Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy
- Conditions
- IgA Nephropathy
- Interventions
- Biological: OMS721Other: Vehicle (D5W or saline)
- Registration Number
- NCT03608033
- Lead Sponsor
- Omeros Corporation
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 356
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OMS721 OMS721 Administration of OMS721 Placebo Vehicle (D5W or saline) Administration of Vehicle (D5W or Saline Solution)
- Primary Outcome Measures
Name Time Method Change from baseline in 24-hour UPE in IgA nephropathy (IgAN) patients assessed at 36 weeks from baseline 36 Weeks
- Secondary Outcome Measures
Name Time Method Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 and 72 weeks 36 and 72 Weeks Pharmacokinetics of narsoplimab intravenous infusion Week 12 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
Assessment of pharmacodynamics of narsoplimab intravenous infusion with presence of positive anti-drug antibodies Week 12 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.
Assessment of percentage of participants with presence of neutralizing antibodies Week 12 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.
Safety and tolerability of narsoplimab for the treatment of IgAN Week 112 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
Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks 36 and 48 Weeks Renal function as determined by the rate of change in eGFR at up to 96 weeks from baseline. 96 Weeks Assessment of pharmacokinetics of narsoplimab intravenous infusion Week 12 By evaluating the area under the concentration-time curve from dosing time (AUC) at baseline and study days, T1, T4, T8, T10,T12
Change from baseline in log-transformed 24-hour uPCR through 36 weeks. Week 36 Assessment of pharmacodynamics of narsoplimab intravenous infusion 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 Weeks 1, T4 Week 2-11, T8 Week 2-11, T10 Week 2-11, T12 Week 12 ±2 days
Trial Locations
- Locations (2)
Omeros Investigational Site
🇬🇧London, United Kingdom
Omeros Investigation Sites
🇺🇸Phoenix, Arizona, United States