Evaluation of Mezagitamab (TAK-079) Efficacy and Safety in Adults with Primary IgA Nephropathy: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the efficacy of mezagitamab in reducing proteinuria levels at Week 36 in participants with IgA nephropathy compared to those receiving a placebo. Secondary objectives include:

• Determination of the long-term effect of mezagitamab on the change from baseline in estimated glomerular filtration rate (eGFR) at Week 52 and Week 104, a sustained decline in eGFR of ≥30%, and a composite clinical endpoint for kidney failure over 2 years.
• Assessment of the durability of proteinuria reduction following administration.
• Evaluation of the resolution of hematuria over time.
• Determination of the immunogenicity of mezagitamab.
• Characterization of the pharmacokinetic profile of mezagitamab.

This clinical trial involves a total of 264 participants diagnosed with primary immunoglobulin A nephropathy. The study population includes both male and female patients. The participants fall within specific age categories, identified by codes 3 and 4. Inclusion is contingent upon a diagnosis supported by a renal biopsy performed within the last 10 years. Eligible subjects must exhibit a urine protein creatinine ratio of ≥0.8 g/g or urine protein excretion of ≥1 g/day via 24-hour collection. Additionally, participants must have an estimated glomerular filtration rate greater than 30 mL/min/1.73m2 and a resting blood pressure of ≤150 mmHg systolic and ≤100 mmHg diastolic.

This Phase 3, multicenter, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of mezagitamab in adults with primary IgA nephropathy receiving stable background therapy. Participants will be assigned to receive either mezagitamab or a placebo via subcutaneous injection. The primary objective is to assess the change from baseline in proteinuria levels at Week 36, measured by the urine protein creatinine ratio. Secondary endpoints include evaluations of the estimated glomerular filtration rate (eGFR) at Week 52 and Week 104, the resolution of hematuria, and the incidence of anti-drug antibodies. The study involves a screening visit to confirm eligibility based on criteria such as renal biopsy confirmation, specific urine protein excretion levels, and eGFR thresholds. Following screening, participants undergo the intervention period with assessments at scheduled intervals, including follow-up visits to monitor kidney function and safety through Week 104. The total duration of participant involvement is determined by the assessment schedule extending to the end-of-study visit.

Mezagitamab is an investigational solution for injection. This experimental medication is administered via subcutaneous injection to participants diagnosed with IgA nephropathy.

The control group receives a placebo-matching injection administered via the subcutaneous route. This placebo is utilized in combination with stable background therapy to maintain the double-blind design of the study.

The efficacy of mezagitamab in participants with primary immunoglobulin A nephropathy is evaluated using several endpoints. The primary endpoint is the change from baseline in proteinuria at Week 36, which is assessed via the urinary protein-to-creatinine ratio (UPCR) calculated from a 24-hour urine collection.

Secondary efficacy assessments include:

• Changes from baseline in estimated glomerular filtration rate (eGFR) at Week 52 and Week 104, including the eGFR total slope.
• Time from baseline to the first occurrence of a sustained decline in eGFR of ≥30% for at least 4 weeks.
• Time from baseline to the first occurrence of a kidney failure composite endpoint, which includes sustained eGFR decline, sustained eGFR <15 mL/min/1.73 m2, initiation of maintenance dialysis, kidney transplant, or death from kidney failure.
• Changes from baseline in proteinuria levels at Week 104.
• Resolution of hematuria at Week 36, Week 52, and Week 104.
• Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb).
• Serum concentrations of mezagitamab during and after the intervention period.