Clinical trial NCT05800873: Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001
Official title: A Phase 1b/2 Study To Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001 In Participants With Selected Proteinuric Glomerular Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Primary Membranous Nephropathy
Lead sponsor: Everest Medicines (China) Co.,Ltd.
Sponsor class: INDUSTRY
First posted: 2023-04-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 disease is primary membranous nephropathy.


Eligibility criteria: 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.

Primary outcomes:
measure: adverse events
timeFrame: 104 weeks.
measure: clinical laboratory assessments.
timeFrame: 104 weeks.
measure: vital signs.
timeFrame: 104 weeks.
measure: physical examination
timeFrame: 104 weeks
measure: ECG.
timeFrame: 104 weeks.
Secondary outcomes:
measure: To evaluate whether EVER001 can modulate proteinuria in pMN.
timeFrame: 52 weeks.
measure: To evaluate whether EVER001 can modulate anti-PLA2R autoantibodies in patients with positive baseline levels of these antibodies.
timeFrame: 52 weeks.
measure: To evaluate the clinical response and immunological response in pMN.
timeFrame: 104 weeks.
measure: Maximum Observed Plasma Concentration (Cmax) of EVER001
timeFrame: 52 weeks.
measure: Minimum Observed Plasma Concentration (Cmin) of EVER001
timeFrame: 52 weeks.
measure: Time to Reach Maximum Observed Concentration (Tmax) of EVER001.
timeFrame: 52 weeks.
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
state: Changsha
city: Chongqing
country: China
facility: The First Affiliated Hospital of PLA Army Medical University
state: Chongqing
city: Guangzhou
country: China
facility: The Third Affiliated Hospital,Sun Yat Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Harbin
city: Changsha
country: China
facility: Xiangya Third Hospital, Central South University
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
state: Inner Mongolia Autonomous Region
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Xian
country: China
facility: The First Affiliated Hospital of Medical college of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Province People's Hospital
state: Sichuan
city: Shanxi
country: China
facility: Second Hospital of Shanxi Medical University
state: Taiyuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: The first affliated hospital of NingBo university
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
References: