Focal Segmental Glomerulosclerosis (FSGS), IgA Nephropathy (IgAN), Minimal Change Disease (MCD)
Conditions
Brief summary
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.
Interventions
DRUGEVER001
EVER001 200 mg, oral administration, twice daily (bid), for the treatment of proteinuric glomerular diseases including FSGS , MCD , and IgA
Sponsors
Everest Medicines (China) Co.,Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) | Week24 | Percentage change from baseline in 24-hour UPCR (based on 24-hour urine collection) |
| Treatment-emergent adverse events (TEAEs) | Throughout the study period, up to Week 56 | Incidence, severity, and relatedness of treatment-emergent adverse events (TEAEs) |
| Adverse events of special interest (AESIs) | Throughout the study period, up to Week 56 | Incidence of adverse events of special interest (AESIs) |
| Systolic blood pressure change from baseline | Throughout the study period, up to Week 56 | Measured in mmHg using a calibrated clinical blood pressure monitor |
| Body weight change from baseline | Throughout the study period, up to Week 56 | Measured in kilograms (kg) using a calibrated clinical scale |
| Change from baseline in clinical laboratory safety parameters | Throughout the study period, up to Week 56 | Change from baseline in routine clinical laboratory safety parameters, measured using standard validated clinical laboratory assays and reported in standard clinical units |
| Physical examination findings | Throughout the study period, up to Week 56 | Incidence of new or worsening abnormalities in physical examination findings, assessed at scheduled study visits. |
| Chest radiography findings | Throughout the study period, up to Week 56 | Incidence of new or worsening abnormalities in chest radiography findings, assessed at scheduled study visits. |
| 12-lead electrocardiogram (ECG) findings | Throughout the study period, up to Week 56 | Incidence of new or worsening abnormalities in 12-lead electrocardiogram (ECG) findings, assessed at scheduled study visits. |
| Pulse rate change from baseline | Throughout the study period, up to Week 56 | Measured in beats per minute (bpm) using a calibrated vital signs monitor |
| Diastolic blood pressure change from baseline | Throughout the study period, up to Week 56 | Measured in mmHg using a calibrated clinical blood pressure monitor |
| Body temperature change from baseline | Throughout the study period, up to Week 56 | Measured in degrees Celsius (°C) using a calibrated clinical thermometer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in 24-hour UPCR | Week 2 and thereafter, up to Week 56 | Percentage change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) |
| Proportion of participants achieving complete remission (CR) | Week 2 and thereafter, up to Week 56 | Proportion of participants achieving complete remission (CR) based on predefined criteria |
| Proportion of IgAN participants with ≥30% reduction in 24-hour UPCR from baseline | At Week 24, Week 36, and Week 52 | 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 |
| Change from baseline in estimated glomerular filtration rate (eGFR) | Week 2 and thereafter, up to Week 56 | Absolute and percentage change from baseline in estimated glomerular filtration rate (eGFR), calculated per the formula specified in the study protocol |
| eGFR slope from baseline | Baseline to Week 52 | Slope of change in estimated glomerular filtration rate (eGFR, calculated per the formula specified in the study protocol) from baseline to Week 52 |
| Percentage change from baseline in serum albumin | Week 2 and thereafter, up to Week 56 | Percentage change from baseline in serum albumin level |
| Proportion of participants achieving partial remission (PR) | Week 2 and thereafter, up to Week 56 | Proportion of participants achieving partial remission (PR) based on predefined study criteria |
| Proportion of participants achieving CR or PR | Week 2 and thereafter, up to Week 56 | Proportion of participants achieving complete remission (CR) or partial remission (PR) based on predefined study criteria |
| Time to achieve CR or PR | Baseline to Week 52 | Time from baseline to first documented complete remission (CR) or partial remission (PR), based on predefined study criteria |
| Proportion of participants with relapse (CR/PR, no rescue therapy) | From Day1 to Week 52 | Proportion of participants who experience relapse among those achieving CR or PR during the study and not receiving rescue therapy |
| Time from CR/PR to relapse | From Day1 to Week 52 | Time from first documented complete remission (CR) or partial remission (PR) to first documented relapse |
| Cumulative dose of glucocorticoids (GC) | Week 16, Week 24, Week 32, Week 40, and Week 52 | Cumulative dose of glucocorticoids (GC), measured in prednisone equivalent dose, calculated at the specified study visits |
| Proportion requiring GC increase or additional immunosuppressants | Throughout the study period (baseline to Week 56) | Proportion of participants requiring increase in GC dosage and/or initiation of additional immunosuppressants |
| Proportion of IgAN participants with positive hematuria | At baseline, Week 12, Week 24, Week 36, and Week 52 | Proportion of participants with IgAN with positive hematuria |
| Resolution of hematuria in IgAN participants | At Week 12, Week 24, Week 36, and Week 52 | Resolution of hematuria in participants with IgA |
| Change from baseline in BTK target occupancy | Throughout the study period, up to Week 56 | Change from baseline in BTK target occupancy in peripheral blood cells |
| Plasma EVER001 peak concentration (Cmax) | Throughout the study period, up to Week 56 | Plasma EVER001 peak concentration (Cmax) |
| Trough Plasma Concentration (Cmin) of EVER001 | Throughout the study period, up to Week 56 | Plasma EVER001 trough concentration (Cmin) |
| Time to Reach Peak Concentration (Tmax) of EVER00 | Throughout the study period, up to Week 56 | Time to reach peak concentration (Tmax) of EVER001 |
| Accumulation Ratio (AR) of EVER001 | Throughout the study period, up to Week 56 | Accumulation ratio (AR) of EVER001 |
Countries
China
Contacts
CONTACTEverest Clinical Trial Information Center
Outcome results
None listed