OMS721 in patients with IgA Nephropathy (ARTEMIS-IGAN)

Phase 1

• Conditions: IgA nephropathy (IgAN); MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2018-000075-33-BG
• Lead Sponsor: Omeros Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-19
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Age 18 years or older at the onset of Screening
• Biopsy confirmed diagnosis of IgAN within 8 years prior to Screening
• Documented history of 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 410
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

• Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), cytotoxic drugs, or eculizumab within 8 weeks prior to Screening, unless such treatment is given for indications other than
IgAN
• Treatment with systemic corticosteroids within 8 weeks prior to screening
• Uncontrolled BP, a systolic BP of > 150 mmHg and a diastolic BP of >100 mmHg at rest despite the combination of two or more antihypertensives including ACE inhibiters, ARBs, or direct renin
inhibitors
• 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 or Run-In
• Presence of significant morbidity or other major illness or disease that may confound the interpretation of the clinical trial results or may result in death within 2 years of Screening
• History of renal transplantation
• Have a known hypersensitivity to any constituent of the investigational product
• Rapidly progressive glomerulonephritis, defined as a fall in eGFR of > 30 mL/min/1.73 m2 within 24 weeks or > 15 mL/min/1.73 m2 within 12 weeks prior to Screening. During the Run-In period a patient will be excluded if they experience a decrease in eGFR of > 15 mL/min/1.73 m2 from their best eGFR from the beginning of Screening.
• Significant abnormalities in clinical laboratory values including any of the following at the time of evaluation during Screening and Run-In:
a. hemoglobin < 9.0 g/dL
b. platelet count < 100,000 cells/mm3
c. absolute neutrophil count < 500 cells/mm3
d. alanine transaminase or aspartate transaminase (AST) > 3.0 × the
upper limit of normal (ULN)
e. serum bilirubin > 2 × ULN
• History of human immunodeficiency virus (HIV), evidence of immune suppression, active hepatitis C virus (HCV) infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), hepatitis B virus (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) or within 5 times the plasma half-life of the administered experimental drug, whichever is longer
• Presence of active infection occurring within 7 days of Screening or at the time of Screening
• Treatment with 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate the effect of OMS721 in patients with IgA nephropathy (IgAN) on proteinuria assessed by 24-hour urine protein excretion (UPE) in g/day at 36 weeks from baseline;Secondary Objective: To evaluate the effect of OMS721 in patients with IgAN on:<br>• Proteinuria assessed by 24-hour UPE at 36 weeks from baseline in the subset of patients with high baseline proteinuria (defined as 24-hour UPE = 2 g)<br>• Durability of proteinuria response from 36 weeks<br>• Renal function as determined by the rate of change in estimated glomerular filtration rate (eGFR) up to 144 weeks from baseline<br>• Safety and tolerability<br>• Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of OMS721;Primary end point(s): - The primary endpoint of this study is the change from baseline in log-transformed 24-hour UPE in g/day at 36 weeks from baseline;Timepoint(s) of evaluation of this end point: 36 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key Secondary Endpoints<br>• Proteinuria responder, defined as having 24 -hour UPE of at least 50% reduction from baseline as assessed at Week 36 (patients with = 2 g/day UPE at baseline only)<br>• The rate of change in eGFR up to 144 weeks from baseline Other Secondary Endpoints<br>• Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 <br>weeks<br>• Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 72 weeks<br>• Time-averaged 24-hour UPE from 36 weeks to 48 weeks to a level at least 50% reduced from the <br>baseline 24-hour UPE (patients with = 2 g/day UPE at baseline only)<br>• Time-averaged 24-hour UPE from 36 weeks to 72 weeks to a level at least 50% reduced from the <br>baseline 24-hour UPE (patients with = 2 g/day UPE at baseline only)<br><br>;Timepoint(s) of evaluation of this end point: 36, 48, and 72 weeks for UPE, and 144 week for the rate of change in eGFR.