Resumen

El estudio está diseñado como un ensayo multicéntrico, aleatorizado, doble ciego y controlado con placebo para demostrar la superioridad de iptacopan (LNP023) a una dosis de 200 mg dos veces al día en comparación con placebo sumado al tratamiento máximo tolerado con IECAs o ARAs en la reducción de la proteinuria y el enlentecimiento de la progresión de la enfermedad renal en pacientes con nefropatía por IgA primaria.

Descripción detallada

El propósito del estudio es evaluar la eficacia y seguridad de iptacopan (LNP023) en comparación con placebo en la reducción de la proteinuria y el enlentecimiento de la progresión de la enfermedad en pacientes con nefropatía por IgA primaria. El estudio constituirá el ensayo pivotal para el registro de LNP023 en pacientes con nefropatía por IgA, con el objetivo de demostrar una reducción clínicamente significativa de la proteinuria con LNP023 frente a placebo, evaluada mediante la reducción del cociente proteína/creatinina en orina (UPCR) de una recolección de orina de 24 horas en un análisis intermedio a los 9 meses. El ensayo continuará de forma enmascarada para confirmar la eficacia a largo plazo basada en la pendiente total anualizada del descenso de la eGFR durante 24 meses, a fin de aportar evidencia confirmatoria de la eficacia y seguridad de LNP023 en el tratamiento de pacientes con nefropatía por IgA. El ensayo enrolará aproximadamente 470 participantes: 430 participantes con nefropatía por IgA confirmada por biopsia y eGFR ≥30 mL/min/1,73 m² (población principal del estudio) y hasta aproximadamente 40 participantes con eGFR de 20 a <30 mL/min/1,73 m² (población con insuficiencia renal grave).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 100 YearsSexo: ALL

Criterios de inclusión

Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmed IgA nephropathy as follows:
For patients eGFR\* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required.
For patients with eGFR\* 30 to \<45ml/min/1.73m2, a qualifying biopsy performed within 2 years with \< 50% tubulointerstitial fibrosis is required.
For patients with eGFR\* 20 to \<30ml/min/1.73m2, a qualifying biopsy performed at any time.
In all cases, if a historical biopsy is not available, one may be performed during screening. \*eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)
Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
If not previously vaccinated, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration.
All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for approximately 90 days before first study drug administration. In addition, if patients are taking diuretics, other antihypertensive medication, or other background medication for IgAN, the doses should also be stabilized for approximately 90 days prior to the first dosing of study treatment.

Criterios de exclusión

Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
Sitting office SBP \>140 mmHg or DBP \>90 mmHg at the randomization visit
Patients previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (\>7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration. Participants previously or currently treated with oral budesonide. Participants treated with endothelin (receptor) antagonists within 90 days prior to first study drug administration.
Prior use of iptacopan (LNP023) or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo
History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.

Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos y fase III para evaluar la eficacia y seguridad de LNP023 en pacientes con nefropatía por IgA primaria

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

LNP023

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores