Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001

Everest Medicines

Status and phase: Enrolling; Phase 1

Conditions: Primary Membranous Nephropathy

Treatments: Drug: EVER001

Study type: Interventional

Funder types: Industry

Identifiers

NCT05800873

ES108001

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

EVER001 100mg

Experimental group

Description:

EVER001 100mg QD for 4 weeks, followed by EVER001 100mg BID for 32 weeks.

Treatment:

Drug: EVER001

Drug: EVER001

EVER001 200mg

Experimental group

Description:

EVER001 200mg BID for 36 weeks.

Treatment:

Drug: EVER001

Drug: EVER001