A Study of Telitacicept in Patients With Primary IgA Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Telitacicept in patients with primary IgA nephropathy.

Detailed Description
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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 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.

Official Title
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A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Telitacicept in Patients With IgA Nephropathy

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Biological: Telitacicept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary informed consent provided; Male or female aged ≥ 18 years old; IgA nephropathy confirmed by pathological biopsy; During the screening period, UPCR ≥ 0.5 g/g 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. Exclusion Criteria: Subjects with clinically significant abnormal laboratory tests; Patients with secondary IgA nephropathy; Patients with other types of glomerular disease such as crescentic glomerulonephritis, minimal change nephropathy with IgA deposition; Renal transplant; Patients with cirrhosis, as assessed by the investigator; 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.; Sitting office SBP>140 mmHg or DBP>90 mmHg during the screening period; HbA1c>8% (64mmol/mol); Treatment with immunosuppressants (cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii, etc.) within 12 weeks prior to randomization; Treatment with anti-CD20 therapy within 24 weeks prior to randomization; Treatment with systemic glucocorticoid within 12 weeks prior to randomization; Hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization; Patients with 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); Patients with hepatitis C; Patients with HIV; 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; Pregnant women, lactating women, and subjects with childbearing plans during the trial; Unavoidable use of drugs with renal toxicity during the study; Allergic to biological products of human origin; Patients who have received any investigational therapy within 4 weeks or within 5 times the half-life of the investigational product (whichever is longer) prior to randomization; Live vaccination within 4 weeks prior to randomization; Patients with COVID-19 infection within 4 weeks of randomization or patients with a history of serious COVID-19 disease requiring hospitalization within 52 weeks prior to screening; Drug or alcohol abuse/dependence within 52 weeks prior to randomization; Not suitable for the study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept<br>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. | Biological: Telitacicept<br>* Telitacicept 240 mg SC<br>* Other names: RC18;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Placebo to Telitacicept<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urine protein creatinine ratio (UPCR) (based on a 24-hour urine sample) at Week 39 | Primary endpoint of phase A | Week 39 | 
| Annualized estimated glomerular filtration rate (eGFR) slope at Week 104 | Primary endpoint of phase B | Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urine protein creatinine ratio (UPCR) (based on a 24-hour urine sample) at weeks 52, 78, and 104 | Change from baseline in UPCR at weeks 52, 78, and 104 | weeks 52, 78, and 104 | 
| Change from baseline in estimated glomerular filtration rate (eGFR) at weeks 39, 52, 78 and 104 | Change from baseline in eGFR at weeks 39, 52, 78 and 104 | weeks 39, 52, 78 and 104 | 
| Change from baseline in urine albumin-to-creatinine ratio (UACR) (based on a 24-hour urine sample) at weeks 39, 52, 78 and 104 | Change from baseline in UACR (based on a 24-hour urine sample) at weeks 39, 52, 78 and 104 | weeks 39, 52, 78 and 104 | 
| Proportion of subjects achieving urine protein creatinine ratio (UPCR) < 0.8 g/g (based on a 24-hour urine sample) at weeks 39, 52, 78 and 104 | Proportion of subjects achieving UPCR < 0.8 g/g (based on a 24-hour urine sample) at weeks 39, 52, 78 and 104 | weeks 39, 52, 78 and 104 | 
| Proportion of patients with a 30% decrease in estimated glomerular filtration rate (eGFR) from baseline at Week 39 | Proportion of patients with a 30% decrease in eGFR from baseline at Week 39 | Week 39 | 
| Annualized estimated glomerular filtration rate (eGFR) slope at Week 52 | Annualized eGFR slope at Week 52 | Week 52 | 
| Time to first occurrence of 30% decrease in estimated glomerular filtration rate (eGFR) | Time to first occurrence of 30% decrease in eGFR since the first dose of the study medicine | up to 104 weeks | 
| Proportion of subjects who received rescue therapy at weeks 52, 78, and 104 | Proportion of subjects who received rescue therapy at weeks 52, 78, and 104 | weeks 52, 78, and 104 | 
| Time to composite endpoint event | The composite endpoint event is defined as initiation of maintenance renal dialysis (for at least 1 month), renal transplant, renal failure (eGFR < 15 mL/min/1.73 m2 or greater than 30% decrease in eGFR from baseline), or death due to renal failure. | up to 104 weeks | 
| Incidence and severity of adverse events | 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. | up to 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Diseases, Autoimmune Diseases, Immune System Diseases