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

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ClinicalTrials.gov Identifier: NCT03656562
Recruitment Status : Recruiting
First Posted : September 3, 2018
Last Update Posted : May 30, 2019
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 : April 15, 2021
Estimated Study Completion Date : August 2, 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 either anti-double stranded DNA (anti-ds DNA), anti-Ro (SSA), anti-La (SSB), anti-nuclear ribonucleoprotein (anti-RNP) or anti-Smith (anti-Sm)
  • Currently receiving corticosteroids and/or anti-malarials and/or another DMARD on a stable dose according to protocol requirements
  • SLEDAI-2K score of ≥6 at screening
  • BILAG 2004 score of ≥1A or ≥2B in mucocutaneous 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 partial thromboplastin time (PTT) 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 mycophenolate mofetil
  • Within 24 weeks: cyclophosphamide, intravenous Ig, plasmapheresis, anti-TNF-a mAb, CTLA4-Fc Ig (abatacept) or BAFF targeting agents (e.g., belimumab)
  • Any B-cell depleting therapies (administered >1 year ago) and with a Bcell count <50 cells/μL at time of screening; or, any B-cell depleting therapies within 52 weeks prior to screening
  • Evidence of active 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
  • History of WHO Class III-IV renal involvement with proliferative disease or nephrotic range proteinuria (above 2 g/day) 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 2month 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

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

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Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03656562     History of Changes
Other Study ID Numbers: CVAY736X2208
First Posted: September 3, 2018    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
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

Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases