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

Phase 1Not Yet RecruitingNCT07512947

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology30 enrolled

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

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.

Study Type

INTERVENTIONAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incidence of Dose-Limiting Toxicities (DLTs)

Number and proportion of participants experiencing dose-limiting toxicities (DLTs) as defined in the protocol.

Time frame: From first dose through Day 35

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number and proportion of participants experiencing adverse events (AEs) and serious adverse events (SAEs), graded according to CTCAE criteria.

Time frame: From first dose up to Week 49

Secondary Outcomes

Pharmacokinetic (PK) Parameters

Pharmacokinetic parameters of study drug, including maximum observed concentration and overall exposure.

Time frame: From first dose up to Week 49

Changes in Peripheral B Cell and T Cell Populations

Changes from baseline in peripheral blood B cells, T cells, and their subsets.

Time frame: From baseline up to Week 49

Change from Baseline in Urinary Protein

Change from baseline in urinary protein (24-hour urine protein) in participants with baseline proteinuria (\>0.5 g/24h).

Time frame: From baseline up to Week 49

Change from Baseline in Anti-dsDNA Antibodies

Change from baseline in anti-double stranded DNA (anti-dsDNA) antibody levels.

Time frame: From baseline up to Week 49

Change from Baseline in Complement Levels (C3 and C4)

Change from baseline in complement component C3 and C4 levels, analyzed and reported separately.

Time frame: From baseline up to Week 49

Change from Baseline in Immunoglobulin Levels (IgG, IgM, IgA)

Change from baseline in immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) levels

Time frame: From baseline up to Week 49

Incidence of Anti-Drug Antibodies (ADA)

Proportion of participants with treatment-emergent anti-drug antibodies (ADA); neutralizing antibodies may be assessed in ADA-positive participants.

Time frame: From first dose up to Week 49

Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response Rate

Proportion of participants achieving a response defined by the Systemic Lupus Erythematosus Responder Index-4 (SRI-4), a composite responder endpoint based on improvement in disease activity as assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), with no worsening in the British Isles Lupus Assessment Group 2004 index (BILAG-2004) and no clinically significant worsening in the Physician's Global Assessment (PGA).

Time frame: Weeks 12, 24, and 48

British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response Rate

Proportion of participants achieving a response based on the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), a composite responder endpoint based on predefined criteria including improvement in disease activity as assessed by the BILAG-2004 index, no worsening in other organ systems, and no clinically significant worsening in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician's Global Assessment (PGA).

Time frame: Weeks 12, 24, and 48

Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) Remission Rate

Proportion of participants achieving remission according to the Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) criteria, based on predefined clinical criteria including absence of clinical disease activity and low Physician's Global Assessment (PGA), with stable background therapy.

Time frame: Weeks 12, 24, and 48

Lupus Low Disease Activity State (LLDAS) Achievement Rate

Proportion of participants achieving low disease activity according to the Lupus Low Disease Activity State (LLDAS) criteria, based on predefined criteria including low overall disease activity, no new or worsening disease activity, and stable treatment.

Time frame: Weeks 12, 24, and 48

Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50) Response Rate

Proportion of participants with at least 50% improvement from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score among participants with baseline CLASI score ≥10.

Time frame: Up to Week 49

Joint Response Rate

Proportion of participants achieving improvement in joint counts.

Time frame: From baseline up to Week 49

Glucocorticoid Dose Reduction

Proportion of participants achieving reduction to ≤5 mg/day prednisone (or equivalent).

Time frame: Weeks 12, 24, and 48

Time to Disease Flare After Achieving LLDAS

Time from first achievement of LLDAS to disease flare.

Time frame: Up to Week 49

Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

Change from baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, a validated composite measure of disease activity ranging from 0 to 105, where higher scores indicate greater disease activity.

Time frame: From baseline up to Week 49

Change from Baseline in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)

Change from baseline in disease activity as assessed by the British Isles Lupus Assessment Group 2004 Index (BILAG-2004), a validated organ-based disease activity index that categorizes disease severity across organ systems using ordinal grades (A, B, C, D, and E), where A represents the highest level of disease activity and E represents no current disease activity.

Time frame: From baseline up to Week 49

Change from Baseline in Physician's Global Assessment (PGA)

Change from baseline in the Physician's Global Assessment (PGA) score, assessed using a 0 to 3 visual analogue scale, where higher scores indicate greater disease activity.

Time frame: From baseline up to Week 49

Change from Baseline in Patient-Reported Outcomes (Quality of Life and Fatigue)

Change from baseline in patient-reported outcomes, including: the 36-Item Short Form Health Survey (SF-36), a validated measure of health-related quality of life across multiple domains, with scores ranging from 0 to 100, where higher scores indicate better health status; the Fatigue Severity Scale (FSS), a validated measure of fatigue severity, with scores typically ranging from 1 to 7, where higher scores indicate greater fatigue.

Time frame: From baseline up to Week 49

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts