Resumen

El objetivo primario de este estudio es evaluar el efecto de OMS721 sobre la excreción urinaria de proteínas (EUP) en 24 horas en pacientes con nefropatía IgA (NIgA) con proteinuria basal elevada (grupo de proteinuria de alto riesgo; EUP en 24 h ≥2 g/día) evaluada a las 36 semanas desde el inicio.

Descripción detallada

Este es un estudio de fase 3, doble ciego, aleatorizado, controlado con placebo, en pacientes de 18 años o más con diagnóstico de NIgA confirmado por biopsia y EUP en 24 horas >1 g/día. El propósito de este estudio es evaluar la eficacia y la seguridad de narsoplimab (OMS721) en comparación con placebo sobre la proteinuria, y determinar si narsoplimab tiene la capacidad de enlentecer la progresión de la enfermedad en pacientes con NIgA primaria. El objetivo primario del estudio es evaluar la reducción de la proteinuria medida mediante EUP en 24 horas a las 36 semanas desde el inicio. El ensayo continuará más allá de las 36 semanas de forma enmascarada para aportar evidencia confirmatoria de eficacia a largo plazo basada en la pendiente anualizada de la TFGe durante 24 meses. El ensayo inscribirá aproximadamente 450 pacientes, 225 por brazo, todos con NIgA confirmada por biopsia, TFGe ≥30 mL/min/1,73 m² y EUP en 24 horas >1 g/día. La duración del estudio para cada paciente se estima en aproximadamente 112 semanas.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Age 18 years or older at the onset of Screening
Biopsy confirmed diagnosis of IgAN within 8 years prior to Screening or Run-in Visit 1
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

Criterios de exclusión

Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), Chinese traditional medicine with immunosuppressive function, cytotoxic drugs, or eculizumab within 8 weeks prior to Screening, unless such treatment is given for indications other than IgA.
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 anti-hypertensives including ACE inhibitors, 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. 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
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 m\^2 within 24 weeks or \> 15 mL/min/1.73 m\^2 within 12 weeks prior to Screening
Significant abnormalities in clinical laboratory values
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
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

Estudio de Fase 3, Aleatorizado, Doble Ciego, Controlado con Placebo, sobre la Seguridad y la Eficacia de OMS721 en Pacientes con Nefropatía por Inmunoglobulina A (IgA) (ARTEMIS - IGAN)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

OMS721

Vehicle (D5W or saline)

Ubicaciones

Omeros Investigational Site

Omeros Investigational Site

Omeros Investigational Site

Omeros Investigational Site

Patrocinadores