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

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)

The primary objective of this study is to evaluate the effect of OMS721 on 24-hour urine protein excretion (UPE) in IgA nephropathy (IgAN) patients with high baseline proteinuria (high-risk proteinuria group; 24-hour UPE ≥ 2 g/day) assessed at 36 weeks from baseline.

Study Overview

• Status: Terminated
• Conditions: IgA Nephropathy
• Intervention / Treatment: Biological: OMS721; Other: Vehicle (D5W or saline)

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. The purpose of this study is to evaluate the efficacy and safety of narsoplimab (OMS721) compared to placebo on proteinuria and whether narsoplimab has the ability to slow disease progression in primary IgAN patients. The primary objective of the study is to evaluate proteinuria reduction as assessed by 24-hour UPE at 36 weeks from baseline. The trial will continue beyond 36 weeks in a blinded fashion to provide confirmatory evidence of long-term efficacy based on the annualized slope of eGFR over 24 months. The trial will enroll approximately 450 patients with 225 patients per arm, all having biopsy-proven IgAN with eGFR≥30 mL/min/1.73m2 and 24 hour UPE >1g/day. The study duration for each patient is expected to last approximately 112 weeks.

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Omeros Investigational Site
  • Cordoba, Argentina, X5016KEH
    • Omeros Investigational Site
  • Salta, Argentina, 4400
    • Omeros Investigational Site
  • Misiones
    • Posadas, Misiones, Argentina, 3300
      • Omeros Investigational Site
• Australia
  • Australian Capital Territory, Woden
    • Garran, Australian Capital Territory, Woden, Australia, 2606
      • Omeros Investigational Site
  • Saint Albans
    • Footscray, Saint Albans, Australia, 3021
      • Omeros Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Omeros Investigational Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Omeros Investigational Site
• Belgium
  • Gent, Belgium, 9000
    • Omeros Investigational Site
  • Leuven, Belgium, 3000
    • Omeros Investigational Site
  • Liège, Belgium, 1-4000
    • Omeros Investigational Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Omeros Investigational Site
  • Plovdiv, Bulgaria, 4002
    • Omeros Investigational Site
  • Sofia, Bulgaria, 1431
    • Omeros Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z2M9
      • Omeros Investigational Site
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Omeros Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A545
      • Omeros Investigational Site
    • Toronto, Ontario, Canada, M5G2C4
      • Omeros Investigational Site
• Czechia
  • Praha
    • Prague, Praha, Czechia, 128 08
      • Omeros Investigational Site
• Germany
  • Göttingen, Germany, 37075
    • Omeros Investigational Site
  • Villingen-Schwenningen, Germany, 78052
    • Omeros Investigational Site
  • Baden-Wrttemberg
    • Mannheim, Baden-Wrttemberg, Germany, 68167
      • Omeros Investigational Site
  • Bayern
    • München, Bayern, Germany, 80336
      • Omeros Investigational Site
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Omeros Investigational Site
• Greece
  • Athens, Greece, 11527
    • Omeros Investigational Site
  • Heraklion, Greece, 71110
    • Omeros Investigational Site
  • Iraklio, Greece, 71409
    • Omeros Investigational Site
  • Patra, Greece, 26504
    • Omeros Investigational Site
  • Pilea-Chortiatis
    • Thessaloniki, Pilea-Chortiatis, Greece, 57010
      • Omeros Investigational Site
• Hungary
  • Baja, Hungary, H-6500
    • Omeros Investigational Site
  • Budapest, Hungary, H-1097
    • Omeros Investigational Site
  • Gyor, Hungary, H-9024
    • Omeros Investigational Site
  • Pecs, Hungary, H-7624
    • Omeros Investigational Site
  • Szeged, Hungary, 6720
    • Omeros Investigational Site
• India
  • Chandigarh, India, 160012
    • Omeros Investigational Site
  • Ameerpet
    • Hyderabad, Ameerpet, India, 500038
      • Omeros Investigational Site
  • Gujarat
    • Nadiad, Gujarat, India, 387001
      • Omeros Investigational Site
  • Karnataka
    • Belagam, Karnataka, India, 590010
      • Omeros Investigational Site
    • Mangalore, Karnataka, India, 575001
      • Omeros Investigational Site
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Omeros Investigational Site
  • New India
    • New Delhi, New India, India, 110017
      • Omeros Investigational Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Omeros Investigational Site
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Omeros Investigational Site
    • Hyderabad, Telangana, India, 500038
      • Omeros Investigational Site
    • Hyderabad, Telangana, India, 500082
      • Omeros Investigational Site
• Italy
  • Bari, Italy, 70124
    • Omeros Investigational Site
  • Bergamo, Italy, 24127
    • Omeros Investigational Site
  • Eboli, Italy, 84025
    • Omeros Investigational Site
  • Messina, Italy, 98125
    • Omeros Investigational Site
  • Milano, Italy, 20122
    • Omeros Investigational Site
  • Modena, Italy, 41124
    • Omeros Investigational Site
  • Parma, Italy, 43126
