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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of OMS721 in patients with IgA nephropathy. The study will assess proteinuria by 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment.

Detailed Description
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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 within 6 months prior to Screening or uPCR > 0.75 by spot urine at Screening. 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 13-36), and Follow-Up (Weeks 37-144). Patients are assessed for re-treatment based on their response to 24-hour UPE. Additional treatment may be given to patients whose 24-hour UPE is > 1 g/day following the Initial Treatment Period and who relapse during the Response Evaluation and Follow-Up periods. Patients may be qualified for Open-Label Treatment with OMS721 after Week 72. Approximately 450 patients are to enrolled in two groups of 225 patients per arm.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy (ARTEMIS - IGAN)

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Biological: OMS721
* Other: Vehicle (D5W or saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older at the onset of Screening Biopsy confirmed diagnosis of IgAN within 8 years prior to Screening Proteinuria of > 1 g/day within 6 months prior to Screening or uPCR > 0.75 by spot urine at Screening Mean of two proteinuria measurements > 1 g/day at baseline Estimated glomerular filtration rate of ≥ 30 mL/min/1.73 m2 at Screening and baseline Exclusion Criteria: Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), or cytotoxic drugs, for IgA within 8 weeks prior to Screening. Treatment with immunosuppressants or cytotoxic drugs for IgAN is not allowed during the Run-In Period. Treatment with immunosuppressants are allowed if such treatment is for indications other than IgAN. Treatment with eculizumab within 8 weeks prior to Screening. Treatment with eculizumab is not allowed during the Run-In Period. Treatment with systemic corticosteroids within 8 weeks prior to Screening. Treatment with systemic corticosteroids is not allowed during the Run-In Period. Uncontrolled BP, a systolic BP of > 150 mmHg and a diastolic BP of > 100 mmHg at rest despite the combination of two or more anti-hypertensives including ACEIs, ARBs, or direct renin inhibitors at Screening and baseline 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 Type 1 diabetes mellitus (DM), or poorly controlled DM with hemoglobin A1c > 7.5 or with evidence of diabetic nephropathy on biopsy, systemic lupus erythematosus, IgA vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease during Screening and Run-In History of renal transplantation Have a known hypersensitivity to any constituent of the investigational product Rapidly progressive glomerulonephritis Significant abnormalities in clinical laboratory values History of human immunodeficiency virus (HIV), evidence of immune suppression, active HCV infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), HBV infection (patients with positive HBsAg are excluded. For patients with isolated positive anti-HBc antibody, HBV DNA test by PCR must be non-detectable to enroll). 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients will be randomized 1:1 to receive OMS721 or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMS721<br>Administration of OMS721 | Biological: OMS721<br>* Biological: OMS721<br>|
| Placebo Comparator: Placebo<br>Administration of Vehicle (D5W or Saline Solution) | Other: Vehicle (D5W or saline)<br>* 5% Dextrose in water or normal saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment |  | 36 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment related Adverse Events as assessed by CTCAE v 4.0 |  | 168 Weeks | 
| Change from baseline in renal function as determined by the rate of change in estimated glomerular filtration rate (eGFR) up to 144 weeks from beginning of treatment |  | 144 Weeks | 
| Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment in the subset of patients with baseline high proteinuria (defined as 24-hour UPE ≥ 2 g/day) |  | 36 Weeks | 
| Time-averaged change in urine protein/creatinine ratio (uPCR) through 36 weeks. |  | 36 Weeks |