Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EVER001 in Participants With Selected Proteinuric Glomerular Diseases

Phase 2RecruitingNCT07614477

Everest Medicines (China) Co.,Ltd.45 enrolled

Overview

This is a Phase 1b/2, open-label, multi-center study evaluating the therapeutic potential and safety of the investigational drug EVER001 in adults with FSGS, MCD, or IgAN. EVER001 acts on multiple immune pathways without directly affecting T cells or depleting B cells (both are lymphocytes). The study will be conducted at \~30 centers in China, enrolling 45 participants aged 18-75 years (15 per indication). The IMP is a 100 mg oral capsule, dosed at 200 mg twice daily (2 capsules per dose, 4 daily) for 52 weeks.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Minimal Change Disease (MCD)IgA Nephropathy (IgAN)Focal Segmental Glomerulosclerosis (FSGS)

Interventions

EVER001 200 mg, oral administration, twice daily (bid), for the treatment of proteinuric glomerular diseases including FSGS , MCD , and IgA

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Primary FSGS or MCD/IgAN confirmed by renal biopsy * eGFR ≥ 45 mL/min/1.73 m² * For participants with FSGS or MCD: must have a 24-hour urine protein-to-creatinine ratio (UPCR) \> 3.5 g/g and serum albumin \< 30 g/L during the screening period * For participants in the IgAN group: 24-hour UPCR ≥ 0.8 g/g; ARB or ACEI stable for ≥ 12 weeks prior to Day 1 * Patients with FSGS or MCD who have not been treated with immunosuppressants or are sensitive to prior immunosuppressant treatment Exclusion Criteria: * Hereditary or secondary FSGS/MCD; collapsing FSGS * BMI ≥ 35 kg/m² in participants with FSGS/MCD * Evidence of diabetes mellitus or a history of diabetes mellitus * Acute or chronic infection requiring treatment * Patients infected with HIV, hepatitis C, syphilis, or hepatitis B * Patients with current or prior inadequately treated active tuberculosis (TB), latent TB, or evidence of current household contact with active TB * At risk of bleeding * Baseline 24-hour UPCR \> 3 g/g and serum albumin \< 30 g/L in participants with IgAN

Locations (2)

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

Tianjin Medical University General Hospital

Tianjin, Hebei, China

RECRUITING

Outcomes

Primary Outcomes

Percentage change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR)

Percentage change from baseline in 24-hour UPCR (based on 24-hour urine collection)

Time frame: Week24

Treatment-emergent adverse events (TEAEs)

Incidence, severity, and relatedness of treatment-emergent adverse events (TEAEs)

Time frame: Throughout the study period, up to Week 56

Adverse events of special interest (AESIs)

Incidence of adverse events of special interest (AESIs)

Time frame: Throughout the study period, up to Week 56

Systolic blood pressure change from baseline

Measured in mmHg using a calibrated clinical blood pressure monitor

Time frame: Throughout the study period, up to Week 56

Body weight change from baseline

Measured in kilograms (kg) using a calibrated clinical scale

Time frame: Throughout the study period, up to Week 56

Change from baseline in clinical laboratory safety parameters

Change from baseline in routine clinical laboratory safety parameters, measured using standard validated clinical laboratory assays and reported in standard clinical units

Time frame: Throughout the study period, up to Week 56

Physical examination findings

Incidence of new or worsening abnormalities in physical examination findings, assessed at scheduled study visits.

Time frame: Throughout the study period, up to Week 56

Chest radiography findings

Incidence of new or worsening abnormalities in chest radiography findings, assessed at scheduled study visits.

Time frame: Throughout the study period, up to Week 56

12-lead electrocardiogram (ECG) findings

Incidence of new or worsening abnormalities in 12-lead electrocardiogram (ECG) findings, assessed at scheduled study visits.

