Clinical trial NCT03608033: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: IgA Nephropathy
Keywords: IgA nephropathy
IgAN
Proteinuria
Chronic kidney disease
IgAN autoantibodies
eGFR
EGFR slope
UPE
Narsoplimab
Lead sponsor: Omeros Corporation
Sponsor class: INDUSTRY
First posted: 2018-07-31
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomized 1:1 to receive OMS721 or placebo
Primary purpose: TREATMENT

Brief summary: 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.

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.

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. 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

Primary outcomes:
measure: Change from baseline in 24-hour UPE in IgA nephropathy (IgAN) patients assessed at 36 weeks from baseline
timeFrame: 36 Weeks
Secondary outcomes:
measure: Renal function as determined by the rate of change in eGFR at up to 96 weeks from baseline.
timeFrame: 96 Weeks
measure: Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks
timeFrame: 36 and 48 Weeks
measure: Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 and 72 weeks
timeFrame: 36 and 72 Weeks
measure: Safety and tolerability of narsoplimab for the treatment of IgAN
timeFrame: Week 112
measure: Pharmacokinetics of narsoplimab intravenous infusion
timeFrame: Week 12
measure: Assessment of pharmacokinetics of narsoplimab intravenous infusion
timeFrame: Week 12
measure: Pharmacokinetics of narsoplimab intravenous infusion
timeFrame: Week 12
measure: Assessment of pharmacodynamics of narsoplimab intravenous infusion
timeFrame: Week 12
measure: Assessment of pharmacodynamics of narsoplimab intravenous infusion with presence of positive anti-drug antibodies
timeFrame: Week 12
measure: Assessment of percentage of participants with presence of neutralizing antibodies
timeFrame: Week 12
measure: Change from baseline in log-transformed 24-hour uPCR through 36 weeks.
timeFrame: Week 36
Other outcomes:
Locations:
city: Florence
country: United States
facility: Omeros Investigational Site
state: Alabama
city: Mesa
country: United States
facility: Omeros Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Omeros Investigation Sites
state: Arizona
city: Scottsdale
country: United States
facility: Omeros Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: Omeros Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: Omeros Investigational Site
state: California
city: Los Angeles
country: United States
facility: Omeros Investigational Site
state: California
city: Northridge
country: United States
facility: Omeros Investigational Site
state: California
city: San Dimas
country: United States
facility: Omeros Investigational Site
state: California
city: San Francisco
country: United States
facility: Omeros Investigational Site
state: California
city: Stanford
country: United States
facility: Omeros Investigational Site
state: California
city: Torrance
country: United States
facility: Omeros Investigational Site
state: California
city: Denver
country: United States
facility: Omeros Investigational Site
state: Colorado
city: Miami Lakes
country: United States
facility: Omeros Investigational Site
state: Florida
city: Miami
country: United States
facility: Omeros Investigational Site
state: Florida
city: Lawrenceville
country: United States
facility: Omeros Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Omeros Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Omeros Investigational Site
state: Iowa
city: Boston
country: United States
facility: Omeros Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Omeros Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Omeros Investigational Site
state: Minnesota
city: Rochester
country: United States
facility: Omeros Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: Omeros Investigational Site
state: Missouri
city: Fresh Meadows
country: United States
facility: Omeros Investigational Site
state: New York
city: New York
country: United States
facility: Omeros Investigational Site
state: New York
city: Cincinnati
country: United States
facility: Omeros Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Omeros Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: Omeros Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Omeros Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Omeros Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Omeros Investigational Site
state: Texas
city: Dallas
country: United States
facility: Omeros Investigational Site
state: Texas
city: Houston
country: United States
facility: Omeros Investigational Site
state: Texas
city: Milwaukee
country: United States
facility: Omeros Investigational Site
state: Wisconsin
city: Posadas
country: Argentina
facility: Omeros Investigational Site
state: Misiones
city: Buenos Aires
country: Argentina
facility: Omeros Investigational Site
city: Cordoba
country: Argentina
facility: Omeros Investigational Site
city: Salta
country: Argentina
facility: Omeros Investigational Site
city: Garran
country: Australia
facility: Omeros Investigational Site
state: Australian Capital Territory, Woden
city: Footscray
country: Australia
facility: Omeros Investigational Site
state: Saint Albans
city: Adelaide
country: Australia
facility: Omeros Investigational Site
state: South Australia
city: Clayton
country: Australia
facility: Omeros Investigational Site
state: Victoria
city: Gent
country: Belgium
facility: Omeros Investigational Site
city: Leuven
country: Belgium
facility: Omeros Investigational Site
city: Liège
country: Belgium
facility: Omeros Investigational Site
city: Plovdiv
country: Bulgaria
facility: Omeros Investigational Site
city: Plovdiv
country: Bulgaria
facility: Omeros Investigational Site
city: Sofia
country: Bulgaria
facility: Omeros Investigational Site
city: Vancouver
country: Canada
facility: Omeros Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Omeros Investigational Site
state: British Columbia
city: London
country: Canada
facility: Omeros Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Omeros Investigational Site
state: Ontario
city: Prague
country: Czechia
facility: Omeros Investigational Site
state: Praha
city: Mannheim
country: Germany
facility: Omeros Investigational Site
state: Baden-Wrttemberg
city: München
country: Germany
facility: Omeros Investigational Site
state: Bayern
city: Aachen
country: Germany
facility: Omeros Investigational Site
state: Nordrhein-Westfalen
city: Göttingen
country: Germany
facility: Omeros Investigational Site
city: Villingen-Schwenningen
country: Germany
facility: Omeros Investigational Site
city: Thessaloniki
country: Greece
facility: Omeros Investigational Site
state: Pilea-Chortiatis
city: Athens
country: Greece
facility: Omeros Investigational Site
city: Heraklion
country: Greece
facility: Omeros Investigational Site
city: Iraklio
country: Greece
facility: Omeros Investigational Site
city: Patra
country: Greece
facility: Omeros Investigational Site
city: Baja
country: Hungary
facility: Omeros Investigational Site
city: Budapest
country: Hungary
facility: Omeros Investigational Site
city: Gyor
country: Hungary
facility: Omeros Investigational Site
city: Pecs
country: Hungary
facility: Omeros Investigational Site
city: Szeged
country: Hungary
facility: Omeros Investigational Site
city: Hyderabad
country: India
facility: Omeros Investigational Site
state: Ameerpet
city: Nadiad
country: India
facility: Omeros Investigational Site
state: Gujarat
city: Belagam
country: India
facility: Omeros Investigational Site
state: Karnataka
city: Mangalore
country: India
facility: Omeros Investigational Site
state: Karnataka
city: Kozhikode
country: India
facility: Omeros Investigational Site
state: Kerala
city: New Delhi
country: India
facility: Omeros Investigational Site
state: New India
city: Jaipur
country: India
facility: Omeros Investigational Site
state: Rajasthan
city: Hyderabad
country: India
facility: Omeros Investigational Site
state: Telangana
city: Hyderabad
country: India
facility: Omeros Investigational Site
state: Telangana
city: Hyderabad
country: India
facility: Omeros Investigational Site
state: Telangana
city: Chandigarh
country: India
facility: Omeros Investigational Site
city: Bari
country: Italy
facility: Omeros Investigational Site
city: Bergamo
country: Italy
facility: Omeros Investigational Site
city: Eboli
country: Italy
facility: Omeros Investigational Site
city: Messina
country: Italy
