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

• ClinicalTrials.gov Identifier: NCT03608033
• Recruitment Status: Recruiting
• First Posted: July 31, 2018
• Last Update Posted: May 30, 2019
• Sponsor: Omeros Corporation
• Information provided by (Responsible Party): Omeros Corporation

Tracking Information

• First Submitted Date: June 21, 2018
• First Posted Date: July 31, 2018
• Last Update Posted Date: May 30, 2019
• Actual Study Start Date: February 16, 2018
• Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 28, 2019): Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment [ Time Frame: 36 Weeks ]
• Original Primary Outcome Measures (submitted: July 23, 2018): Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 24 weeks from beginning of treatment [ Time Frame: 24 Weeks ]

Current Secondary Outcome Measures (submitted: May 28, 2019)

• Number of patients with treatment related Adverse Events as assessed by CTCAE v 4.0 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 36 Weeks ]
• Time-averaged change in urine protein/creatinine ratio (uPCR) through 36 weeks. [ Time Frame: 36 Weeks ]

Original Secondary Outcome Measures (submitted: July 23, 2018)

• Number of patients with treatment related Adverse Events as assessed by CTCAE v 4.0 [ Time Frame: 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 [ Time Frame: 144 Weeks ]
• Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 24 weeks from beginning of treatment in the subset of patients with baseline high proteinuria (defined as 24-hour UPE ≥ 2 g/day) [ Time Frame: 24 Weeks ]
• Time-averaged change in urine protein/creatinine ratio (uPCR) through 24 weeks. [ Time Frame: 24 Weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy
• Official Title: 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)
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible patients will be randomized 1:1 to receive OMS721 or placebo

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: IgA Nephropathy

Intervention

• Biological: OMS721
  Biological: OMS721
• Other: Vehicle (D5W or saline)
  5% Dextrose in water or normal saline solution

Study Arms

• Experimental: OMS721
  Administration of OMS721
  Intervention: Biological: OMS721
• Placebo Comparator: Placebo
  Administration of Vehicle (D5W or Saline Solution)
  Intervention: Other: Vehicle (D5W or saline)

• Publications *: Reich HN, Floege J. How I Treat IgA Nephropathy. Clin J Am Soc Nephrol. 2022 Aug;17(8):1243-1246. doi: 10.2215/CJN.02710322. Epub 2022 Jun 8. No abstract available.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 28, 2019): 450
• Original Estimated Enrollment (submitted: July 23, 2018): 430
• Estimated Study Completion Date: April 2023
• Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Laura Haas; (206) 676-0886; lhaas@omeros.com

Contact: Fay Wang; (206) 676-0863; fwang@omeros.com

• Listed Location Countries: Australia, Austria, Belgium, Bulgaria, Hungary, Lithuania, Poland, Slovakia, Spain, United States

Administrative Information

• NCT Number: NCT03608033
• Other Study ID Numbers: OMS721-IGA-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Omeros Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Omeros Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Omeros Corporation
• Verification Date: May 2019