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 (ianalumab) or CFZ533 (iscalimab) in patients with systemic lupus erythematosus (SLE) to enable further development of these compounds as treatment in this disease population

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: VAY736; Drug: VAY736 Placebo; Drug: CFZ533; Drug: CFZ533 Placebo

Detailed Description

The study consisted 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 entered 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 entered a Follow-Up period in order to monitor safety and efficacy up to Week 69. The Week 69 visit was the End of Study (EoS) visit for patients in Cohort 2 (CFZ533). Study duration for patients in Cohort 2 was approximately 18 months. For Cohort 1 (VAY736), patients who did not achieve B-cell recovery by Week 69 Visit entered into a Secondary Follow-Up period until achieving B cell recovery criteria (B-cell count was at >= 50 cells/µl or at least 80% of baseline levels). Safety follow-up visits were scheduled as deemed appropriate until the patient achieved the B-cell recovery criteria, followed by an EoS 4 weeks later.

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

Contacts and Locations

Study Locations

• Argentina
  • Caba, 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
  • Prague, Czechia, 128 00
    • Novartis Investigative Site
• France
  • Pessac, France, 33604
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1023
    • Novartis Investigative Site
  • Hajdu Bihar Megye
    • Debrecen, Hajdu Bihar Megye, Hungary, 4032
      • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4578510
      • Novartis Investigative Site
    • Nagoya, Aichi-ken, Japan, 4600001
      • 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, 1608582
      • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Novartis Investigative Site
  • Poznan, Poland, 60-218
    • Novartis Investigative Site
  • Warsaw, Poland, 00-874
    • Novartis Investigative Site
• Russia
  • Moscow, Russia, 115522
    • Novartis Investigative Site
  • Saint Petersburg, Russia, 194044
    • Novartis Investigative Site
  • Yekaterinburg, Russia, 620144
    • Novartis Investigative Site
• South Korea
  • Gwangju, South Korea, 61469
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 407219
    • 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; Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Drug: VAY736; 150 mg powder in vial for solution for injection; after reconstitution to 150 mg/mL per vial, a dose of 300 mg; Other Names: Ianalumab
Placebo Comparator: Cohort 1 VAY736 Placebo; Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49.	Drug: VAY736; 150 mg powder in vial for solution for injection; after reconstitution to 150 mg/mL per vial, a dose of 300 mg; Other Names: Ianalumab; Drug: VAY736 Placebo; solution for injection; 0 mg/mL administered as 2 mL s.c. injection; Other Names: Ianalumab/Placebo
Experimental: Cohort 2 CFZ533; Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (>= 50 kg BW) and 13 mg/kg (< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (>= 50 kg BW) and 13 mg/kg (< 50 kg BW)) until Week 49.	Drug: CFZ533; 150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion; Other Names: Iscalimab
Placebo Comparator: Cohort 2 CFZ533 Placebo; Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (>= 50 kg BW) and 13 mg/kg (< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (>= 50 kg BW) and 13 mg/kg (< 50 kg BW)) until Week 49.	Drug: CFZ533; 150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion; Other Names: Iscalimab; Drug: CFZ533 Placebo; Placebo as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion; Other Names: Iscalimab/Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29	The primary endpoint was a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders. SRI-4 response is defined as below: having >= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND; no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND; <10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline Sustained reduction in oral corticosteroid is defined as below: =< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND; no increase of that dose from Week 17 through Week 29	Baseline, Week 17 to Week 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity	The Physician's global assessment (PhGA-VAS) of disease activity was performed using 100 mm VAS ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.	Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity	The patient's global assessment of disease activity was performed using a Visual Analogue Scale (VAS) of 100 mm ranging from "no disease activity" (score 0) to "severe disease activity" (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.	Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Percentage of Participants With Flare	Flare was defined as one new 'A' score or two or more 'B' scores using the British Isles Lupus Assessment Group Index (BILAG -2004).	Up to 69 weeks
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	Up to 69 weeks
Pharmacokinetics (PK) Cohort 1 - VAY736 Free Serum Concentration	Note: End of study (EoS) was a floating timepoint and did not represent a uniform timepoint across the study.	Weeks 29, 53, 69, and EoS (up to 69 weeks), pre-dose
PK Cohort 2 - Free CFZ533 Concentration in Plasma		Weeks 29, 53, and 69, pre-dose
PD Cohort 2 (CFZ533): Total Soluble CD40		Weeks 29, 53, and 69
Percentage of Participants With Anti-drug Antibodies (ADAs)	ADAs were measured in plasma for CFZ533 and in serum for VAY736. Note: End of study (EoS) was a floating timepoint and did not represent a uniform timepoint across the study.	Baseline, Weeks 29, 53, 69, and EoS (up to 69 weeks)

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 (Actual): April 28, 2025

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): May 14, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

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: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Substandard Drugs; Pharmaceutical Preparations; ianalumab; iscalimab
• 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