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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03656562
Recruitment Status : Recruiting
First Posted : September 4, 2018
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus (SLE) Drug: VAY736 Drug: VAY736 Placebo Drug: CFZ533 Drug: CFZ533 Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The investigational drug or placebo will be administered on top of SLE background therapy. Patients will be randomized at baseline into one of two treatment cohorts (VAY736 or CFZ533) and to either active or placebo double blind treatment within that cohort. From Week 29 onwards all patients will receive open label active treatment until week 53 in the respective cohort.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: 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
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : December 19, 2018
Estimated Primary Completion Date : August 13, 2021
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

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




Primary Outcome Measures :
  1. SRI-4 response status [ Time Frame: 29 Weeks ]

    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.



Secondary Outcome Measures :
  1. PhGA VAS - overall disease activity [ Time Frame: from Baseline to Week 29 ]
    Changes between baseline and Week 29 in the Physicians' Global Assessment (PhGA) visual analog scale (VAS) assessing patient's overall disease activity

  2. PGA VAS - global disease activity [ Time Frame: from baseline to 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

  3. Flare rate and time to first flare [ Time Frame: 18 months ]
    Flare rate and time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004

  4. Time to first flare [ Time Frame: 18 months ]
    Time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004

  5. PK Cohort 1 - Cmax,ss [ Time Frame: 18+ months ]
    PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)

  6. PK Cohort 1 - Ctrough,ss [ Time Frame: 18+ months ]
    PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)

  7. PK Cohort 2 - Cmax,ss [ Time Frame: 18 months ]
    PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).

  8. PK Cohort 2 - Ctrough,ss [ Time Frame: 18 months ]
    PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or nephrotic range proteinuria (above 2 g/day), corresponding to a urine protein creatinine ratio of approx. 200 mg/mmol or 1.77 g/g, currently 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03656562


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +81337978748

Locations
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Argentina
Novartis Investigative Site Recruiting
Ciudad Autonoma de Bs As, Argentina, C1015ABO
Australia, Victoria
Novartis Investigative Site Recruiting
Clayton, Victoria, Australia, 3168
China, Jiangsu
Novartis Investigative Site Recruiting
Nanjing, Jiangsu, China, 210008
Czechia
Novartis Investigative Site Recruiting
Praha 2, Czechia, 128 50
France
Novartis Investigative Site Recruiting
Lille, France, 59000
Novartis Investigative Site Recruiting
Marseille, France, 13003
Novartis Investigative Site Recruiting
Paris Cedex 13, France, 75651
Novartis Investigative Site Recruiting
Pessac Cedex, France, 33604
Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 10117
Novartis Investigative Site Recruiting
Freiburg, Germany, 79106
Hungary
Novartis Investigative Site Recruiting
Budapest, Hungary, 1023
Novartis Investigative Site Recruiting
Debrecen, Hungary, 4032
Israel
Novartis Investigative Site Recruiting
Jerusalem, Israel
Novartis Investigative Site Recruiting
Ramat Gan, Israel, 5265601
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 457 8510
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 460-0001
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104-8560
Novartis Investigative Site Recruiting
Shinjuku ku, Tokyo, Japan, 162 8655
Novartis Investigative Site Recruiting
Shinjuku-ku, Tokyo, Japan, 160 8582
Korea, Republic of
Novartis Investigative Site Recruiting
Suwon si, Gyeonggi Do, Korea, Republic of, 16499
Novartis Investigative Site Recruiting
Gwangju, Korea, Republic of, 61469
Poland
Novartis Investigative Site Recruiting
Bydgoszcz, Poland, 85 168
Novartis Investigative Site Recruiting
Poznan, Poland, 60-218
Novartis Investigative Site Recruiting
Warszawa, Poland, 00-874
Russian Federation
Novartis Investigative Site Recruiting
Ekaterinburg, Russian Federation, 620028
Novartis Investigative Site Recruiting
Saint-Petersburg, Russian Federation, 194044
Novartis Investigative Site Recruiting
St Petersburg, Russian Federation, 190068
Spain
Novartis Investigative Site Recruiting
Barcelona, Barcelona/ Cataluny/Espanya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Barcelona, Spain, 08041
Taiwan
Novartis Investigative Site Recruiting
Taichung, Taiwan, 40447
Novartis Investigative Site Recruiting
Taichung, Taiwan, 40705
Thailand
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10400
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10700
Novartis Investigative Site Recruiting
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03656562    
Other Study ID Numbers: CVAY736X2208
First Posted: September 4, 2018    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Systemic Lupus Erythematosus (SLE)
Anti-CD40
anti-BAFF-receptor
B-cell depletion
BAFF-receptor blockade
ianalumab
VAY736
iscalimab
CFZ533
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs