IgAN
Conditions
Keywords
IgAN
Brief summary
This is a multicenter, randomized, double-blind, placebo controlled Phase IIb study to explore the efficacy and safety of STL303 capsules in IgAN patients. About 15 patients dignosed with primary IgAN will be enrolled and randomized to three cohorts and take different dosage of STL303 or placebo capsules orally according to protocol.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study in approximately 15 patients with primary IgA nephropathy (IgAN). Participants receiving background therapy will be randomized in a 1:1:1 ratio to receive STL303 capsules dose 1, dose 2, or placebo, administered orally once daily. The study aims to evaluate the efficacy and safety of STL303 in patients with primary IgAN and to identify the optimal clinical dose.
Interventions
DRUGSTL303
STL303 arm participants will receive a specific dose of STL303
DRUGPlacebo capsule
Placebo arm participants will receive placebo capsules
Sponsors
Sitala Bio LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients aged 18 years and older, with primary IgAN confirmed by renal biopsy: 2. eGFR (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) greater than or equal to 30 mL/min/1.73 m2 at screening and after completion of run-in. 3. UPCR greater than or equal to 0.75 g/g at screening and after completion of run-in. 4. Vaccinated against Neisseria meningitidis and Streptococcus pneumoniae before the first dose. 5. Have received stable treatment with RASis (ACEi or ARB) at the maximum recommended dose or MTD for at least 90 days prior to the first dose. 6. If the patient has been treated with SGLT2i, diuretics, other antihypertensive treatments, ERA, and/or hydroxychloroquine for IgAN prior to the first dose, the drug should also be used stably for at least 90 days.
Exclusion criteria
1. Secondary IgAN or unclear exclusion of secondary causes. 2. Rapidly progressive IgAN (eGFR decline greater than or equal to 50% in 3 months, or less than 50% but at high risk). 3. Other systemic diseases causing proteinuria/CKD or severe urinary obstruction. 4. Known or suspected immunodeficiency or hereditary complement deficiency. 5. Any organ transplant recipients except corneal. 6. Poorly controlled blood pressure (SBP greater than 150 or DBP great than 90). 7. Use of immunosuppressive drugs within 90 days or 5 half-lives. 8. Prior oral budesonide (Nefecon/Tarpeyo/Kinpeygo) within 6 months. 9. Prior complement inhibitors within 30 days, 5 half-lives, or residual effect period. 10. Major systemic diseases preventing participation (e.g., NYHA IV, severe pulmonary disease). 11. Significantly abnormal liver function (greater than 3× ULN enzymes or greater than 2× ULN bilirubin). 12. QTcF greater than 500 ms. 13. History of malignancy within 5 years (exceptions apply). 14. History of meningococcal, pneumococcal, or Hib infection. 15. Chronic/recurrent infections in past year (e.g., liver abscess, pyelonephritis). 16. Active systemic infections within 2 weeks or fever greater than 38°C within 7 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment emergent adverse events (TEAEs), adverse events (AEs) and serious adverse events (SAEs) | Adverse events will be closely monitored, and participants will report to the clinic on Days 7, 14, 30, 45, 60, 90, 135 and at end of treatment on Day 180. On Day 210 an End of study safety follow up will also be conducted. | All participants will be observed for any AE during the clinical study, including abnormalities in clinical symptoms and vital signs, physical examination, laboratory tests, and 12-lead ECG. Incidence, severity, and relationship of TEAEs and serious adverse events (SAEs) to STL303. Possible adverse events include: palpitations, nausea, vomiting, dizziness, sore throat, upper respiratory infection, loss of appetite, high temperature, chest discomfort, weakness, rash, headache, lethargy (feeling tired and low on energy) and urinary tract infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline urine protein-to-creatinine ratio (UPCR) | 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180 | Change in baseline 24-hour urine collection |
| Change in UPCR | 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60 and 90 | Change in baseline 24-hour urine collection |
| Change in urine albumin-to-creatinine ratio (UACR) | 24-hour urine collection pre-dose on Days 1 (baseline), 30, 60, 90 and 180 | Change in baseline 24-hour urine collection |
| Change in blood creatinine level | Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180 | Peripheral blood sampling |
| Change in eGFR slope | Blood sampling pre-dose on Days 1 (baseline), 14, 30, 45, 60, 90 and 180 | Peripheral blood sampling |
| Maximum Concentration at steady-state (Tmax, ss) of STL303 | Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing | Measure time to reach maximum concentration at steady-state (Tmax, ss) at steady state. |
| Maximum plasma concentration at steady-state (Cmax, ss) of STL303 | Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing | Measure maximum plasma concentration at steady-state (Cmax, ss) at steady state. |
| Trough plasma concentration at steady-state of STL303 | Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing | Measure trough plasma concentration at steady-state (Cmin, ss /Ctrough, ss), |
| Area under plasma concentration-time curve for STL303 | Pre-dose on Days 1, 7, 14, 60, 90, 135, and 180. On Day 30 pre-dose and at 1 hour (± 5 minutes), 2 hours (± 5 minutes), 4 hours (± 10 minutes), 6 hours (± 10 minutes), 8 hours (± 10 minutes), 12 hours (± 10 minutes), and 24 hours (± 1 hour) after dosing | Measure the area under the plasma concentration-time curve over one dosing interval at steady state (AUCtau) |
| Change urine protein excretion (UPE), | 24-hour urine collection pre-dose Days 1 (baseline), 30, 60, 90 and 180 | Change in baseline 24-hour urine collection |
| Alternative Pathway Activity (Wieslab Assay) | Pre-dose and post-dose on Day 1 and Day 14; pre-dose on Days 7, 60, 90, 135, and 180; intensive time points (pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours post-dose) on Day 30 | Change from baseline in complement alternative pathway (AP) functional activity as measured by the Wieslab assay in serum |
| Urinary Complement Biomarker C3a | Day 1, Day 7 (FMV only), Day 14 (FMV only), Day 30, Day 60, Day 90, Day 135 (FMV only), and Day 180 (all pre-dose) | Change from baseline in urinary levels of C3a, measured in first morning void (FMV) and 24-hour urine samples collected midstream first morning void (FMV) Urine sampling |
| Plasma Soluble Terminal Complement Complex (sC5b-9) | Day 1 through Day 180 (pre-dose at scheduled visits) | Change from baseline in plasma levels of soluble terminal complement complex (sC5b-9), a marker of terminal complement activation |
| Complement Factor B Cleavage Fragment (Bb) | Day 1 through Day 180 (pre-dose at scheduled visits) | Change from baseline in plasma levels of complement factor B cleavage fragment (Bb), a marker of alternative pathway activation |
Countries
Australia
Contacts
CONTACTClinical Operations Manager
PRINCIPAL_INVESTIGATOREugenia Pedagogos
Western Health (Sunshine Hospital)
Outcome results
None listed