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

NCT03656562 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CVAY736X22082018-001508-12
• Study Type: interventional
• Target: 107
• Locations: 15 countries
• Sites: 31

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

Conditions

Systemic Lupus Erythematosus (SLE)

Keywords

Systemic Lupus Erythematosus; SLE; Anti-CD40; anti-BAFF-receptor; B-cell depletion; BAFF-receptor blockade; ianalumab; VAY736; iscalimab; CFZ533

Outcome Measures

Primary Outcomes (1)

• 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 is 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 Outcomes (9)

• Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity

  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

  Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29

• Flare Rate and Time to First Flare

  18 months

• Time to First Flare

  18 months

• PK Cohort 1 - Cmax,ss

  18+ months

Study Arms (4)

Cohort 1 VAY736

EXPERIMENTAL

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

Cohort 1 VAY736 Placebo

PLACEBO COMPARATOR

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; Drug: VAY736 Placebo

Cohort 2 CFZ533

EXPERIMENTAL

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

Cohort 2 CFZ533 Placebo

PLACEBO COMPARATOR

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; Drug: CFZ533 Placebo

Interventions

VAY736 DRUG

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

Also known as: Ianalumab

Cohort 1 VAY736; Cohort 1 VAY736 Placebo

VAY736 Placebo DRUG

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

Also known as: Ianalumab/Placebo

Cohort 1 VAY736 Placebo

CFZ533 DRUG

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

Also known as: Iscalimab

Cohort 2 CFZ533; Cohort 2 CFZ533 Placebo

CFZ533 Placebo DRUG

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

Also known as: Iscalimab/Placebo

Cohort 2 CFZ533 Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

Location

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210008, China

Location

Novartis Investigative Site

Shanghai, 200127, China

Location

Novartis Investigative Site

Prague, 128 00, Czechia

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Budapest, 1023, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 457 8510, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 460-0001, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 8560, Japan

Location

Novartis Investigative Site

Shinjuku Ku, Tokyo, 162 8655, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160 8582, Japan

Location

Novartis Investigative Site

Bydgoszcz, 85 168, Poland

Location

Novartis Investigative Site

Poznan, 60-218, Poland

Location

Novartis Investigative Site

Warsaw, 00-874, Poland

Location

Novartis Investigative Site

Moscow, 115522, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620144, Russia

Location

Novartis Investigative Site

Gwangju, 61469, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Taichung, Taiwan ROC, 40201, Taiwan

Location

Novartis Investigative Site

Taichung, 40447, Taiwan

Location

Novartis Investigative Site

Taichung, 407219, Taiwan

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

ianalumab; iscalimab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, investigator staff, persons performing the assessments, and the clinical trial team (CTT) will remain blind to the identity of the treatment within each cohort from the time of randomization until end of the Week 29 visit
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: September 4, 2018
• Study Start: December 19, 2018
• Primary Completion: July 27, 2022
• Study Completion: April 28, 2025
• Last Updated: October 7, 2025
• Results First Posted: June 6, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

JP (5); PL (3); CZ (1); DE (2); IL (1); RU (3); ES (2); TW (3); AU (1); FR (1); TH (2); KR (1); CN (3); HU (2); AR (1)