Primary Membranous Nephropathy
Conditions
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.
Interventions
DRUGEVER001
A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.
Sponsors
Everest Medicines (China) Co.,Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse events | 104 weeks. |
| clinical laboratory assessments. | 104 weeks. |
| vital signs. | 104 weeks. |
| physical examination | 104 weeks |
| ECG. | 104 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate whether EVER001 can modulate proteinuria in pMN. | 52 weeks. | Percentage change from baseline of 24 hr proteinuria throughout 52 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 the clinical response and immunological response in pMN. | 104 weeks. | To evaluate the clinical response and immunological response in pMN. |
| 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. | — |
Countries
China
Outcome results
None listed