IgAN
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo controlled Phase IIb study to explore the efficacy and safety of FXS6837 capsules in IgAN patients. About 60 patients dignosed with primary IgAN will be enrolled and randomized to three cohorts and take different dosage of FXS6837 or placebo capsules orally according to protocol.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study in approximately 60 patients with primary IgA nephropathy (IgAN). Participants receiving background therapy will be randomized in a 1:1:1 ratio to receive FXS6837 capsules dose 1,dose 2, or placebo, administered orally once daily. The study aims to evaluate the efficacy and safety of FXS6837 in patients with primary IgAN and to identify the optimal clinical dose.
Interventions
DRUGFXS6837 Dose 1
FXS6837 taken orally once a day
DRUGFXS6837 Dose 2
FXS6837 taken orally once a day
DRUGPlacebo Capsule
Placebo taken orally once a day
Sponsors
Shanghai Fosun Pharmaceutical Industrial Development Co. 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. Adult male or female patients aged ≥18 years with biopsy-confirmed primary IgA nephropathy (IgAN), meeting all of the following: 1. A qualifying renal biopsy performed within the past 8 years; 2. ≤50% tubulointerstitial fibrosis; 3. Crescent formation present in ≤50% of glomeruli; 4. If a historical biopsy is not available, a biopsy may be performed during screening. 2. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² at screening and at the end of the run-in period. 3. Urine protein-to-creatinine ratio (UPCR) ≥0.75 g/g at screening and at the end of the run-in period. 4. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae is required prior to initiation of study treatment. If not previously vaccinated or if a booster is required, 5. vaccination should be administered according to local regulations at least 2 weeks prior to first dose. If treatment must begin earlier, prophylactic antibiotic therapy should be initiated. 5. Patients must have received a stable dose of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), at the locally approved maximum daily dose or maximally tolerated dose (per investigator judgment), for at least 90 days prior to first dose. If receiving sodium-glucose cotransporter-2 inhibitors (SGLT2i), endothelin receptor antagonists (ERA), or hydroxychloroquine, doses must also be stable for at least 90 days prior to first dose (per investigator judgment).
Exclusion criteria
1. Secondary IgA nephropathy (IgAN), as defined by the investigator. 2. Rapidly progressive IgAN, defined as ≥50% decline in eGFR (CKD-EPI) within 3 months, or \<50% decline but considered by the investigator to be at risk of rapid renal function deterioration. 3. Other systemic diseases associated with proteinuria or chronic kidney disease (e.g., diabetic nephropathy, lupus nephritis, ANCA-associated vasculitis), or severe urinary tract obstruction or dysuria. 4. Prior treatment with immunosuppressive agents, including but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF), mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids within 90 days (or 5 half-lives, whichever is longer) prior to first dose. 5. Prior treatment with oral budesonide (Nefecon®) within 6 months prior to first dose. 6. Prior treatment with other complement inhibitors within 30 days (or 5 half-lives, whichever is longer) prior to first dose. 7. Positive test results for HIV; active syphilis infection; chronic hepatitis B infection (HBsAg positive with HBV DNA \> lower limit of quantification \[LOQ\]); or hepatitis C infection (positive HCV antibody with detectable HCV RNA). 8. Active tuberculosis at screening. 9. Clinically significant abnormal liver function at screening, defined as any of the following: ALT, AST, GGT, or ALP \>3 × upper limit of normal (ULN), or total bilirubin \>2 × ULN. 10. History of meningococcal infection. 11. Active systemic bacterial, viral (including COVID-19), or fungal infection within 14 days prior to first dose, or body temperature \>38°C within 7 days prior to first dose.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at Day180 | baseline and Day180 |
Secondary
| Measure | Time frame |
|---|---|
| Ratio to baseline in Urine Protein to Creatinine Ratio at Day90 | baseline and Day90 |
| Ratio to baseline in Urine Protein to Creatinine Ratio | up to Day180 |
| Ratio to baseline in Urine Albumin to Creatinine Ratio | up to Day180 |
| Ratio to baseline in Urinary protein excretion（UPE） | up to Day180 |
| Ratio to baseline in Urinary Albumin excretion（UAE） | up to Day180 |
| Change from baseline of serum creatinine | up to Day180 |
| Change from baseline of estimated glomerular filtration rate（eGFR） | up to Day180 |
Countries
China
Contacts
CONTACTJicheng LV, Doctor
CONTACTYang Li, Doctor
PRINCIPAL_INVESTIGATORJicheng Lv, Doctor
Peking University First Hospital
Outcome results
None listed