Resumen

Descripción detallada

Este ensayo evaluará la eficacia, seguridad y tolerabilidad de ianalumab subcutáneo (s.c.) administrado cada 4 semanas (c4s) o cada 12 semanas (c12s) en comparación con placebo, en combinación con el SoC, en participantes adultos con NL activa (glomerulonefritis activa de clase III o IV según ISN/RPS con o sin características coexistentes de clase V, o clase V membranosa pura), utilizando los criterios de la Sociedad Internacional de Nefrología (ISN)/Sociedad de Patología Renal (RPS) de 2003.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 100 YearsSexo: ALL

Criterios de inclusión

Participants eligible for inclusion in this study must meet all of the following criteria:
Adult male and female participants aged 18 years or older at the time of screening
Weigh at least 35 kg at screening
Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria
Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result
Active LN at screening, as defined by meeting the 3 following criteria:

Criterios de exclusión

UPCR ≥ 1.0 g/g on 24h urine collection at Screening
eGFR ≥ 25mL/min/1.73 m2. Participants with eGFR \< 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in ≤ 50% of glomeruli
Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA
Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization
Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications
Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization
Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne.
Able to communicate well with the Investigator to understand and comply with the requirements of the study
Participants meeting any of the following criteria are not eligible for inclusion in this study:
Severe renal impairment as defined by i.) presence of oliguria (defined as a documented urine volume \<400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation
Sclerosis in \> 50% of glomeruli on renal biopsy
Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of certain Traditional Chinese Medicines
Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36 weeks prior to randomization or if therapy was administered \< 36 weeks prior to randomization, B cell count less than the lower limit of normal or patient's own baseline value prior to having received an earlier B cell-depleting therapy
Prior treatment with any of the following within 12 weeks prior to randomization
Belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis
Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors)
Thalidomide treatment and/or methotrexate
Combination of DMARDs
Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA
Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization
History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
Any one of the following laboratory values at screening:
Hemoglobin levels \< 8.0 g/dL (\< 5 mmol/L), or \< 7.0 g/dL (\< 4.3 mmol/L) if related to participant's SLE such as in active hemolytic anaemia
Platelet count \< 25 x 1000/µL
Absolute neutrophil count (ANC) \< 0.8 x 1000/µL
Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients
Receipt of live/attenuated vaccine within a 4-week period prior to randomization
History of primary or secondary immunodeficiency, including a positive HIV test result
History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the participants in case of participation in this study
Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant
Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines)
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping of investigational medication
Sexually active male participants, who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment
Other protocol -defined Inclusion/Exclusion may apply.

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Caba, Buenos Aires, Argentina

WITHDRAWN

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Caba, Argentina

RECRUITING

Novartis Investigative Site

CABA, Argentina

RECRUITING

Novartis Investigative Site

San Miguel de Tucumán, Argentina

RECRUITING

Ensayo multicéntrico de fase 3, aleatorizado, doble ciego, en grupos paralelos, controlado con placebo, para evaluar la eficacia, seguridad y tolerabilidad de ianalumab añadido al tratamiento estándar en participantes con nefritis lúpica activa (SIRIUS-LN).

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

ianalumab s.c. q4w

ianalumab s.c. q12w

placebo s.c.

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals