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

IgA Nephropathy Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03608033
• Other study ID #: OMS721-IGA-001
• Status: Terminated
• Phase: Phase 3
• Start date: February 16, 2018
• Est. completion date: October 18, 2023

Study information

• Verified date: March 2024
• Source: Omeros Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 356
• Est. completion date: October 18, 2023
• Est. primary completion date: October 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Biological:
• OMS721
Biological: OMS721

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

Locations

Country	Name	City	State
Argentina	Omeros Investigational Site	Buenos Aires
Argentina	Omeros Investigational Site	Cordoba
Argentina	Omeros Investigational Site	Posadas	Misiones
Argentina	Omeros Investigational Site	Salta
Australia	Omeros Investigational Site	Adelaide	South Australia
Australia	Omeros Investigational Site	Clayton	Victoria
Australia	Omeros Investigational Site	Footscray	Saint Albans
Australia	Omeros Investigational Site	Garran	Australian Capital Territory, Woden
Belgium	Omeros Investigational Site	Gent
Belgium	Omeros Investigational Site	Leuven
Belgium	Omeros Investigational Site	Liège
Bulgaria	Omeros Investigational Site	Plovdiv
Bulgaria	Omeros Investigational Site	Plovdiv
Bulgaria	Omeros Investigational Site	Sofia
Canada	Omeros Investigational Site	London	Ontario
Canada	Omeros Investigational Site	Toronto	Ontario
Canada	Omeros Investigational Site	Vancouver	British Columbia
Canada	Omeros Investigational Site	Vancouver	British Columbia
Czechia	Omeros Investigational Site	Prague	Praha
Germany	Omeros Investigational Site	Aachen	Nordrhein-Westfalen
Germany	Omeros Investigational Site	Göttingen
Germany	Omeros Investigational Site	Mannheim	Baden-Wrttemberg
Germany	Omeros Investigational Site	München	Bayern
Germany	Omeros Investigational Site	Villingen-Schwenningen
Greece	Omeros Investigational Site	Athens
Greece	Omeros Investigational Site	Heraklion
Greece	Omeros Investigational Site	Iraklio
Greece	Omeros Investigational Site	Patra
Greece	Omeros Investigational Site	Thessaloniki	Pilea-Chortiatis
Hungary	Omeros Investigational Site	Baja
Hungary	Omeros Investigational Site	Budapest
Hungary	Omeros Investigational Site	Gyor
Hungary	Omeros Investigational Site	Pecs
Hungary	Omeros Investigational Site	Szeged
India	Omeros Investigational Site	Belagam	Karnataka
India	Omeros Investigational Site	Chandigarh
India	Omeros Investigational Site	Hyderabad	Telangana
India	Omeros Investigational Site	Hyderabad	Telangana
India	Omeros Investigational Site	Hyderabad	Telangana
India	Omeros Investigational Site	Hyderabad	Ameerpet
India	Omeros Investigational Site	Jaipur	Rajasthan
India	Omeros Investigational Site	Kozhikode	Kerala
India	Omeros Investigational Site	Mangalore	Karnataka
India	Omeros Investigational Site	Nadiad	Gujarat
India	Omeros Investigational Site	New Delhi	New India
Italy	Omeros Investigational Site	Bari
Italy	Omeros Investigational Site	Bergamo
Italy	Omeros Investigational Site	Eboli
Italy	Omeros Investigational Site	Messina
Italy	Omeros Investigational Site	Milano
Italy	Omeros Investigational Site	Modena
Italy	Omeros Investigational Site	Parma
Italy	Omeros Investigational Site	Piacenza
Korea, Republic of	Omeros Investigational Site	Anyang-si	Gyeonggi-do
Korea, Republic of	Omeros Investigational Site	Busan
Korea, Republic of	Omeros Investigational Site	Incheon
Korea, Republic of	Omeros Investigational Site	Seongnam	Geyonggi-do
Korea, Republic of	Omeros Investigational Site	Seoul
Korea, Republic of	Omeros Investigational Site	Seoul
Korea, Republic of	Omeros Investigational Site	Seoul
Korea, Republic of	Omeros Investigational Site	Seoul
Lithuania	Omeros Investigational Site	Kaunas
Lithuania	Omeros Investigational Site	Vilnius
Poland	Omeros Investigational Site	Krakow
Poland	Omeros Investigational Site	Lódz	Todzi
Poland	Omeros Investigational Site	Olsztyn
Poland	Omeros Investigational Site	Warszawa
Singapore	Omeros Investigational Site	Singapore
Singapore	Omeros Investigational Site	Singapore
Slovakia	Omeros Investigational Site	Banská Bystrica
Slovakia	Omeros Investigational Site	Kosice
Spain	Omeros Investigational Site	Almeria
Spain	Omeros Investigational Site	Barcelona
Spain	Omeros Investigational Site	Cordoba
