YK012 for moderate-to-severe lupus (SLE)

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

This study will test YK012 in adults with moderate-to-severe lupus to see if it is safe and can lower disease activity.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 189 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Excyte Biopharma Ltd (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07010835 on ClinicalTrials.gov

What this trial studies

This is a Phase Ib/II interventional trial of YK012 in adults with moderate-to-severe systemic lupus erythematosus (SLE). Phase Ib includes a dose-escalation stage to establish safety and tolerability followed by a dose-expansion stage to further evaluate safety, tolerability, and preliminary effectiveness in reducing disease activity. Phase II is designed to measure efficacy of the selected dose(s) for reducing disease activity compared with baseline while also collecting pharmacokinetic, pharmacodynamic, and immunogenicity data. Participants must have confirmed SLE with moderate-to-high activity and be on stable background therapy during the trial.

Who should consider this trial

Good fit: Adults aged 18–75 with a confirmed SLE diagnosis for at least 24 weeks, positive lupus autoantibodies, a SLEDAI-2K score of 7 or higher, and stable background therapy are the intended participants.

Not a fit: People with only mild SLE, those with known allergy to monoclonal antibodies or immunoglobulins, or those who do not meet the activity or laboratory criteria are unlikely to benefit from joining this study.

Why it matters

Potential benefit: If successful, YK012 could provide a new biologic option that reduces lupus disease activity and improves symptoms for people with moderate-to-severe SLE.

How similar studies have performed: Other monoclonal antibody therapies for SLE (for example, belimumab and anifrolumab) have shown clinical benefit in some patients, so this approach builds on prior successes though responses have varied across agents and subgroups.

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.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xiaofeng Zeng, Doctor of Medicine

Conditions Systemic Lupus Erythematosus