Resumen

Este estudio está diseñado como un estudio multicéntrico, aleatorizado, doble ciego, de grupos paralelos y controlado con placebo para evaluar la eficacia y seguridad de iptacopan (LNP023) en la glomerulonefritis membranoproliferativa idiopática mediada por complejos inmunes.

Descripción detallada

El propósito de este estudio de fase III es evaluar la eficacia y seguridad de iptacopan en comparación con placebo (ambos administrados en combinación con el tratamiento estándar) en participantes (adultos y adolescentes de 12 a 17 años) con IC-MPGN idiopática. El estudio tiene como objetivo demostrar una reducción de la proteinuria y una mejoría en la tasa de filtración glomerular estimada (TFGe) en los participantes tratados con iptacopan en comparación con placebo. También se evaluará el cambio en la fatiga reportada por el paciente. Se cree que la desregulación de la vía alternativa del complemento (VAlC) subyace a las manifestaciones clínicas y la progresión de la IC-MPGN. Al completar el tratamiento del estudio, los participantes tendrán la opción de interrumpir el tratamiento con iptacopan e ingresar a un seguimiento de seguridad de 30 días, o continuar el tratamiento con iptacopan mediante la transición a un estudio de extensión abierta (CLNP023B12001B; NCT03955445) y proseguir el tratamiento con iptacopan.

Elegibilidad

Edad mínima: 12 YearsEdad máxima: 60 YearsSexo: ALL

Criterios de inclusión

Male and female patients including adults (aged at least 18 years to ≤ 60 years) and adolescents (12 -17 years in non-EU countries at screening and 16-17 years in EU countries at screening).
Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only).
Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin angiotensin system inhibitors (RASi), e.g an ACEi or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization
UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15
Estimated GFR (using the chronic kidney disease \[CKD\]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.
Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care.
If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration.

Criterios de exclusión

Systemic lupus erythematosus (SLE)
Sjögren syndrome
Rheumatoid arthritis
Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
Fibrillary glomerulonephritis
Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy.
Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%.
Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae.
The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 3 months or 5 half-lives prior to the Screening visit.
The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose \>7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration.
The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement.
Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator.
Body mass index (BMI) \>38 kg/m2 at screening and randomization. Body weight \<35 kg at screening and randomization
Participants who have undergone cell or solid organ transplantation, including kidney transplantation.
Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions:
Deposition of antigen-antibody immune complexes as a result of any chronic infections, including
Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV);
Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections
Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis
Renal deposition of immune complexes as a result of a systemic autoimmune disease:

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

CABA, Argentina

RECRUITING

Novartis Investigative Site

Santa Fe, Argentina

RECRUITING

Un estudio multicéntrico, aleatorizado, doble ciego, de grupos paralelos y controlado con placebo para evaluar la eficacia y seguridad de iptacopan (LNP023) en la glomerulonefritis membranoproliferativa idiopática mediada por complejos inmunes (IC-MPGN).

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

iptacopan

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals