Systemic lupus erythematosus (SLE) MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent must be obtained before any assessment is performed - Male and female patients 18 to 75 years of age - 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 antimalarial 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 at screening of: ?-- at least one "A" in either the mucocutaneous domain or in the musculoskeletal domain, OR ?-- one "B" in either the mucocutaneous or musculoskeletal domain AND at least one "A" or "B" in a second domain - Weigh at least 40 kg at screening - Other protocol-defined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 115 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 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 - Severe organ dysfunction or life threatening 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 2month 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. - Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the effect of VAY736 and of CFZ533 versus their respective placebo on disease activity in SLE patients using the SRI-4 index.;Secondary Objective: - To assess safety and tolerability in patients with SLE by recording all adverse events - To determine the change from baseline in the Physicians’ Global Assessment (PhGA) at Week 29 by using a visual analogue scale (VAS) - To determine the change from baseline in the Patient's Global Assessment (PGA) at Week 29 by using a patients VAS - To determine the pharmacokinetics (PK) of multiple doses of VAY736 (s.c.) and CFZ533 (i.v.) in SLE patients by analyzing PK concentrations in blood - To assess the effect of VAY736 and of CFZ533 versus their respective placebo to prevent disease flares in SLE patient’s using BILAG-2004 - To evaluate the immunogenicity of multiple doses of VAY736 (s.c.) or CFZ533 (i.v.) in SLE patients by analyzing anti-drug antibodies in blood - To evaluate the pharmacodynamics (PD; rate, extent and duration of target engagement) of multiple doses of CFZ533 in SLE patients by analyzing total soluble CD40 in plasma;Primary end point(s): SRI-4 response status at Week 29 with reduced steroid dose maintained between Weeks 17 and 29;Timepoint(s) of evaluation of this end point: 29 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes between baseline and Week 29 in the PhGA visual analog scale (VAS) assessing patient’s overall disease activity - Changes between baseline and Week 29 in the PGA visual analog scale (VAS) assessing patient’s global disease activity - Flare rate and time to first flare, with flare defined as one new ‘A’ score or two or more ‘B’ score using BILAG-2004 - Time to first flare, with flare defined as one new ‘A’ score or two or more ‘B’ score using BILAG -2004 - PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state) - PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state) - PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state). - PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state). - PD Cohort 2 (CFZ533): total soluble CD40 in plasma.;Timepoint(s) of evaluation of this end point: 29 Weeks 29 Weeks 18 months 18 months End of Study End of Study 18 months 18 months 18 months | — |
Countries
Argentina, Australia, China, Czechia, Czech Republic, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Thailand, United States
Contacts
Public ContactInformacní služba – klin. hodnocení
Novartis s.r.o.
Outcome results
None listed