Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT03656562
• Date of registration: 19/07/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients
• Scientific title: 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)
• Date of first enrolment: December 19, 2018
• Target sample size: 107
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03656562
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, China, Czechia, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Thailand, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

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

- 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus (SLE)

Intervention(s)

Drug: CFZ533 Placebo

Drug: CFZ533

Drug: VAY736

Drug: VAY736 Placebo

Primary Outcome(s)

SRI-4 response status [Time Frame: 29 Weeks]

Secondary Outcome(s)

PK Cohort 1 - Cmax,ss [Time Frame: 18+ months]

PK Cohort 2 - Cmax,ss [Time Frame: 18 months]

PGA VAS - global disease activity [Time Frame: from baseline to Week 29]

PhGA VAS - overall disease activity [Time Frame: from Baseline to Week 29]

PK Cohort 1 - Ctrough,ss [Time Frame: 18+ months]

PK Cohort 2 - Ctrough,ss [Time Frame: 18 months]

Flare rate and time to first flare [Time Frame: 18 months]

PD Cohort 2 (CFZ533): total soluble CD40 [Time Frame: 18 months]

Time to first flare [Time Frame: 18 months]

Secondary ID(s)

2018-001508-12

CVAY736X2208

Source(s) of Monetary Support

Please refer to primary and secondary sponsors