Clinical trial NCT07010835: Study of YK012 in Moderate to Severe Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus (SLE)
Lead sponsor: Excyte Biopharma Ltd
Sponsor class: INDUSTRY
First posted: 2025-06-08
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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. The main goal of phase Ib is to evaluate the safety and tolerability of YK012 in participants with Moderate to Severe Systemic Lupus Erythematosus (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 paricipants are evaluated as secondary objectives in both phases

Eligibility criteria: Inclusion Criteria:

* Aged 18 to 65 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
* High disease activity at screening, defined as: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥7
* Receiving stable Standard of Care (SoC) at screening, including either oral glucocorticoid monotherapy at a stable dose (≤40 mg/day prednisone or equivalent) or combined with antimalarial drugs at a stable dose for at least 2 weeks prior to screening, or a single immunosuppressant at a stable dose for at least 4 weeks (only one immunosuppressant is permitted)
* 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 rituximab or any B-cell depleting agents within 6 months prior to enrollment, or B-cell stimulatory factor inhibitors (e.g., belimumab, telitacicept) within 3 months prior to randomization (subjects with B-cell counts above the lower limit of normal may be enrolled);
* Received TNF inhibitors, interleukin receptor blockers, other small molecules or biologics within 3 months prior to enrollment;
* Received intravenous immunoglobulins or plasmapheresis within 3 months prior to enrollment;
* Used Total Glucosides of White Paeony Capsules, Zhengqing Fengtongning, Colquhounia Root Tablets, Tripterygium wilfordii tablets, or other traditional Chinese medicines/herbal preparations containing Tripterygium wilfordii within 1 month prior to enrollment;
* Received live or attenuated vaccines within 1 month prior to enrollment;
* Has autoimmune diseases other than SLE (except secondary Sjögren's syndrome);
* History of malignancy, except for completely resected basal cell or squamous cell skin cancer, cervical carcinoma in situ, ductal carcinoma in situ of breast, or papillary thyroid cancer that has been disease-free for at least 5 years;
* Clinically significant cardiovascular/cerebrovascular diseases within 6 months prior to screening: The New York Heart Association Classification (NYHA) Class III or IV heart failure, unstable angina, myocardial infarction, severe arrhythmias, or stroke;
* 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;
* Active infections including: systemic antibiotic-treated infections within 2 weeks prior to enrollment; unresolved Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Herpes Simplex Virus (HSV),Varicella-Zoster Virus (VZV) infections;
* Within 8 weeks prior to enrollment: severe lupus nephritis (defined as proteinuria \>6g/24 hours or serum creatinine \>2.5mg/dL \[221μmol/L\]), active nephritis requiring protocol-prohibited medications, needing hemodialysis, or receiving prednisone ≥100mg/day (or equivalent) for ≥14 days;
* Within 8 weeks prior to enrollment: Central Nervous System (CNS) disorders (including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, CNS vasculitis) caused or not caused by SLE;
* Laboratory abnormalities defined as:

  * Marked hematological abnormalities
  * Abnormal liver function indicators
  * Impaired renal function
  * Notable immunological deviations
* Positive virology tests for:

  * HIV antibodies
  * HBsAg+; or HBsAg-/HBcAb+ with detectable HBV-DNA
  * HCV Ab+ with detectable HCV-RNA
  * Treponema pallidum antibodies+ (except if negative for Rapid Plasma Reagin or Toludine Red Unheated Serum Test);
* 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/lactating women; women of childbearing potential with positive pregnancy test; or subjects planning pregnancy within 12 months after study completion; unwilling to use ≥1 contraceptive method during the study and for 12 months thereafter;
* Other conditions deemed by investigators to preclude study participation.

Primary outcomes:
measure: Ib: Adverse Event (AE)
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks
measure: Ib: Severe Adverse Event (SAE)
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks
measure: II: SRI-4 (Systemic Lupus Erythematosus Responder Index-4) response rates
timeFrame: From the first infusion of YK012 to the end of the trial at 76 weeks
Secondary outcomes:
measure: Ib: Area Under the Curve (AUC0-t) of a serum concentration versus time profile
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Maximum Concentration (Cmax) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Time to Reach Cmax (Tmax)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Elimination Half Life (t1/2)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Total Apparent Clearance (CL)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Minimum Concentration (Cmin) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Maximum Steady-State Concentration (Css_max) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Minimum Steady-State Concentration (Css_min) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Average Steady-State Concentration (Css_av) of YK012
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Area Under the Curve Limited to the End of a Dosing Interval at Steady State (AUCss 0-tau)
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Time to onset of peripheral blood B cell depletion
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Duration of peripheral blood B cell depletion
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: The profile of peripheral blood NK cell changes
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Receptor occupancy of CD19 in peripheral blood
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Receptor occupancy duration of CD19 in peripheral blood
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Receptor occupancy of CD3 in peripheral blood
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Receptor occupancy duration of CD3 in peripheral blood
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: The profile of peripheral blood T-cell subset changes
timeFrame: From 1 hour before the first infusion of YK012 to the end of trial at 52 weeks
measure: Ib: Anti-Drug Antibody (ADA) positivity rate
timeFrame: From enrollment to the end of the trial at 52 weeks
measure: Ib: Neutralizing antibody (Nab) positivity rate
timeFrame: From enrollment to the end of the trial at 52 weeks
measure: Ib: Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response rates
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks
measure: BILAG-based Composite Lupus Assessment (BICLA) response rates
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in 24-hour urine protein in participants with elevated baseline proteinuria (24-hour urine protein ≥0.5 g)
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in glucocorticoid use during the study period
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in British Isles Lupus Assessment Group 2004 (BILAG-2004) score from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in Physician's Global Assessment (PGA) score from baseline
timeFrame: From the first infusion to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in 36-Item Short Form Health Survey (SF-36) score from baseline
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Change in Fatigue Severity Scale (FSS) score from baseline
timeFrame: From the first infusion of YK012 to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in IgG level from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in IgM level from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in IgA levels from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in IgE levels from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in anti-dsDNA antibody level from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in complement C3 level from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
measure: Changes in complement C4 level from baseline
timeFrame: From enrollment to the end of the trial at 52 weeks (Ib) or 76 weeks (II)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences Peking Union Medical College Hospital
state: Beijing
Study officials:
References: