Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001

A Phase 1b/2 Study To Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001 In Participants With Selected Proteinuric Glomerular Diseases

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 disease is primary membranous nephropathy.

Study Overview

• Status: Recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: EVER001

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lixia Wang; Phone Number: 00862180123250; Email: lixia.wang@everestmedicines.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University First Hospital
    • Contact: Minghui Zhao
  • Changsha
    • Changsha, Changsha, China
      • Recruiting
      • The second Xiangya hospital of central south university
      • Contact: Liu Hong
  • Chongqing
    • Chongqing, Chongqing, China
      • Recruiting
      • The First Affiliated Hospital of PLA Army Medical University
      • Contact: Zhao Hong Wen
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The Third Affiliated Hospital,Sun Yat Sen University
      • Contact: Peng Hui
    • Shenzhen, Guangdong, China
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Xiong Zu Ying
  • Harbin
    • Harbin, Harbin, China
      • Recruiting
      • The Second Affiliated Hospital of Harbin Medical University
      • Contact: Du Xuan Yi
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Xiangya Third Hospital, Central South University
      • Contact: Zhang Hao
  • Inner Mongolia Autonomous Region
    • Baotou, Inner Mongolia Autonomous Region, China
      • Recruiting
      • The First Affiliated Hospital of Baotou Medical College
      • Contact: Wang Cai Li
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhongda Hospital Southeast University
      • Contact: Liu Bi Cheng
    • Suzhou, Jiangsu, China
      • Recruiting
      • The Second Affiliated Hospital of Soochow University
      • Contact: Zeng Ying
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Xu Cheng Yun
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Zhang Wen
  • Shanxi
    • Xian, Shanxi, China
      • Recruiting
      • The First Affiliated Hospital of Medical college of Xi'an Jiaotong University
      • Contact: Lu Wan Hong
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan Province People's Hospital
      • Contact: Chen Xiu Ling
  • Taiyuan
    • Shanxi, Taiyuan, China
      • Recruiting
      • Second Hospital of Shanxi Medical University
      • Contact: Wang Li Hua
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Ma Kun Ling
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Li Yi Wen
    • Ningbo, Zhejiang, China
      • Recruiting
      • The first affliated hospital of NingBo university
      • Contact: Huang Jian Cheng
    • Taizhou, Zhejiang, China
      • Recruiting
      • Taizhou Hospital of Zhejiang Province
      • Contact: Xu Guang Biao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Having clinical diagnosis of primary membranous nephropathy, as verified by biopsy.
2. Have positive anti-PLA2R autoantibody test results > 20 relative units (RU)/ml.
3. During screening at least one testing of proteinuria must be >3.5 g/24h.
4. 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.

Exclusion Criteria:

1. Non-primary membranous nephropathy or other condition affecting the kidney.
2. eGFR at screening < 45 mL/min/1.73m2 or kidney function not stable .
3. Uncontrolled hypertension .
4. Serum albumin level at screening # 25g/l.
5. 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.
6. Acute or chronic infection,including positivity of tuberculosis infection test.
7. Positive serology for TP,HIV, HBV, or HCV.
8. 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.
9. Judged by the investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVER001 100mg; EVER001 100mg QD for 4 weeks, followed by EVER001 100mg BID for 32 weeks.	Drug: EVER001; A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.
Experimental: EVER001 200mg; EVER001 200mg BID for 36 weeks.	Drug: EVER001; A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
adverse events	104 weeks.
clinical laboratory assessments.	104 weeks.
vital signs.	104 weeks.
physical examination	104 weeks
ECG.	104 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate whether EVER001 can modulate proteinuria in pMN.	Percentage change from baseline of 24 hr proteinuria throughout 52 weeks.	52 weeks.
To evaluate whether EVER001 can modulate anti-PLA2R autoantibodies in patients with positive baseline levels of these antibodies.	Percentage change from baseline of anti-PLA2R autoantibody level throughout 52 weeks.	52 weeks.
Maximum Observed Plasma Concentration (Cmax) of EVER001		52 weeks.
Minimum Observed Plasma Concentration (Cmin) of EVER001		52 weeks.
Time to Reach Maximum Observed Concentration (Tmax) of EVER001.		52 weeks.
To evaluate the clinical response and immunological response in pMN.	To evaluate the clinical response and immunological response in pMN.	104 weeks.

Collaborators and Investigators

• Sponsor: Everest Medicines (China) Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, Membranous
• Other Study ID Numbers: ES108001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No