    • Omeros Investigational Site
  • Piacenza, Italy, 29121
    • Omeros Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Omeros Investigational Site
  • Incheon, Korea, Republic of, 21431
    • Omeros Investigational Site
  • Seoul, Korea, Republic of, 05278
    • Omeros Investigational Site
  • Seoul, Korea, Republic of, 07061
    • Omeros Investigational Site
  • Seoul, Korea, Republic of, 3080
    • Omeros Investigational Site
  • Seoul, Korea, Republic of, 3722
    • Omeros Investigational Site
  • Geyonggi-do
    • Seongnam, Geyonggi-do, Korea, Republic of, 13496
      • Omeros Investigational Site
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, Korea, Republic of, 14068
      • Omeros Investigational Site
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Omeros Investigational Site
  • Vilnius, Lithuania, LT-08661
    • Omeros Investigational Site
• Poland
  • Krakow, Poland, 30-688
    • Omeros Investigational Site
  • Olsztyn, Poland, 10-561
    • Omeros Investigational Site
  • Warszawa, Poland, 04-749
    • Omeros Investigational Site
  • Todzi
    • Łódź, Todzi, Poland, 92-213
      • Omeros Investigational Site
• Singapore
  • Singapore, Singapore, 119074
    • Omeros Investigational Site
  • Singapore, Singapore, 308433
    • Omeros Investigational Site
• Slovakia
  • Banská Bystrica, Slovakia, 97401
    • Omeros Investigational Site
  • Kosice, Slovakia, 04011
    • Omeros Investigational Site
• Spain
  • Almeria, Spain, 04009
    • Omeros Investigational Site
  • Barcelona, Spain, 08025
    • Omeros Investigational Site
  • Cordoba, Spain, 14004
    • Omeros Investigational Site
  • Lleida, Spain, 25198
    • Omeros Investigational Site
  • Madrid, Spain, 28040
    • Omeros Investigational Site
  • Madrid, Spain, 28041
    • Omeros Investigational Site
  • Valencia, Spain, 46026
    • Omeros Investigational Site
  • Zaragoza, Spain, 50009
    • Omeros Investigational Site
  • San Sebastian De Lost Reyes
    • Madrid, San Sebastian De Lost Reyes, Spain, 28702
      • Omeros Investigational Site
• Sweden
  • Stockholm, Sweden
    • Omeros Investigational Site
• Taiwan
  • Changhua City, Taiwan, 500
    • Omeros Investigational Site
  • Hualien City, Taiwan, 97002
    • Omeros Investigational Site
  • Kaohsiung City, Taiwan, 824
    • Omeros Investigational Site
  • New Taipei City, Taiwan, 220
    • Omeros Investigational Site
  • New Taipei City, Taiwan, 235
    • Omeros Investigational Site
  • Taichung City, Taiwan
    • Omeros Investigational Site
  • Taoyuan City, Taiwan, 333
    • Omeros Investigational Site
• Thailand
  • Bangkok, Thailand, 10300
    • Omeros Investigational Site
  • Bangkok, Thailand, 10700
    • Omeros Investigational Site
  • Chiang Mai, Thailand, 50200
    • Omeros Investigational Site
  • Dusit, Thailand
    • Omeros Investigational Site
  • Khon Kaen, Thailand, 40000
    • Omeros Investigational Site
  • Songkla, Thailand, 90000
    • Omeros Investigational Site
• Turkey
  • Ankara, Turkey, 06230
    • Omeros Investigational Site
  • Bursa, Turkey, 16059
    • Omeros Investigational Site
  • Edirne, Turkey, 22130
    • Omeros Investigational Site
  • Istanbul, Turkey, 34899
    • Omeros Investigational Site
  • Kocaeli, Turkey, 41380
    • Omeros Investigational Site
  • Malatya, Turkey, 44200
    • Omeros Investigational Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Omeros Investigational Site
  • Cardiff, United Kingdom, CF10 3XQ
    • Omeros Investigational Site
  • Dartford, United Kingdom, DA2 8DA
    • Omeros Investigational Site
  • London, United Kingdom, NW3 2QG
    • Omeros Investigational Site
  • Evington
    • Leicester, Evington, United Kingdom, LE5 4PW
      • Omeros Investigational Site
• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Omeros Investigational Site
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Omeros Investigational Site
    • Phoenix, Arizona, United States, 85016
      • Omeros Investigation Sites
    • Scottsdale, Arizona, United States, 85258
      • Omeros Investigational Site
    • Scottsdale, Arizona, United States, 85259
      • Omeros Investigational Site
  • California
    • Los Angeles, California, United States, 90022-4302
      • Omeros Investigational Site
    • Los Angeles, California, United States, 90025
      • Omeros Investigational Site
    • Northridge, California, United States, 91324
      • Omeros Investigational Site
    • San Dimas, California, United States, 91773
      • Omeros Investigational Site
    • San Francisco, California, United States, 94118
      • Omeros Investigational Site
    • Stanford, California, United States, 94304
      • Omeros Investigational Site
    • Torrance, California, United States, 90509
      • Omeros Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Omeros Investigational Site
  • Florida
    • Miami, Florida, United States, 33136
      • Omeros Investigational Site
    • Miami Lakes, Florida, United States, 33014
      • Omeros Investigational Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Omeros Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Omeros Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Omeros Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Omeros Investigational Site
