A Study of Telitacicept in Patients With Primary Immunoglobulin A（IgA） Nephropathy
- Conditions
- Primary IgA Nephropathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT05799287
- Lead Sponsor
- RemeGen Co., Ltd.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 318
- Voluntary informed consent provided;
- Male or female aged ≥ 18 years old;
- IgA nephropathy confirmed by pathological biopsy;
- 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;
- eGFR ≥ 30 mL/min per 1.73 m^2 (using the CKD-EPI);
- 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.
- Clinically significant abnormal laboratory tests;
- Secondary IgA nephropathy;
- Other types of glomerular disease such as crescentic glomerulonephritis（>50%）, minimal change nephropathy with IgA deposition;
- Renal transplant;
- Cirrhosis, as assessed by the investigator;
- Experienced any of the following cardiovascular and cerebrovascular events within 24 weeks prior to randomization: myocardial infarction, unstable angina, ventricular arrhythmia, New York Heart Association（NYHA） Class II or higher heart failure, stroke, etc.;
- Sitting position SBP>140 mmHg or DBP>90 mmHg for at least once at 2 visits during the screening period;
- Poorly controlled type 1 and type 2 diabetes (glycated hemoglobin A1c[HbA1c]>8% or 64mmol/mol);
- Received immunosuppressants within 12 weeks prior to randomization, including but not limited to cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii;
- Received anti-CD20 therapy (for example, Rituximab Injection) within 24 weeks prior to randomization;
- 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;
- Hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization;
- Active tuberculosis and untreated latent tuberculosis;
- Hepatitis B: patients with active hepatitis (patients with positive HBsAg) or latent hepatitis B (patients with positive HBcAb and positive HBV-DNA);
- Hepatitis C;
- Patients with HIV;
- Malignancy within the past 5 years, except for treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, colon polyps, or cervical cancer in situ;
- Pregnant women, lactating women, and subjects with childbearing plans during the trial;
- Allergic to biological products of human origin;
- Received any investigational therapy within 4 weeks or within 5 times the half-life of the investigational product (whichever is longer) prior to randomization;
- Received live vaccination within 4 weeks prior to randomization;
- Drug or alcohol abuse/dependence within 52 weeks prior to randomization;
- Not suitable for the study in the opinion of the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telitacicept Telitacicept Subjects will be given Telitacicept 240 mg SC once a week in phase A for a total of 39 doses and once every 2 weeks in phase B for a total of 32 doses. Placebo Placebo Subjects will be given placebo SC once a week in phase A for a total of 39 doses and once every 2 weeks in phase B for a total of 32 doses.
- Primary Outcome Measures
Name Time Method Change from baseline in urine protein creatinine ratio (UPCR) 39 weeks Based on a 24-hour urine collections.
Annualized estimated glomerular filtration rate (eGFR) slope 104 weeks eGFR is calculated using the CKD-EPI formula.
- Secondary Outcome Measures
Name Time Method 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.
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 estimated glomerular filtration rate (eGFR) 39 weeks, 52 weeks,78 weeks,104 weeks eGFR is calculated using the CKD-EPI formula.
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.
Trial Locations
- Locations (101)
The First Affiliated Hospital of Bengbu Medical University
🇨🇳Bengbu, Anhui, China
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
🇨🇳Hefei, Anhui, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Wannan Medical College
🇨🇳Wuhu, Anhui, China
Beijing Anzhen Hospital Affiliated to Capital Medical University
🇨🇳Beijing, Beijing Municipality, China
Beijing Hospital
🇨🇳Beijing, Beijing Municipality, China
Beijing Tsinghua Changgung Hospital
🇨🇳Beijing, Beijing Municipality, China
Peking University First Hospital
🇨🇳Beijing, Beijing Municipality, China
Peking University People's Hospital
🇨🇳Beijing, Beijing Municipality, China
Peking University Shougang Hospital
🇨🇳Beijing, Beijing Municipality, China
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