Resumen

This study is designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of treatment with either VAY736 (ianalumab) or CFZ533 (iscalimab) in patients with systemic lupus erythematosus (SLE) to enable further development of these compounds as treatment in this disease population

Descripción detallada

The study consists of a 28-day screening period, a blinded treatment period of 28 weeks where randomized patients received treatment with investigational drug (ianalumab or iscalimab) or placebo. At the end of Week 29 visit, the patients enter the open label treatment phase where patients in active treatment group continued to receive active treatment and patients in placebo group started active treatment with ianalumab/iscalimab until Week 49. After completion of the open-label treatment period, all patients enter a Follow-Up period in order to monitor safety and efficacy up to Week 69. The Week 69 visit is the End of Study (EoS) visit for patients in Cohort 2 (CFZ533). Study duration for patients in Cohort 2 will be approximately 18 months. For Cohort 1 (VAY736). Patients who do not achieve B-cell recovery by Week 69 Visit will enter into a Secondary Follow-Up period until achieving B cell recovery criteria (B-cell count is at \>= 50 cells/µl or at least 80% of baseline levels). Safety follow-up visits will be scheduled as deemed appropriate until the patient achieves the B cell recovery criteria, followed by an EoS 4 weeks later.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Written informed consent must be obtained before any assessment is performed
Fulfill ≥4 of the 11 American College of Rheumatology 1997 classification criteria for SLE
Patient diagnosed with SLE for at least 6 months prior to screening
Elevated serum titers at screening of ANA (≥1:80) of a pattern consistent with an SLE diagnosis, including at a minimum either anti-double stranded DNA (anti-ds DNA) or anti-Ro (SSA) or anti-La (SSB) or anti-nuclear ribonucleoprotein (anti-RNP) or anti-Smith (anti-Sm)
Currently receiving corticosteroids and/or anti-malarial and/or thalidomide treatment and/or another DMARD on a stable dose according to protocol requirements
SLEDAI-2K score of ≥6 at screening
BILAG 2004 score of one "A" score either in the mucocutaneous or in the musculoskeletal domain or one "B" score in either the mucocutaneous or musculoskeletal domain and at least one "A" or "B" score in a second domain at screening
Weigh at least 40 kg at screening

Criterios de exclusión

Cohort 2 (CFZ533/Placebo) only:
Patients who are at significant risk for thromboembolic events based on the following:
History of either thrombosis or 3 or more spontaneous abortions
Presence of lupus anticoagulant or significantly prolonged activated partial thromboplastin time (aPTT) consistent with co-existent anti-phospholipid syndrome and without concurrent prophylactic treatment with aspirin or anticoagulants as per local standard of care
All Cohorts:
History of receiving prior to screening:
Within 12 weeks: i.v. corticosteroids, calcineurin inhibitors or other oral DMARD
Within 24 weeks: cyclophosphamide or biologics such as intravenous Ig, plasmapheresis, anti-TNF-a mAb, CTLA4-Fc Ig (abatacept) or BAFF targeting agents (e.g., belimumab)
Any B-cell depleting therapies (e.g., anti-CD20 mAb, anti-CD22 mAb, anti-CD52 mAb) or TACI-Ig (atacicept) administered within 52 weeks prior to screening, and a B-cell count \<50 cells/μ at the time of screening
Evidence of past exposure to tuberculosis as assessed by Quantiferon testing at screening
Presence of human immunodeficiency virus (HIV) infection at screening
Severe organ dysfunction or life threatening disease; ECOG performance status \> 1 at screening
Presence of WHO Class III-IV renal involvement with proliferative disease Presence of severe lupus kidney disease as defined by proteinuria above 6 g/day or equivalent using spot urine protein creatinine ratio, or serum creatinine greater than 2.5 mg/dL (221.05 μmol/L), or requiring immune suppressive induction or maintenance treatment exceeding protocol defined limits
Active viral, bacterial or other infections at the time of screening or enrollment
Receipt of live/attenuated vaccine within a 2-month period before first dosing
Uncontrolled, co-existing serious disease, e.g., uncontrolled hypertension, heart failure, type I diabetes, thyroid disease within 3 months prior to first dosing, or significant, unresolved illness within 2 weeks prior to first dosing
History of hypersensitivity to drugs of similar chemical class
Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Subjects who are HBsAg negative and HBcAb positive are excluded unless negative for HBV DNA. Once past screening and enrolled into study, requirements for monitoring and antiviral treatment are enacted.
Subjects with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded.

Intervenciones

drug

VAY736

150 mg powder in vial for solution for injection; after reconstitution to 150 mg/mL per vial, a dose of 300 mg

drug

VAY736 Placebo

solution for injection; 0 mg/mL administered as 2 mL s.c. injection

drug

CFZ533

150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion

drug

CFZ533 Placebo

Placebo as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion

A Placebo-controlled, Patient and Investigator Blinded, Randomized Parallel Cohort Study to Assess Pharmacodynamics, Pharmacokinetics, Safety, Tolerability and Preliminary Clinical Efficacy of VAY736 and CFZ533 in Patients With Systemic Lupus Erythematosus (SLE)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

VAY736

VAY736 Placebo

CFZ533

CFZ533 Placebo

Ubicaciones

Novartis Investigative Site

Patrocinadores