A Phase 3 Multicenter, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate Efficacy and Safety of Mezagitamab (TAK-079) in Study Participants With Primary IgA Nephropathy in Combination With Stable Background Therapy
Immunoglobulin A nephropathy (IgAN) is a kidney condition. It happens when the body's immune system creates groups of proteins (called immune complexes) that build-up in the kidneys causing swelling (inflammation). Over time, this inflammation may lead to kidney damage and cause the kidneys to no longer work properly. The main aim of this study is to check how well mezagitamab changes protein levels in the urine (proteinuria) compared to placebo in adults with primary IgAN. A placebo looks like medicine but doesn't have any active ingredients in it. Other aims are to check how safe mezagitamab is and how well participants with primary IgAN can tolerate it compared to placebo, and to find out if and how well mezagitamab continues to maintain kidney function over the long term compared to placebo. Participants will be placed in 1 of the 2 treatment groups; the main group and the open-label group. In the main group, participants will be placed in 1 of the 2 treatment groups by chance (either mezagitamab or placebo) at a 2:1 ratio. This means that out of 3 participants, 2 will receive mezagitamab and 1 will receive placebo. The participants will receive either mezagitamab or placebo for almost half a year in two 1-year cycles. They will be observed for another half year in each 1-year cycle and will have check-ups about every month during this time. In the open-label group, a small number of participants who have lower levels of protein in their urine or have kidneys that do not filter the blood well, will receive mezagitamab treatment. This will include participants who have previously received mezagitamab in another study, TAK-079-1006. Every participant will receive mezagitamab in the same way as those in the main group receiving mezagitamab. During the study, participants will visit their study clinic several times.
∙ To be eligible to participate in this trial, an individual must meet all the following criteria:
• Either UPCR greater than or equal to (≥) 0.8 gram per gram (g/g) or urine protein excretion (UPE) ≥1 grams per day (g/day), calculated from a 24-hour urine collection during the screening period (only applicable for the main group).
• eGFR greater than (\>)30 milliliters per minute per 1.73 meter square (mL/min/1.73m\^2) at screening based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (only applicable for the main group).
• No prior exposure to anti- cluster of differentiation 38 (CD38) therapy period (only applicable for the main group).
• The participant is at least aged 18 years or the local legal age if greater than 18 years, inclusive.
• The participant (and the participant's legally acceptable representative, if applicable per local regulations or determination) has provided informed consent (that is, in writing, documented via a signed and dated informed consent form \[ICF\]) and any required privacy authorization before the initiation of any clinical trial procedures.
• Renal biopsy report supporting diagnosis of primary IgAN within 10 years before signing informed consent for the clinical trial. The redacted report must be made available for review. A renal biopsy may be performed during screening.
• Participants must be on stable renin-angiotensin-aldosterone system (RAAS) inhibitor therapy with an angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensin receptor blocker (ARB) or endothelin receptor antagonist (ERA) or mineralocorticoid receptor antagonist (MRA) agent for at least 12 weeks before signing the ICF with dosing at the maximally tolerated or labeled dose as determined by the investigator, with the intent to continue stable dosing during the clinical trial. Those intolerant of RAAS inhibitor therapy are potentially eligible after consultation with the medical monitor. Intolerance is defined as a documented side effect causing discontinuation of the therapy.
• Women of childbearing potential who are not pregnant during screening (confirmed by negative serum human chorionic gonadotropin \[hCG\]) and on Visit 1 before first dose of trial intervention (confirmed by negative urine pregnancy test).
• Any one of the following (only applicable for the open-label cohort):
‣ Participants in Study TAK-079-1006 who completed the Week 96 visit or the retreatment period with either UPCR \>0.5 g/g or UPE \>0.5 g/d calculated from a 24-hour urine collection during the screening period and eGFR \>30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.
⁃ UPCR \<0.8 g/g and UPE ≥0.75 and \<1.0 g/day, by 24-hour urine collection during the screening period and eGFR \> 30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.
⁃ UPCR ≥ 0.8 g/g or UPE ≥ 1.0 g/d by 24-hour urine collection during the screening period and eGFR ≥25 and ≤30 mL/min/1.73m\^2 at screening based on the CKD-EPI formula.