Efficacy and Safety of Telitacicept in IgAN

Official title

A Multicenter, Randomized, Controlled Clinical Study on the Efficacy and Safety of Telitacicept in Patients with IgA Nephropathy

Overview

A study to evaluate efficacy and safety of telitacicept in the treatment of patients with primary IgA nephropathy at high risk of progression.

Detailed description

IgA nephropathy is a glomerulonephritis characterized by pathological IgA deposition in the mesangial region. Its clinical and pathological manifestations are diverse and heterogeneous. Its pathogenesis has not yet been fully clarified, and there is currently no unified treatment plan. As a recombinant human B lymphocyte stimulator receptor-antibody fusion protein, telitacicept has become a new therapeutic target. The results of the Phase II clinical trial of this drug for IgA nephropathy have already been published. It is one of the key pioneering clinical studies in the field of IgA nephropathy treatment. The study showed that telitacicept can effectively reduce patients' proteinuria and reduce the risk of disease progression. Based on the above research results, the investigators plan to conduct a multicenter, randomized, controlled clinical study to evaluate the efficacy and safety of telitacicept in the treatment of primary IgA nephropathy patients with a high risk of progression.

Interventions

• Drug Telitacicept 240mg
  Patients in telitacicept group will be treated with maximum tolerable dose of angiotensin converting enzyme inhibitor ( ACEI ) and/or angiotensin II receptor blocker ( ARB ) combined with telitacicept. 240 mg telitacicept will be used once a week for 40 weeks.
• Drug Glucocorticoid
  Patients in glucocorticoid group will be treated with ACEI/ARB and glucocorticoid ( prednisone/prednisolone) 0.5mg/kg (maximum 40mg/d). After 8 weeks, reduce the dosage by 5 mg per month for a total of 28-40 weeks.

Primary outcome measures

• Change of 24-hour urine protein [Time frame: From baseline to week 40]

Secondary outcome measures (8)

• Change of PCR [Time frame: From baseline to week 40]
• Annualized eGFR slope [Time frame: From baseline to week 40]
• Change of eGFR [Time frame: From baseline to week 40]
• Proportion of patients with a decrease in eGFR ≥30% [Time frame: From baseline to week 40]
• Proportion of patients with a decrease in eGFR ≥40% [Time frame: From baseline to week 40]
• Change of 24-hour urine ACR [Time frame: From baseline to week 40]
• Proportion of patients achieving 24-hour urine PCR < 0.6 g/g [Time frame: From baseline to week 40]
• Time from the first use of treatment to the occurrence of a composite endpoint event [Time frame: Up to 40 weeks]

Eligibility criteria

Inclusion criteria

• 18-70 years old, male or female
• Primary IgA nephropathy confirmed by renal biopsy.
• Urine protein ≥ 0.75g/24h or 24-hour urine protein creatinine ratio (PCR) ≥ 0.6 g/g.
• eGFR ≥ 25 ml/min/1.73 m2 calculated using the CKD-EPI formula.
• Received treatment with ACEI/ARB for 12 weeks before randomization, and the drug dose (within the maximum tolerated range) was stable within 4 weeks before randomization.
• Use of SGLT2, MRA, hydroxychloroquine, and etc. remained unchanged.
• Voluntarily participated in this study and signed the informed consent form.

Exclusion criteria

• Patients with abnormal laboratory indicators (see study protocol for details).
• Secondary IgA nephropathy such as Henoch-Schonlein purpura, SLE, cirrhosis, etc.
• Use of systemic glucocorticoids/immunosuppressants within 3 months (such as cyclophosphamide, azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, tripterygium wilfordii, etc.).
• Use of biological agents within 6 months (rituximab, etc.).
• Active infection, such as active tuberculosis, active hepatitis, hepatitis C, herpes zoster, HIV, etc. According to the results of the five hepatitis B test: patients with positive HBsAg should be excluded; patients with negative HBsAg but positive HBcAb, regardless of whether HBsAb is positive or negative, need to test HBV-DNA to determine their situation: if HBV-DNA is positive, the patient needs to be excluded; if HBV-DNA is negative, the patient can participate in the trial.
• COVID-19 infection within 2 weeks before randomization.
• Live vaccine within 4 weeks before randomization.
• History of malignant tumor within five years.
• Uncontrolled hypertension (systolic blood pressure>140mmHg or diastolic blood pressure>90mmHg).
• Poorly controlled diabetes (glycosylated hemoglobin>8%).
• Pregnant women and breastfeeding women.
• Participating in other clinical trials at the same time.
• Surgery, chemotherapy, radiotherapy and other treatments are planned during the study.
• Other reasons judged by researchers as unsuitable for inclusion in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital — Shanghai

Identifiers

NCT: NCT06654596 · TETA-IgA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