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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03656562




Registration number
NCT03656562
Ethics application status
Date submitted
19/07/2018
Date registered
3/09/2018
Date last updated
19/07/2019

Titles & IDs
Public title
Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients
Scientific 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)
Secondary ID [1] 0 0
CVAY736X2208
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus (SLE) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - VAY736
Treatment: Drugs - VAY736 Placebo
Treatment: Drugs - CFZ533
Treatment: Drugs - CFZ533 Placebo

Experimental: Cohort 1 VAY736 - multiple doses of VAY736, s.c.

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.

Experimental: Cohort 2 CFZ533 - multiple doses of CFZ533, i.v.

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.


Treatment: Drugs: VAY736
Powder for solution for injection

Treatment: Drugs: VAY736 Placebo
Solution for injection

Treatment: Drugs: CFZ533
Concentrate for solution for infusion

Treatment: Drugs: CFZ533 Placebo
Solution for infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
SRI-4 response status - 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.
Timepoint [1] 0 0
29 Weeks
Secondary outcome [1] 0 0
PhGA VAS - overall disease activity - Changes between baseline and Week 29 in the Physicians' Global Assessment (PhGA) visual analog scale (VAS) assessing patient's overall disease activity
Timepoint [1] 0 0
from Baseline to Week 29
Secondary outcome [2] 0 0
PGA VAS - global disease activity - Changes between baseline and Week 29 in the Patient's Global Assessment (PGA) visual analog scale (VAS) assessing patient's global disease activity
Timepoint [2] 0 0
from baseline to Week 29
Secondary outcome [3] 0 0
Flare rate and time to first flare - Flare rate and time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004
Timepoint [3] 0 0
18 months
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
PK Cohort 1 - Cmax,ss - PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)
Timepoint [5] 0 0
18+ months
Secondary outcome [6] 0 0
PK Cohort 1 - Ctrough,ss - PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)
Timepoint [6] 0 0
18+ months
Secondary outcome [7] 0 0
PK Cohort 2 - Cmax,ss - PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).
Timepoint [7] 0 0
18 months
Secondary outcome [8] 0 0
PK Cohort 2 - Ctrough,ss - PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).
Timepoint [8] 0 0
18 months
Secondary outcome [9] 0 0
PD Cohort 2 (CFZ533): total soluble CD40 - PD Cohort 2 (CFZ533): total soluble CD40 in plasma.
Timepoint [9] 0 0
18 months

Eligibility
Key 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 in the mucocutaneous domain or one "B" score in the
mucocutaneous domain plus an "A" or "B" score in another domain at screening

- Weigh at least 40 kg at screening
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Ciudad Autonoma de Bs As
Country [2] 0 0
Czechia
State/province [2] 0 0
Praha 2
Country [3] 0 0
France
State/province [3] 0 0
Lille
Country [4] 0 0
France
State/province [4] 0 0
Marseille
Country [5] 0 0
France
State/province [5] 0 0
Paris Cedex 13
Country [6] 0 0
France
State/province [6] 0 0
Pessac Cedex
Country [7] 0 0
Germany
State/province [7] 0 0
Berlin
Country [8] 0 0
Germany
State/province [8] 0 0
Freiburg
Country [9] 0 0
Hungary
State/province [9] 0 0
Budapest
Country [10] 0 0
Hungary
State/province [10] 0 0
Debrecen
Country [11] 0 0
Israel
State/province [11] 0 0
Jerusalem
Country [12] 0 0
Israel
State/province [12] 0 0
Ramat Gan
Country [13] 0 0
Japan
State/province [13] 0 0
Aichi
Country [14] 0 0
Japan
State/province [14] 0 0
Tokyo
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Gyeonggi Do
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Gwangju
Country [17] 0 0
Poland
State/province [17] 0 0
Bydgoszcz
Country [18] 0 0
Poland
State/province [18] 0 0
Poznan
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Ekaterinburg
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Saint-Petersburg
Country [22] 0 0
Russian Federation
State/province [22] 0 0
St Petersburg
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona/ Cataluny/Espanya
Country [24] 0 0
Spain
State/province [24] 0 0
Catalunya
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taichung
Country [27] 0 0
Thailand
State/province [27] 0 0
Bangkok
Country [28] 0 0
Thailand
State/province [28] 0 0
Chiang Mai

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT03656562
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
+41613241111
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03656562