Inclusion Criteria:

• Patients ≥ 18 to ≤ 80 years (at date of signing the informed consent form [ICF]), but at least of legal age in the given country.
• Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF.
• Proteinuria at screening visit ≥ 1.0 g/d.
• Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for ≥ 3 months prior to date of informed consent and adequate blood pressure (BP) control (recommended BP is < 125 mm Hg systolic and < 75 mm Hg diastolic) In case a patient is intolerant to even a very low dose of either ACEi or ARB therapy, approval for participation in the trial has to be obtained from the Medical Monitor prior to randomization.
• A female of childbearing potential (FCBP) is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of Felzartamab.

Exclusion Criteria:

• Secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits (e.g., Lupus nephritis, Schönlein-Henoch purpura, ankylosing spondylitis, dermatitis herpetiformis, chronic liver disease, inflammatory bowel disease, celiac disease).
• Severe renal impairment as defined by estimated GFR < 30 mL/min (using chronic kidney disease-epidemiology collaboration [CKD-EPI] formula) or the need for dialysis or renal transplant.
• Rapidly progressive variant of IgAN, defined as eGFR loss by more than 30% per 3 months and not explained by changes in renin angiotensin system (RAS) blockade.
• Minimal change variant of IgAN.
• Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
• Systemic immunosuppression (e.g. mycophenolate mofetil [MMF], cyclophosphamide, biologics like rituximab [RTX]), in particular corticosteroid therapy exceeding 20 mg/day prednisone-equivalent for more than 7 consecutive days within 180 days prior to signing ICF.
• Any previous treatment with an anti-CD38 antibody.
• Body mass index (BMI) > 35 kg/m^2.
• Hemoglobin < 90 g/L.
• Thrombocytopenia: Platelets < 100.0 x 10^9 /L.
• Neutropenia: Neutrophils < 1.5 x 10^9 /L.
• Leukopenia: Leukocytes < 3.0 x 10^9 /L.
• Diabetes mellitus type 1.
• Diabetes mellitus type 2:
  • Patients with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to signing ICF shows IgAN without evidence of diabetic nephropathy and their disease is controlled, such as:
    • Glycated hemoglobin (HbA1c) < 8.0% or < 64 mmoL/mol.;
    • No diabetic retinopathy known;
    • No peripheral neuropathy known.
• Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
• Clinically significant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
• History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity ≥ grade 3.
• Aspartate aminotransferase or alanine aminotransferase > 1.5 x ULN, alkaline phosphatase > 3.0 x ULN.
• Known or suspected hypersensitivity to Felzartamab and its excipients (L-histidine, sucrose, polysorbate 20).
• Serologic markers positive for HIV or history of HIV, hepatitis C (patients with positive anti-hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). For patients with positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll).
• Any malignancy within 5 years prior to screening start, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or other non-melanomatous skin cancer.
• Treatment within 5 terminal half-lives (if known) or within the last 30 days prior to Visit 2, whatever is longer) with investigational drugs.
• Any active infection (viral, fungal, bacterial) requiring systemic therapy.

Eligibility last updated 1/19/22. Questions regarding updates should be directed to the study team contact.