Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001

Study Overview
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Brief Summary
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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.

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

Conditions
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Primary Membranous Nephropathy

Intervention / Treatment
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* Drug: EVER001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having clinical diagnosis of primary membranous nephropathy, as verified by biopsy. Have positive anti-PLA2R autoantibody test results > 20 relative units (RU)/ml AND < 150RU/ml at screening. During screening at least one testing of proteinuria must be >3.5 g/24h. Have nephrotic range proteinuria for at least 3 months prior to Day 1 and no improvement despite supportive therapy of ACE inhibitor or ARB unless contraindicated. Exclusion Criteria: Non-primary membranous nephropathy or other condition affecting the kidney. eGFR at screening < 60 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; immunosuppressive/immunomodulatory agents within 90 days. Acute or chronic infection. Positive serology for 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. Judged by the investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVER001<br>EVER001 for 36 weeks. | Drug: EVER001<br>* A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse event over 52 weeks. |  | 52 weeks. | 
| 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. | 
| To evaluate the clinical response and immunological response in pMN. | 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 at week 24, 36, 44, 52. | 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. |