facility: Omeros Investigational Site
city: Milano
country: Italy
facility: Omeros Investigational Site
city: Modena
country: Italy
facility: Omeros Investigational Site
city: Parma
country: Italy
facility: Omeros Investigational Site
city: Piacenza
country: Italy
facility: Omeros Investigational Site
city: Seongnam
country: Korea, Republic of
facility: Omeros Investigational Site
state: Geyonggi-do
city: Anyang-si
country: Korea, Republic of
facility: Omeros Investigational Site
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Omeros Investigational Site
city: Incheon
country: Korea, Republic of
facility: Omeros Investigational Site
city: Seoul
country: Korea, Republic of
facility: Omeros Investigational Site
city: Seoul
country: Korea, Republic of
facility: Omeros Investigational Site
city: Seoul
country: Korea, Republic of
facility: Omeros Investigational Site
city: Seoul
country: Korea, Republic of
facility: Omeros Investigational Site
city: Kaunas
country: Lithuania
facility: Omeros Investigational Site
city: Vilnius
country: Lithuania
facility: Omeros Investigational Site
city: Łódź
country: Poland
facility: Omeros Investigational Site
state: Todzi
city: Krakow
country: Poland
facility: Omeros Investigational Site
city: Olsztyn
country: Poland
facility: Omeros Investigational Site
city: Warszawa
country: Poland
facility: Omeros Investigational Site
city: Singapore
country: Singapore
facility: Omeros Investigational Site
city: Singapore
country: Singapore
facility: Omeros Investigational Site
city: Banská Bystrica
country: Slovakia
facility: Omeros Investigational Site
city: Kosice
country: Slovakia
facility: Omeros Investigational Site
city: Madrid
country: Spain
facility: Omeros Investigational Site
state: San Sebastian De Lost Reyes
city: Almeria
country: Spain
facility: Omeros Investigational Site
city: Barcelona
country: Spain
facility: Omeros Investigational Site
city: Cordoba
country: Spain
facility: Omeros Investigational Site
city: Lleida
country: Spain
facility: Omeros Investigational Site
city: Madrid
country: Spain
facility: Omeros Investigational Site
city: Madrid
country: Spain
facility: Omeros Investigational Site
city: Valencia
country: Spain
facility: Omeros Investigational Site
city: Zaragoza
country: Spain
facility: Omeros Investigational Site
city: Stockholm
country: Sweden
facility: Omeros Investigational Site
city: Changhua City
country: Taiwan
facility: Omeros Investigational Site
city: Hualien City
country: Taiwan
facility: Omeros Investigational Site
city: Kaohsiung City
country: Taiwan
facility: Omeros Investigational Site
city: New Taipei City
country: Taiwan
facility: Omeros Investigational Site
city: New Taipei City
country: Taiwan
facility: Omeros Investigational Site
city: Taichung City
country: Taiwan
facility: Omeros Investigational Site
city: Taoyuan City
country: Taiwan
facility: Omeros Investigational Site
city: Bangkok
country: Thailand
facility: Omeros Investigational Site
city: Bangkok
country: Thailand
facility: Omeros Investigational Site
city: Chiang Mai
country: Thailand
facility: Omeros Investigational Site
city: Dusit
country: Thailand
facility: Omeros Investigational Site
city: Khon Kaen
country: Thailand
facility: Omeros Investigational Site
city: Songkla
country: Thailand
facility: Omeros Investigational Site
city: Ankara
country: Turkey
facility: Omeros Investigational Site
city: Bursa
country: Turkey
facility: Omeros Investigational Site
city: Edirne
country: Turkey
facility: Omeros Investigational Site
city: Istanbul
country: Turkey
facility: Omeros Investigational Site
city: Kocaeli
country: Turkey
facility: Omeros Investigational Site
city: Malatya
country: Turkey
facility: Omeros Investigational Site
city: Leicester
country: United Kingdom
facility: Omeros Investigational Site
state: Evington
city: Cambridge
country: United Kingdom
facility: Omeros Investigational Site
city: Cardiff
country: United Kingdom
facility: Omeros Investigational Site
city: Dartford
country: United Kingdom
facility: Omeros Investigational Site
city: London
country: United Kingdom
facility: Omeros Investigational Site
Study officials:
References:
citation: 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.