Time frame: Throughout the study period, up to Week 56

Pulse rate change from baseline

Measured in beats per minute (bpm) using a calibrated vital signs monitor

Time frame: Throughout the study period, up to Week 56

Diastolic blood pressure change from baseline

Measured in mmHg using a calibrated clinical blood pressure monitor

Time frame: Throughout the study period, up to Week 56

Body temperature change from baseline

Measured in degrees Celsius (°C) using a calibrated clinical thermometer

Time frame: Throughout the study period, up to Week 56

Secondary Outcomes

Percentage change from baseline in 24-hour UPCR

Percentage change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR)

Time frame: Week 2 and thereafter, up to Week 56

Proportion of participants achieving complete remission (CR)

Proportion of participants achieving complete remission (CR) based on predefined criteria

Time frame: Week 2 and thereafter, up to Week 56

Proportion of IgAN participants with ≥30% reduction in 24-hour UPCR from baseline

Proportion of participants with IgAN achieving ≥30% reduction in 24-hour urine protein-to-creatinine ratio (UPCR) from baseline, assessed at Week 24, Week 36, and Week 52

Time frame: At Week 24, Week 36, and Week 52

Change from baseline in estimated glomerular filtration rate (eGFR)

Absolute and percentage change from baseline in estimated glomerular filtration rate (eGFR), calculated per the formula specified in the study protocol

Time frame: Week 2 and thereafter, up to Week 56

eGFR slope from baseline

Slope of change in estimated glomerular filtration rate (eGFR, calculated per the formula specified in the study protocol) from baseline to Week 52

Time frame: Baseline to Week 52

Percentage change from baseline in serum albumin

Percentage change from baseline in serum albumin level

Time frame: Week 2 and thereafter, up to Week 56

Proportion of participants achieving partial remission (PR)

Proportion of participants achieving partial remission (PR) based on predefined study criteria

Time frame: Week 2 and thereafter, up to Week 56

Proportion of participants achieving CR or PR

Central Contacts

Everest Clinical Trial Information Center

CONTACT

+86 21 8012 5712 ctinfo.center@everestmedicines.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Proportion of participants achieving complete remission (CR) or partial remission (PR) based on predefined study criteria

Time frame: Week 2 and thereafter, up to Week 56

Time to achieve CR or PR

Time from baseline to first documented complete remission (CR) or partial remission (PR), based on predefined study criteria

Time frame: Baseline to Week 52

Proportion of participants with relapse (CR/PR, no rescue therapy)

Proportion of participants who experience relapse among those achieving CR or PR during the study and not receiving rescue therapy

Time frame: From Day1 to Week 52

Time from CR/PR to relapse

Time from first documented complete remission (CR) or partial remission (PR) to first documented relapse

Time frame: From Day1 to Week 52

Cumulative dose of glucocorticoids (GC)

Cumulative dose of glucocorticoids (GC), measured in prednisone equivalent dose, calculated at the specified study visits

Time frame: Week 16, Week 24, Week 32, Week 40, and Week 52

Proportion requiring GC increase or additional immunosuppressants

Proportion of participants requiring increase in GC dosage and/or initiation of additional immunosuppressants

Time frame: Throughout the study period (baseline to Week 56)

Proportion of IgAN participants with positive hematuria

Proportion of participants with IgAN with positive hematuria

Time frame: At baseline, Week 12, Week 24, Week 36, and Week 52

Resolution of hematuria in IgAN participants

Resolution of hematuria in participants with IgA

Time frame: At Week 12, Week 24, Week 36, and Week 52

Change from baseline in BTK target occupancy

Change from baseline in BTK target occupancy in peripheral blood cells

Time frame: Throughout the study period, up to Week 56

Plasma EVER001 peak concentration (Cmax)

Time frame: Throughout the study period, up to Week 56

Trough Plasma Concentration (Cmin) of EVER001

Plasma EVER001 trough concentration (Cmin)

Time frame: Throughout the study period, up to Week 56

Time to Reach Peak Concentration (Tmax) of EVER00

Time to reach peak concentration (Tmax) of EVER001

Time frame: Throughout the study period, up to Week 56

Accumulation Ratio (AR) of EVER001

Accumulation ratio (AR) of EVER001

Time frame: Throughout the study period, up to Week 56