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

NCT ID: NCT03656562

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-19
• Study Completion Date: 2025-04-28

Brief Summary

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

Detailed Description

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.

Conditions

Systemic Lupus Erythematosus (SLE)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

VAY736

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

VAY736

Intervention Type: DRUG

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

VAY736 Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

CFZ533

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

CFZ533

Intervention Type: DRUG

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

CFZ533 Placebo

Intervention Type: DRUG

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

Interventions

VAY736

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

Intervention Type: DRUG

VAY736 Placebo

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

Intervention Type: DRUG

CFZ533

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

Intervention Type: DRUG

CFZ533 Placebo

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

Intervention Type: DRUG

Other Intervention Names

Ianalumab; Ianalumab/Placebo; Iscalimab; Iscalimab/Placebo

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, Argentina

Novartis Investigative Site

Clayton, Victoria, Australia

Novartis Investigative Site

Guangzhou, Guangdong, China

Novartis Investigative Site

Nanjing, Jiangsu, China

Novartis Investigative Site

Shanghai, , China

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Novartis Investigative Site

Shinjuku Ku, Tokyo, Japan

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan

Novartis Investigative Site

Bydgoszcz, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Yekaterinburg, , Russia

Novartis Investigative Site

Gwangju, , South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Taichung, Taiwan ROC, Taiwan

Novartis Investigative Site

Taichung, , Taiwan

Novartis Investigative Site

Taichung, , Taiwan

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Bangkok, , Thailand

Countries

Argentina; Australia; China; Czechia; France; Germany; Hungary; Israel; Japan; Poland; Russia; South Korea; Spain; Taiwan; Thailand

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001508-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVAY736X2208

Identifier Type: -

Identifier Source: org_study_id