Clinical trial NCT05967520: JMKX000189 for Moderate to Severe Active Systemic Lupus Erythematosus
Official title: A Phase IIa ,Randomized, Double-blind, Placebo-controlled, Dose-exploration Study of JMKX000189 in Treatment of Moderate to Severe Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Lead sponsor: Jemincare
Sponsor class: INDUSTRY
First posted: 2023-08-01
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The trial will evaluate pharmacodynamics，pharmacokinetics，safety，and efficacy of JMKX000189 versus placebo in participants with moderately to severely active systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment.


Eligibility criteria: Inclusion Criteria:

1. Subjects must have been diagnosed with systemic lupus erythematosus at least 24 weeks prior to screening and must be assessed to meet 2019 EULAR/ACR SLE classification criteria during screening.
2. the subject must meet one of the following at screening: a. ANA titer ≥1:80;b. anti-dsDNA antibody positive; c. Anti-Smith antibody positive.
3. At least one of the following SLE background standard therapies (including no more than one immunosuppressant) was required for 12 weeks prior to randomization, and the dose must remain stable at least 30 days until randomization and throughout study participation.

Exclusion Criteria:

1. Active lupus nephritis (defined as urinary protein \>1g/24 h or urinary total protein/creatinine ratio (UPCR) \>1 mg/mg (113 mg/mmol) within 8 weeks prior to screening or at randomization).
2. Active lupus of the central nervous system (CNS) (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, or CNS vasculitis) within 60 days prior to randomization.
3. Myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, grade III/IV heart failure, or untreated severe sleep apnea occurred ≤6 months before screening.
4. Previous or current atrioventricular block of degree Ⅱ or Ⅲ, sick sinus syndrome, symptomatic bradycardia, atrial flutter or atrial fibrillation, ventricular arrhythmia or syncope associated with heart disease, or other arrhythmia deemed clinically significant and requiring intervention or treatment.
5. A history of severe respiratory disease or interstitial pneumonia or pulmonary fibrosis，which were found by the medical history or lung function test or chest CT examination conducted during screening or within 3 months prior to screening;Or abnormal pulmonary function of medical significance: 1 second forced expiratory volume (FEV1) or forced vital capacity (FVC)\<70% of the expected value, or FEV1 /FVC \< 0.7.
6. Patients with significant abnormalities in liver, renal function and blood routine during screening, including glutamate aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 2 times the upper limit of normal value;Serum creatinine greater than 1.5 times the upper limit of normal;Hemoglobin \<90g/L;White blood cell count \<2.5×109/L, platelet count (PLT) \<75×109/L;Lymphocyte count \<0.8×109/L;Abnormal results of other laboratory tests may affect the completion of the test or interfere with the test results according to the investigator.
7. Use of cyclosporine, tacrolimus, pimelimus, and sirolimus within 1 month prior to randomization.
8. Use of thalidomide or lenalidomide within 2 months prior to randomization.
9. Rituximab, telitacicept, or leflunomide were used in the 6 months prior to randomization.
10. Use of Belliumab within 3 months prior to randomization.
11. Intravenous treatment with cyclophosphamide was received within 6 months prior to randomization or oral treatment with cyclophosphamide within 30 days prior to initial administration.
12. History of type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus with HbA1c\> 8%, or diabetic subjects with organ involvement (e.g. retinopathy or kidney disease).

Primary outcomes:
measure: Change in Total Lymphocyte Count From Baseline to Week 12
timeFrame: Baseline,Week 12
Secondary outcomes:
measure: Change from baseline to Week 4,8,12 and 16 in the modified SLEDAI (mSLEDAI) score
timeFrame: Baseline, Week 4, 8,12, and 16
measure: Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 4,8,12 and 16
timeFrame: Baseline, Week 4, 8,12, and 16
measure: Percentage of Participants Achieving No worsening in Physician Global Assessment (PGA) of Disease Activity at Week 4,8,12 and 16, No worsening defined as an increase of PGA < 0.3 Points from baseline
timeFrame: Baseline, Week 4, 8,12, and 16
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jining
country: China
facility: Jining First People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xiaofeng Zeng
role: PRINCIPAL_INVESTIGATOR
References: