major surgery or planned surgery during the study period.
• Recent use of investigational agents or participation in another clinical study within 4 weeks prior to enrollment.
• Pregnant or breastfeeding women, or women of childbearing potential unwilling to use effective contraception during the study and for an appropriate period after the last dose.
• Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07512947 · YKST02-YK012-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