Primary IgA Nephropathy
Conditions
Keywords
Autoimmune Diseases, Immune System Diseases, IgA Nephropathy
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Telitacicept in patients with primary IgA nephropathy at risk of progressing to end-stage renal disease(ESRD), despite maximum tolerated treatment with renin-angiotensin system(RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).
Detailed description
This study consists of a 5-week screening period, a double-blind treatment period divided into phase A and phase B. Eligible subjects will be randomly assigned in a 1:1 ratio to receive either Telitacicept 240mg or placebo. Subjects will be given subcutaneous injection（SC） Telitacicept or placebo once a week for a total of 39 doses in phase A and once every 2 weeks for a total of 32 doses in phase B. Primary endpoint of phase A will be measured at week 39. Primary endpoint of phase B will be measured at week 104.
Interventions
BIOLOGICALTelitacicept
Subcutaneous injection
DRUGPlacebo
Placebo to Telitacicept
Sponsors
RemeGen 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. Voluntary informed consent provided; 2. Male or female aged ≥ 18 years old; 3. IgA nephropathy confirmed by pathological biopsy; 4. During the screening period, UPCR ≥ 0.8 g/g or 24-hour urine protein ≥ 1.0 g/day based on 24-hour urine collection at Visit 1 and/or Visit 2 and at Visit 3; 5. eGFR ≥ 30 mL/min per 1.73 m\^2 (using the CKD-EPI); 6. Have been on a treatment regimen including ACEI/ARB for 12 weeks and on a stable use of ACEI/ARB medication at the maximum tolerated dose/maximum allowable dose within 4 weeks prior to randomization. Subjects who use both ACEIs and ARBs will be excluded.
Exclusion criteria
1. Subjects with abnormal laboratory tests, including but not limited to the following: 1. White blood cell count \< 1.5×109/L 2. Neutrophils \< 1.0×109/L 3. Hemoglobin \< 85.0 g/L 4. Platelet count \< 80.0×109/L 5. Total bilirubin \>2×ULN 6. ALT\>3×ULN 7. AST\>3×ULN 8. Alkaline phosphatase\>2×ULN 9. Creatine kinase\>5×ULN 10. IgA\<10 mg/dL; or IgG≤400mg/dL； 2. Patients with secondary IgA nephropathy, including but not limited to: Henoch-Schonlein purpura, ankylosing spondylitis, systemic lupus erythematosus, etc.; 3. Patients with other types of glomerular disease such as crescentic glomerulonephritis, minimal change nephropathy with IgA deposition;; 4. Renal transplant; 5. Patients with cirrhosis, as assessed by the investigator; 6. Patients who experienced any of the following cardiovascular and cerebrovascular events within 24 weeks prior to randomization: myocardial infarction, unstable angina, ventricular arrhythmia, NYHA Class II or higher heart failure, stroke, etc.; 7. Sitting position SBP\>140 mmHg or DBP\>90 mmHg for at least once at 2 visits during the screening period; 8. Patients with poorly controlled type 1 and type 2 diabetes (glycated hemoglobin A1c\[HbA1c\] \> 8% or 64mmol/mol); 9. Treatment with immunosuppressants within 12 weeks prior to randomization, including but not limited to cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii; 10. Treatment with anti-CD20 therapy (for example, Rituximb Injection) within 24 weeks prior to randomization; 11. Received systemic glucocorticoid treatment within 12 weeks prior to randomization, excluding the followings: ① received systemic treatment with prednisolone ≤ 0.5mg/kg or equivalent glucocorticoid for non- IgA nephropathy for no more than 3 courses (≤ 2 weeks per course) in the past 52 weeks; ② topical administration or nasal inhalation; 12. Had hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization; 13. Patients with active tuberculosis; 14. Hepatitis B: patients with active or latent hepatitis B (potive HBcAb and HBV-DNA); According to the test results of hepatitis B five items, subjects with positive HBsAg will be excluded; subjects who are HBsAg-negative but HBcAb-positive, whether HBsAb is positive or negative, should be tested for HBV-DNA: if HBV-DNA is positive, patients should be excluded; if HBV-DNA is negative, patients can participate in the trial, and subjects are advised to take oral entecavir for prophylactic antiviral therapy during the trial; 15. Patients with hepatitis C; 16. Patients with HIV infection; 17. Patients with malignancy within the past 5 years, except for treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, colon polyps, or cervical cancer in situ; 18. Pregnant women, lactating women, and subjects with childbearing plans during the trial; 19. Allergic to biological products of human origin; 20. Participated in any clinical trial within 4 weeks or within 5 times the half-life of the investigational drug participating (whichever is longer) prior to randomization; 21. Received live vaccination within 4 weeks prior to randomization; 22. Drug or alcohol abuse/dependence within 52 weeks prior to randomization; 23. Other circumstances that, in the opinion of the investigator, are not suitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized estimated glomerular filtration rate (eGFR) slope | 104 weeks | eGFR is calculated using the CKD-EPI formula. |
| Change from baseline in urine protein creatinine ratio (UPCR) | 39 weeks | Based on a 24-hour urine collections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 30% reduction from baseline in eGFR | up to 104 weeks | eGFR is calculated using the CKD-EPI formula and confirmed by a second sample collection and calculation after at least 4 weeks. |
| Proportion of patients with a 40% decrease in estimated glomerular filtration rate (eGFR) compared with baseline | up to 104 weeks | eGFR is calculated using the CKD-EPI formula and confirmed by a second sample collection and calculation after at least 4 weeks. |
| Proportion of patients received rescue treatment. | up to 104 weeks | patients using systemic immunosuppressive medications, glucocorticoids (GCSs), etc. |
| Incidence and severity of adverse events | up to 104 weeks | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. |
| Change from baseline in urine protein creatinine ratio (UPCR) | 52 weeks,78 weeks,104 weeks | Based on 24-hour urine collections. |
| Change from baseline in UACR in urine albumin-to-creatinine ratio (UACR) | 39 weeks, 52 weeks,78 weeks,104 weeks | Based on 24-hour urine collections. |
| Time to composite endpoint event | up to 104 weeks | The composite endpoint event is defined as initiation of maintenance renal dialysis (for at least 1 month), eGFR \<15 mL/min/1.73 m\^2, renal transplant, or death due to renal failure. eGFR is calculated using the CKD-EPI formula (CKD-EPI). |
| Proportion of patients achieving urine protein creatinine ratio (UPCR) < 0.8 g/g | 39 weeks, 52 weeks,78 weeks,104 weeks | UPCR is calculated based on 24-hour urine collections; |
| Annualized estimated glomerular filtration rate (eGFR) slope | 52 weeks | eGFR is calculated using the CKD-EPI formula. |
| Change from baseline in estimated glomerular filtration rate (eGFR) | 39 weeks, 52 weeks,78 weeks,104 weeks | eGFR is calculated using the CKD-EPI formula. |
| Proportion of patients with a 30% decrease in estimated glomerular filtration rate (eGFR) compared with baseline | 39 weeks | eGFR is calculated using the CKD-EPI formula. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 24-hour urine protein | 39 weeks | based on 24-hour urine collections |
Countries
China
Outcome results
None listed