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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: VAY736; Drug: VAY736 Placebo; Drug: CFZ533; Drug: CFZ533 Placebo

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
      • Novartis Investigative Site
• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
• China
  • Shanghai, China, 200127
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Novartis Investigative Site
• Czechia
  • Praha 2, Czechia, 128 50
    • Novartis Investigative Site
• France
  • Pessac Cedex, France, 33604
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1023
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • Novartis Investigative Site
    • Nagoya, Aichi, Japan, 457 8510
      • Novartis Investigative Site
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104-8560
      • Novartis Investigative Site
    • Shinjuku ku, Tokyo, Japan, 162 8655
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160 8582
      • Novartis Investigative Site
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85 168
    • Novartis Investigative Site
  • Poznan, Poland, 60-218
    • Novartis Investigative Site
  • Warszawa, Poland, 00-874
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
  • Yekaterinburg, Russian Federation, 620109
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 40705
    • Novartis Investigative Site
  • Taiwan ROC
    • Taichung, Taiwan ROC, Taiwan, 40201
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 VAY736; multiple doses of VAY736, s.c.	Drug: VAY736; Powder for solution for injection
Placebo Comparator: Cohort 1 VAY736 Placebo; multiple doses of matching placebo s.c. until week 29. Multiple doses of VAY736, s.c from week 29 until week 53.	Drug: VAY736 Placebo; Solution for injection
Experimental: Cohort 2 CFZ533; multiple doses of CFZ533, i.v.	Drug: CFZ533; Concentrate for solution for infusion
Placebo Comparator: Cohort 2 CFZ533 Placebo; multiple doses of matching placebo i.v. until week 29. Multiple doses of CFZ533, i.v. from week 29 until week 53.	Drug: CFZ533 Placebo; Solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRI-4 response status	SRI-4 response status at Week 29 (reduced steroid dose maintained between Weeks 17 and 29). Clinical efficacy will be measured using the SLE Responder Index (SRI-4), a composite endpoint that incorporates SLEDAI-2K, BILAG 2004, and a visual analog scale (VAS) of physician-rated disease activity to determine patient improvement.	29 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PhGA VAS - overall disease activity	Changes between baseline and Week 29 in the Physicians' Global Assessment (PhGA) visual analog scale (VAS) assessing patient's overall disease activity	from Baseline to Week 29
PGA VAS - global disease activity	Changes between baseline and Week 29 in the Patient's Global Assessment (PGA) visual analog scale (VAS) assessing patient's global disease activity	from baseline to Week 29
Flare rate and time to first flare	Flare rate and time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004	18 months
Time to first flare	Time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004	18 months
PK Cohort 1 - Cmax,ss	PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)	18+ months
PK Cohort 1 - Ctrough,ss	PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)	18+ months
PK Cohort 2 - Cmax,ss	PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).	18 months
PK Cohort 2 - Ctrough,ss	PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).	18 months
PD Cohort 2 (CFZ533): total soluble CD40	PD Cohort 2 (CFZ533): total soluble CD40 in plasma.	18 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): July 27, 2022
• Study Completion (Estimated): April 24, 2026

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: SLE; Systemic Lupus Erythematosus; VAY736; B-cell depletion; CFZ533; iscalimab; Anti-CD40; anti-BAFF-receptor; BAFF-receptor blockade; ianalumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CVAY736X2208; 2018-001508-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No