Spain	Omeros Investigational Site	Lleida
Spain	Omeros Investigational Site	Madrid
Spain	Omeros Investigational Site	Madrid
Spain	Omeros Investigational Site	Madrid	San Sebastian De Lost Reyes
Spain	Omeros Investigational Site	Valencia
Spain	Omeros Investigational Site	Zaragoza
Sweden	Omeros Investigational Site	Stockholm
Taiwan	Omeros Investigational Site	Changhua City
Taiwan	Omeros Investigational Site	Hualien City
Taiwan	Omeros Investigational Site	Kaohsiung City
Taiwan	Omeros Investigational Site	New Taipei City
Taiwan	Omeros Investigational Site	New Taipei City
Taiwan	Omeros Investigational Site	Taichung City
Taiwan	Omeros Investigational Site	Taoyuan City
Thailand	Omeros Investigational Site	Bangkok
Thailand	Omeros Investigational Site	Bangkok
Thailand	Omeros Investigational Site	Chiang Mai
Thailand	Omeros Investigational Site	Dusit
Thailand	Omeros Investigational Site	Khon Kaen
Thailand	Omeros Investigational Site	Songkla
Turkey	Omeros Investigational Site	Ankara
Turkey	Omeros Investigational Site	Bursa
Turkey	Omeros Investigational Site	Edirne
Turkey	Omeros Investigational Site	Istanbul
Turkey	Omeros Investigational Site	Kocaeli
Turkey	Omeros Investigational Site	Malatya
United Kingdom	Omeros Investigational Site	Cambridge
United Kingdom	Omeros Investigational Site	Cardiff
United Kingdom	Omeros Investigational Site	Dartford
United Kingdom	Omeros Investigational Site	Leicester	Evington
United Kingdom	Omeros Investigational Site	London
United States	Omeros Investigational Site	Amarillo	Texas
United States	Omeros Investigational Site	Boston	Massachusetts
United States	Omeros Investigational Site	Charleston	South Carolina
United States	Omeros Investigational Site	Chattanooga	Tennessee
United States	Omeros Investigational Site	Chicago	Illinois
United States	Omeros Investigational Site	Cincinnati	Ohio
United States	Omeros Investigational Site	Columbus	Ohio
United States	Omeros Investigational Site	Dallas	Texas
United States	Omeros Investigational Site	Denver	Colorado
United States	Omeros Investigational Site	Florence	Alabama
United States	Omeros Investigational Site	Fresh Meadows	New York
United States	Omeros Investigational Site	Houston	Texas
United States	Omeros Investigational Site	Iowa City	Iowa
United States	Omeros Investigational Site	Lawrenceville	Georgia
United States	Omeros Investigational Site	Los Angeles	California
United States	Omeros Investigational Site	Los Angeles	California
United States	Omeros Investigational Site	Mesa	Arizona
United States	Omeros Investigational Site	Miami	Florida
United States	Omeros Investigational Site	Miami Lakes	Florida
United States	Omeros Investigational Site	Milwaukee	Wisconsin
United States	Omeros Investigational Site	Minneapolis	Minnesota
United States	Omeros Investigational Site	New York	New York
United States	Omeros Investigational Site	Northridge	California
United States	Omeros Investigational Site	Philadelphia	Pennsylvania
United States	Omeros Investigation Sites	Phoenix	Arizona
United States	Omeros Investigational Site	Rochester	Minnesota
United States	Omeros Investigational Site	Saint Louis	Missouri
United States	Omeros Investigational Site	San Dimas	California
United States	Omeros Investigational Site	San Francisco	California
United States	Omeros Investigational Site	Scottsdale	Arizona
United States	Omeros Investigational Site	Scottsdale	Arizona
United States	Omeros Investigational Site	Springfield	Massachusetts
United States	Omeros Investigational Site	Stanford	California
United States	Omeros Investigational Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Omeros Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Germany,  Greece,  Hungary,  India,  Italy,  Korea, Republic of,  Lithuania,  Poland,  Singapore,  Slovakia,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in 24-hour UPE in IgA nephropathy (IgAN) patients assessed at 36 weeks from baseline		36 Weeks
Secondary	Renal function as determined by the rate of change in eGFR at up to 96 weeks from baseline.		96 Weeks
Secondary	Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks		36 and 48 Weeks
Secondary	Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 and 72 weeks		36 and 72 Weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in log-transformed 24-hour uPCR through 36 weeks.		Week 36