Resumen

El propósito de este estudio es evaluar la eficacia, la seguridad y la tolerabilidad de ianalumab administrado por vía subcutánea (s.c.) en participantes con esclerosis sistémica cutánea difusa en comparación con placebo.

Descripción detallada

El estudio comprende los siguientes períodos: * Período de selección (screening), con una duración de hasta 6 semanas; * Período de tratamiento 1, con una duración de 52 semanas; * Período de tratamiento 2 (tratamiento abierto), con una duración de 52 semanas; * Período de seguimiento postratamiento, con una duración de al menos 20 semanas tras la última dosis y hasta 2 años.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 70 YearsSexo: ALL

Criterios de inclusión

Male and female participants \>= 18 and =\< 70 years (at the time of the screening visit).
Diagnosis of systemic sclerosis, as defined by the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria for SSc (van den Hoogen et al 2013) and meet the dcSSc subset classification according to LeRoy (LeRoy 1988)
Disease duration of =\< 60 months (defined as time from the first non-Raynaud phenomenon manifestation, e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea)
mRSS units of \>= 15 and =\< 45 at the time of the screening visit
Active disease that meets at least one of the following criteria at screening:
Disease duration of =\< 18 months defined as time from the first non-Raynaud phenomenon manifestation
Increase in mRSS of \>= 3 units compared with the most recent assessment performed within the previous 6 months
Involvement of one new body area and an increase in mRSS of \>= 2 units compared with the most recent assessment performed within the previous 6 months
Involvement of two new body areas within the previous 6 months
Elevated acute phase reactants (ESR) \>= 30 mm/hr or high-sensitivity C-reactive protein (hsCRP) \>= 6 mg/L)
Presence of SSc-interstitial lung disease (ILD) and ATA autoantibody positivity
Modified EUSTAR disease activity index (mDAI) ≥ 2.5
Participant must be positive for at least one of the following autoantibodies:
anti-topoisomerase I (ATA) (also known as anti-SCL-70)
anti-RNA polymerase III (anti-RNAP3)
anti-nuclear antibody (ANA) (≥ 1:80) Participants who are positive only for ANA (while being negative for both ATA /anti-RNAP3) will be limited to 30% of the overall randomized study population.
Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit.
Use of anti-fibrotic agents including colchicine, D-penicillamine, pirfenidone, or tyrosine kinase inhibitors (e.g., nintedanib, nilotinib, imatinib, dasatinib) in the 4 weeks prior to baseline visit. Patients with SSc-ILD requiring antifibrotics for management of ILD during the study, as per investigator judgement, should be excluded.
Previous treatment with chlorambucil, bone marrow transplantation or total lymphoid irradiation.
Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception (failure rate \< 1% per year) while taking study treatment and for 6 months after stopping study treatment.

Criterios de exclusión

Rheumatic disease other than dcSSc, including limited cutaneous disease (lcSSc) or sine scleroderma at the screening visit. Secondary Sjogren's disease and scleroderma myopathy are not exclusionary.
Positive anti-centromere antibody (ACA+) without positive ATA or anti-RNAP3 autoantibody result at the screening visit
Previous improvement (decrease) in mRSS \> 10 units
Pulmonary disease with FVC ≤ 50% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO, corrected for hemoglobin) ≤ 40% of predicted at the screening visit
WHO Functional Class 3 or higher assessment for pulmonary arterial hypertension (PAH, as defined on right heart catheterization), receiving IV therapy for PAH or evidence of other moderately severe pulmonary disease
Participants treated with cyclophosphamide within 12 weeks prior to Baseline.
Prior use of a B-cell depleting therapy other than ianalumab (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) administered within 36 weeks prior to randomization, or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower).

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

CABA, 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

Estudio multicéntrico aleatorizado, doble ciego, de grupos paralelos, controlado con placebo, para evaluar la eficacia, la seguridad y la tolerabilidad de ianalumab en participantes con esclerosis sistémica cutánea difusa

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

Ianalumab

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals