A Study of Mezagitamab in Adults With Kidney Condition Called IgA Nephropathy

• Inclusion Criteria:

To be eligible to participate in this trial, participants must meet all the following criteria:

1. Either UPCR greater than or equal to (≥) 0.8 gram per gram (g/g) or urine proteinexcretion (UPE) ≥1 grams per day (g/day), calculated from at least one 24-hour urinecollection during the screening period (or pre-screening, if applicable) (onlyapplicable for the main trial).

2. 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 EpidemiologyCollaboration (CKD-EPI) formula (only applicable for the main trial).

3. No prior exposure to anti- cluster of differentiation 38 (CD38) therapy period (except for open-label cohort participants meeting Inclusion Criterion No. 10.a).

4. The participant is aged ≥ 18 years or the local legal age as applicable.

5. The participant (and the participant's legally acceptable representative, asapplicable 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 trialprocedures.

6. Diagnosis of primary immunoglobulin A nephropathy (IgAN) supported by a renal biopsyreport that is dated more recently than 10 years before the signing of the informedconsent for the clinical trial. The redacted report must be made available forreview. A renal biopsy must be performed during screening for participants without abiopsy report within 10 years.

7. Participants must be on stable renin-angiotensin-aldosterone system (RAAS) inhibitortherapy with an angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensinreceptor blocker (ARB) or endothelin receptor antagonist (ERA) or mineralocorticoidreceptor antagonist (MRA) agent for at least 12 weeks before signing the ICF withdosing at the maximally tolerated or labeled dose as determined by the investigator,with the intent to continue stable dosing during the clinical trial. Thoseintolerant of RAAS inhibitor therapy are potentially eligible after consultationwith the medical monitor. Intolerance is defined as a documented side effect causingdiscontinuation of the therapy.

8. Resting blood pressure less than or equal to (≤)150 millimeters of mercury (mmHg)systolic and ≤100 mmHg diastolic.

9. Female participants of childbearing potential who are not pregnant during screening (confirmed by negative serum human chorionic gonadotropin [hCG]) and on Visit 1before first dose of trial intervention (confirmed by negative urine pregnancytest).

10. Any one of the following (only applicable for participants in the open-labelcohort):

11. Participants in Trial TAK-079-1006 who completed the Week 96 visit or theretreatment 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 (or pre-screening, ifapplicable) and eGFR >30 mL/min/1.73m^2 at screening based on the CKD-EPIformula.

12. UPCR <0.8 g/g and UPE ≥0.75 and <1.0 g/day, by 24-hour urine collection duringthe screening period (or pre-screening, if applicable) and eGFR > 30mL/min/1.73m^2 at screening based on the CKD-EPI formula.

13. UPCR ≥ 0.8 g/g or UPE ≥ 1.0 g/d by 24-hour urine collection during thescreening period (or pre-screening, if applicable) and eGFR ≥25 and ≤30mL/min/1.73m^2 at screening based on the CKD-EPI formula.

• Exclusion Criteria:

A participant who meets any of the following criteria will be excluded from participation in this trial:

1. Kidney biopsy exhibiting significant concomitant renal disease other than IgAN (forexample, diabetic nephropathy, lupus nephritis, minimal change disease).

2. Secondary IgAN (such as with significant liver disease, inflammatory bowel disease,and seronegative spondyloarthropathies), and immunoglobulin A (IgA) vasculitis.

3. Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3months before the signing of the ICF).

4. Diagnosis of nephrotic syndrome defined as 24-hour proteinuria >3.5 g/day andhypoalbuminemia (<3.0 grams per deciliter [g/dL]) with or without peripheral edema.

5. Renal or other organ transplantation prior to or expected during the clinical trial.

6. Treatment with oral immunosuppressive agents (including cyclophosphamide,mycophenolate mofetil, cyclosporine, azathioprine, calcineurin inhibitors) orbiologic therapy for immunomodulation (including immunomodulatory monoclonal orpolyclonal antibodies) within 6 months (both B-cell and non-B-cell directed agents)before signing of the ICF.

7. If the participant has received anti-CD20 treatment, the participant is excluded ifeither of the following apply:

8. The last dose was received within 6 months before the signing of the ICF.

9. The last dose was received between 6 and 12 months before the signing of theICF and the participant has a CD19+ count below the lower limit of normal. Note: Participants who have received the last dose of anti-CD20 treatment >12 monthsbefore the signing of the ICF are not excluded from clinical trial participationbased on this criterion and are not required to undergo CD19+ testing.

10. Within 4 months of the screening visit, use of either a) systemic corticosteroids atan average dose of 40 milligrams (mg) prednisone equivalent or higher for more than 14 days or b) oral budesonide delayed release capsules.

11. The participant has received a live or live-attenuated vaccine within 4 weeks beforesigning the ICF or has any live or live-attenuated vaccine planned during theclinical trial.

12. Participation in any other investigational drug trial (including vaccine trial) withreceipt of at least 1 dose of investigational drug, or has been exposed to anotherinvestigational agent within 4 weeks or 5 half-lives, whichever is longer, beforeVisit 1.

13. The participant has active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).

14. The participant has had any of the following types of infections within thespecified timeframes where applicable:

15. Active bacterial, viral, or fungal infection (except for the common cold andonychomycosis), or any other serious infection within 2 weeks of signing theICF. Any anti-infective course for infection must be completed at least 2 weeksbefore Visit 1.

16. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection within 4weeks of signing the ICF.

17. Opportunistic infection or treatment for an opportunistic infection less thanor equal to (≤)12 weeks before signing the ICF.

18. Active tuberculosis (TB), any history of prior active TB, or any signs orsymptoms of active TB infection (including but not limited to chronic fever,chronic productive cough, night sweats, weight loss, or malnutrition) as judgedby the investigator.

19. For participants in European Union (EU) member states, positive or 2indeterminant QuantiFERON results, unless there is documentation of priorcomplete treatment for latent TB, or participant has initiated prophylaxisbased on local guidelines and in consultation with a pulmonology or infectiousdisease specialist prior to the first administration of IMP.

20. In the opinion of the investigator, the participant is currently experiencing anymedical condition that might interfere with participation in the trial (for example,significant ocular, cardiovascular, pulmonary, hematologic, gastrointestinal,endocrinologic, hepatic, renal, neurologic, malignancy, infectious disease,immunodeficiency, or alcohol and drug abuse), that poses an added risk for theparticipant or could confound the assessment of trial results.

21. In the opinion of the investigator, the participant has a serious medical orpsychiatric illness that could potentially interfere with the completion oftreatment.

22. The participant has a history of major surgery within 3 months before screening (orlonger, at the discretion of the investigator); or, either has a plannedtonsillectomy or underwent a tonsillectomy within 6 months before screening. Note: Major surgery typically requires at least 1 night in the hospital.

23. History of malignancy (including myelodysplastic syndrome) within 5 years of signingthe ICF, except for adequately treated non-melanoma skin cancer, superficial bladdercancer, and curatively treated cervical carcinoma-in-situ.

24. The participant has a history of a severe allergic or anaphylactic reaction torecombinant proteins or excipients used in the mezagitamab or placebo formulation.

25. The participant has (1) been diagnosed with or has suspected chronic obstructivepulmonary disease (COPD) or asthma and (2) has a prebronchodilatory forcedexpiratory volume in 1 second (FEV1) <50% of predicted normal at screening.

26. The participant is capable of breastfeeding but does not agree to foregobreastfeeding from first dose of investigational medicinal product (IMP) through 30days after the last dose of IMP.

27. The participant is an individual with potential for pregnancy but does not agree touse at least 1 form of highly effective contraception and 1 barrier method ofcontraception (preferably male condom) when engaging in heterosexual sex for theprotocol specified duration after the last dose of IMP.

28. The participant is a sexually active, non-sterilized individual who produces spermbut does not agree to use a barrier method (preferably male condom) combined with atleast 1 form of highly effective contraception for any partner(s) with potential forpregnancy when engaging in heterosexual sex for the protocol specified durationafter the last dose of IMP.

29. In the investigator's opinion, the participant (and the participant's legallyacceptable representative, if applicable per local regulations or determination) isunwilling and/or unable to understand and fully comply with clinical trialprocedures and requirements (including digital tools and applications).