Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001

Primary Membranous Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05800873
• Other study ID #: ES108001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 15, 2023
• Est. completion date: April 15, 2026

Study information

• Verified date: January 2024
• Source: Everest Medicines (China) Co.,Ltd.
• Contact: Lixia Wang
• Phone: 00862180123250
• Email: lixia.wang[@]everestmedicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 is primary membranous nephropathy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 15, 2026
• Est. primary completion date: January 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 despite supportive therapy of ACE inhibitor or ARB unless contraindicated, for patients who have two tests of proteinuria=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.

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Primary Membranous Nephropathy

Intervention

Drug:
• EVER001
A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Everest Medicines (China) Co.,Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse event over 52 weeks.		52 weeks.
Primary	To evaluate whether EVER001 can modulate proteinuria in pMN.	Percentage change from baseline of 24 hr proteinuria throughout 52 weeks.	52 weeks.
Primary	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.
Primary	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, 28(chort1),36, 44, 52.	52 weeks.
Primary	Maximum Observed Plasma Concentration (Cmax) of EVER001		52 weeks.
Primary	Minimum Observed Plasma Concentration (Cmin) of EVER001		52 weeks.
Primary	Time to Reach Maximum Observed Concentration (Tmax) of EVER001.		52 weeks.