Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001
- Registration Number
- NCT05800873
- Lead Sponsor
- Everest Medicines (China) Co.,Ltd.
- Brief Summary
EVER001 is a highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases, which is being developed to treat proteinuric glomerular diseases.
The overall aim of the study is to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of EVER001 in subjects with selected proteinuric glomerular diseases. The first targeted is primary membranous nephropathy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Having clinical diagnosis of primary membranous nephropathy, as verified by biopsy.
- Have positive anti-PLA2R autoantibody test results > 20 relative units (RU)/ml.
- During screening at least one testing of proteinuria must be >3.5 g/24h.
- Have nephrotic range proteinuria for at least 8 weeks prior to Day 1 and no improvement (<50% reduction) despite supportive therapy of ACE inhibitor or ARB unless contraindicated, for patients who have two tests of proteinuria during screening ≥8.0g/24h, the duration of nephrotic range proteinuria for at least 8 weeks is not required.
- Non-primary membranous nephropathy or other condition affecting the kidney.
- eGFR at screening < 45 mL/min/1.73m2 or kidney function not stable .
- Uncontrolled hypertension .
- Serum albumin level at screening # 25g/l.
- Have received: B-cell targeted therapy except rituximab at any time;Rituximab and the biosimilars within 2 years (participants with rituximab treatment between 1 and 2 years prior to Day 1 are eligible if there is documented evidence of B-cell repopulation to >90% of Lower Limits of Normal Range.); Cyclophosphamide or Chlorambucil within 180 days;other immunosuppressive/immunomodulatory agents within 90 days;greater than 30mg/day prednisone or equivalence within 30 days.
- Acute or chronic infection,including positivity of tuberculosis infection test.
- Positive serology for TP,HIV, HBV, or HCV.
- Lab testing abnormality as: WBC< 3000/mm³, Lymphocyte < 1000/ mm³, neutrophil <1500/mm³, Hb < 80g/L, Platelet count <100×10e9/ L, Prothrombin time>1.5×ULN, Activated partial thromboplastin time ≥1.5×ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 1.5×ULN, alkaline phosphatase and bilirubin >1.5×ULN.
- Judged by the investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EVER001 100mg EVER001 EVER001 100mg QD for 4 weeks, followed by EVER001 100mg BID for 32 weeks. EVER001 200mg EVER001 EVER001 200mg BID for 36 weeks.
- Primary Outcome Measures
Name Time Method Safety and tolerability Safety and tolerability as assessed by evaluation of adverse events, clinical laboratory assessments, vital signs, PE, and ECG. 104 weeks. To evaluate whether EVER001 can modulate anti-PLA2R autoantibodies in patients with positive baseline levels of these antibodies. 52 weeks. Percentage change from baseline of anti-PLA2R autoantibody level throughout 52 weeks.
To evaluate whether EVER001 can modulate proteinuria in pMN. 52 weeks. Percentage change from baseline of 24 hr proteinuria throughout 52 weeks.
To evaluate the clinical response and immunological response in pMN. 104 weeks. Percentage change from baseline of UPCR; Percentage change from baseline of eGFR; Change from baseline in serum creatinine levels; Change from baseline in serum albumin levels; Incidence of complete or partial remission (complete remission: proteinuria \< 0.3g/24h; partial remission: proteinuria \< 3.5g/24h but ≥ 0.3g/24h AND decrease of \>50% regardless of eGFR or the serum albumin level from baseline); Incidence of anti-PLA2R autoantibody remission (Full response: antibody titre \< 20 relative units (RU)/ml (negative); Partial response: reduction in antibody titre ≥ 50%; Relapse rate; Treatment failure.
To assess the pharmacokinetics (PK) of EVER001 in patients with pMN Maximum Observed Plasma Concentration (Cmax) of EVER001, Minimum Observed Plasma Concentration (Cmin) of EVER001, Time to Reach Maximum Observed Concentration (Tmax) of EVER001. 52 weeks.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
The Second Xiangya Hospital Of Central South University
🇨🇳Changsha, Changsha, China
The First Affiliated Hospital of PLA Army Medical University
🇨🇳Chongqing, Chongqing, China
The Third Affiliated Hospital,Sun Yat Sen University
🇨🇳Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Harbin, China
Xiangya Third Hospital, Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Baotou Medical College
🇨🇳Baotou, Inner Mongolia Autonomous Region, China
Zhongda Hospital Southeast University
🇨🇳Nanjing, Jiangsu, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Medical college of Xi'an Jiaotong University
🇨🇳Xian, Shanxi, China
Sichuan Province People's Hospital
🇨🇳Chengdu, Sichuan, China
Second Hospital of Shanxi Medical University
🇨🇳Shanxi, Taiyuan, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
The first affliated hospital of NingBo university
🇨🇳Ningbo, Zhejiang, China
Taizhou Hospital of Zhejiang Province
🇨🇳Taizhou, Zhejiang, China
Peking University First Hospital
🇨🇳Beijing, China