Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy

This is a Phase 3, double-blind, randomized, placebo-controlled, study in patients aged 18
years and above with a biopsy-confirmed diagnosis of IgAN and with 24-hour UPE that is > 1
g/day at baseline. During the study, all patients will continue optimized renin-angiotensin
system (RAS) blockade. The study consists of five periods: Screening, Run-In, Initial
Treatment (Weeks 1-12), Response Evaluation (Weeks 13-24), and Follow-Up (Weeks 25-144).
Patients are assessed for re-treatment based on their response to 24-hour UPE. Additional
treatment will be given to patients who relapse or who have partial response following the
Initial Treatment Period.

Approximately 430 patients are to enrolled in two groups of 215 patients per arm.

Inclusion Criteria:

- Age 18 years or older at the onset of Screening

- Biopsy confirmed diagnosis of IgAN within 10 years prior to Screening

- Proteinuria of > 1 g in 24-hour urine collection at Screening and baseline

- Estimated glomerular filtration rate of ≥ 30 and ≤ 90 mL/min/1.73 m2 at Screening and
baseline

- Currently on physician-directed, stable treatment with RAS blockade (ACEIs, ARBs,
direct renin inhibitors) and have a systolic BP of < 150 mmHg and a diastolic BP of <
100 mmHg at rest

Exclusion Criteria:

- Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), cytotoxic
drugs, or eculizumab within 24 weeks prior to Screening

- Unwilling or unable to discontinue systemic corticosteroids 12 weeks prior to
Randomization

- Female patients who are pregnant, breast feeding, or planning to become pregnant up
through 12 weeks after the last dose of study drug, including possible retreatments

- Clinical or biological evidence of diabetes mellitus, systemic lupus erythematosus,
IgA vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease

- History of renal transplantation

- Have a known hypersensitivity to any constituent of the investigational product

- Rapidly progressive glomerulonephritis

- Significant abnormalities in clinical laboratory values

- Body mass index ≥ 35 kg/m²

- History of human immunodeficiency virus (HIV), hepatitis B infection and hepatitis C
infection

- Diagnosis of a malignancy except for adequately treated and cured basal or squamous
cell skin cancer, curatively treated in situ disease, or other cancer from which the
patient has been disease-free for ≥ 5 years

- Have received any other investigational drug or device or experimental procedures
within 30 days of the Screening Visit (SV)