    • Springfield, Massachusetts, United States, 01107
      • Omeros Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Omeros Investigational Site
    • Rochester, Minnesota, United States, 55905
      • Omeros Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Omeros Investigational Site
  • New York
    • Fresh Meadows, New York, United States, 11365
      • Omeros Investigational Site
    • New York, New York, United States, 10029
      • Omeros Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Omeros Investigational Site
    • Columbus, Ohio, United States, 43210
      • Omeros Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Omeros Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Omeros Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Omeros Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Omeros Investigational Site
    • Dallas, Texas, United States, 75246
      • Omeros Investigational Site
    • Houston, Texas, United States, 77054
      • Omeros Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Omeros Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. Males who are planning to father children 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 and/or treatments within 30 days of the Screening Visit (SV)
• Initiation or change in dosing of sodium glucose co-transporter 2 inhibitors (SGLT2i) during Screening and Run-In Periods. However, a stable dose regimen established at least 8 weeks prior to screening is acceptable
• Treatment with Tarpeyo™ (budesonide) or other approved treatments for IgAN within 6 months prior to screening. Treatment with Tarpeyo is not allowed during Screening and Run-In Periods
• Treatment with Kerendia® (finerenone) within 6 months prior to screening. Treatment with Kerendia is not allowed during Screening and Run-In Periods
• Initiation of treatment with Filspari™ (sparsentan), a dual Endothelin Angiotensin Receptor Antagonist (dEARA) or similar medication within three months prior to screening. A stable dose initiated at minimum 3 months before screening is acceptable and will take the place of ACEi/ARB as background therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in 24-hour UPE in IgA nephropathy (IgAN) patients assessed at 36 weeks from baseline	36 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function as determined by the rate of change in eGFR at up to 96 weeks from baseline.		96 Weeks
Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks		36 and 48 Weeks
Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 and 72 weeks		36 and 72 Weeks
Safety and tolerability of narsoplimab for the treatment of IgAN	As assessed by the incidence of adverse events through study completion (Week 112) in the patient group with baseline 24-hour UPE ≥ 2 g and in the all-patients population	Week 112
Pharmacokinetics of narsoplimab intravenous infusion	By evaluating the maximum concentration (Cmax) parameters at baseline and study days, T1, T4, T8, T10, T12 population (24-hour UPE > 1 g/day)	Week 12
Assessment of pharmacokinetics of narsoplimab intravenous infusion	By evaluating the area under the concentration-time curve from dosing time (AUC) at baseline and study days, T1, T4, T8, T10,T12	Week 12
Pharmacokinetics of narsoplimab intravenous infusion	Pharmacokinetics of narsoplimab intravenous infusion by evaluating the maximum concentration Cmax parameters at baseline and study days, T1 Weeks 1, T4 Week 2-11, T8 Week 2-11, T10 Week 2-11, T12 Week 12 ±2 days measurement of anti-drug antibodies and neutralizing antibodies at baseline and study days T1, T4, T8, T10, T12	Week 12
Assessment of pharmacodynamics of narsoplimab intravenous infusion	Assessment of pharmacokinetics of narsoplimab intravenous infusion by evaluating the area under the concentration-time curve from dosing time AUC at baseline and study days, T1 Weeks 1, T4 Week 2-11, T8 Week 2-11, T10 Week 2-11, T12 Week 12 ±2 days	Week 12
Assessment of pharmacodynamics of narsoplimab intravenous infusion with presence of positive anti-drug antibodies	Assessment of percentage of participants with presence of positive anti-drug antibodies following intravenous infusion of narsoplimab at baseline and study days T1 Weeks 1, T4 Week 2-11, T8 Week 2-11, T10 Week 2-11, T12 Week 12 ±2 days.	Week 12
Assessment of percentage of participants with presence of neutralizing antibodies	Assessment of percentage of participants with presence of neutralizing antibodies following intravenous infusion of narsoplimab at baseline and study days T1 Weeks 1, T4 Week 2-11, T8 Week 2-11, T10 Week 2-11, T12 Week 12 ±2 days.	Week 12
Change from baseline in log-transformed 24-hour uPCR through 36 weeks.		Week 36

Collaborators and Investigators

• Sponsor: Omeros Corporation

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): October 16, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: June 21, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Proteinuria; IgA nephropathy; eGFR; IgAN; Narsoplimab; IgAN autoantibodies; EGFR slope; UPE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: OMS721-IGA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No