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Evaluate The Efficacy, Safety, Pharmacokinetics And Pharmacodynamics Of EVER001

Primary Purpose

Primary Membranous Nephropathy

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
EVER001
Sponsored by
Everest Medicines (China) Co.,Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Membranous Nephropathy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    EVER001

    Arm Description

    EVER001 for 36 weeks.

    Outcomes

    Primary Outcome Measures

    Incidence of adverse event over 52 weeks.
    To evaluate whether EVER001 can modulate proteinuria in pMN.
    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.
    Percentage change from baseline of anti-PLA2R autoantibody level throughout 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.
    Maximum Observed Plasma Concentration (Cmax) of EVER001
    Minimum Observed Plasma Concentration (Cmin) of EVER001
    Time to Reach Maximum Observed Concentration (Tmax) of EVER001.

    Secondary Outcome Measures

    Full Information

    First Posted
    March 9, 2023
    Last Updated
    March 23, 2023
    Sponsor
    Everest Medicines (China) Co.,Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05800873
    Brief Title
    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

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 15, 2023 (Anticipated)
    Primary Completion Date
    January 15, 2026 (Anticipated)
    Study Completion Date
    April 15, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Everest Medicines (China) Co.,Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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 is primary membranous nephropathy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Membranous Nephropathy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    EVER001
    Arm Type
    Experimental
    Arm Description
    EVER001 for 36 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    EVER001
    Intervention Description
    A highly selective, oral, reversable, covalent Bruton tyrosine kinase (BTK) inhibitor with high selectivity over other kinases.
    Primary Outcome Measure Information:
    Title
    Incidence of adverse event over 52 weeks.
    Time Frame
    52 weeks.
    Title
    To evaluate whether EVER001 can modulate proteinuria in pMN.
    Description
    Percentage change from baseline of 24 hr proteinuria throughout 52 weeks.
    Time Frame
    52 weeks.
    Title
    To evaluate whether EVER001 can modulate anti-PLA2R autoantibodies in patients with positive baseline levels of these antibodies.
    Description
    Percentage change from baseline of anti-PLA2R autoantibody level throughout 52 weeks.
    Time Frame
    52 weeks.
    Title
    To evaluate the clinical response and immunological response in pMN.
    Description
    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.
    Time Frame
    52 weeks.
    Title
    Maximum Observed Plasma Concentration (Cmax) of EVER001
    Time Frame
    52 weeks.
    Title
    Minimum Observed Plasma Concentration (Cmin) of EVER001
    Time Frame
    52 weeks.
    Title
    Time to Reach Maximum Observed Concentration (Tmax) of EVER001.
    Time Frame
    52 weeks.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Lixia Wang
    Phone
    00862180123250
    Email
    lixia.wang@everestmedicines.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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