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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03656562
Ethics application status
Date submitted
19/07/2018
Date registered
4/09/2018

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
2018-001508-12
Secondary ID [2] 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 - 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.

Placebo comparator: 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.

Experimental: 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.

Placebo comparator: 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.


Treatment: Drugs: VAY736
150 mg powder in vial for solution for injection; after reconstitution to 150 mg/mL per vial, a dose of 300 mg

Treatment: Drugs: VAY736 Placebo
solution for injection; 0 mg/mL administered as 2 mL s.c. injection

Treatment: Drugs: CFZ533
150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion

Treatment: Drugs: CFZ533 Placebo
Placebo as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29
Timepoint [1] 0 0
Baseline, Week 17 to Week 29
Secondary outcome [1] 0 0
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
Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Secondary outcome [2] 0 0
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
Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Secondary outcome [3] 0 0
Flare Rate and Time to First Flare
Timepoint [3] 0 0
18 months
Secondary outcome [4] 0 0
Time to First Flare
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
PK Cohort 1 - Cmax,ss
Timepoint [5] 0 0
18+ months
Secondary outcome [6] 0 0
PK Cohort 1 - Ctrough,ss
Timepoint [6] 0 0
18+ months
Secondary outcome [7] 0 0
PK Cohort 2 - Cmax,ss
Timepoint [7] 0 0
18 months
Secondary outcome [8] 0 0
PK Cohort 2 - Ctrough,ss
Timepoint [8] 0 0
18 months
Secondary outcome [9] 0 0
PD Cohort 2 (CFZ533): Total Soluble CD40
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 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
Minimum age
18 Years
Maximum age
75 Years
Sex
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 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.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/04/2026
Actual
Sample size
Target
Accrual to date
Final
107
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
Buenos Aires
Country [2] 0 0
China
State/province [2] 0 0
Guangdong
Country [3] 0 0
China
State/province [3] 0 0
Jiangsu
Country [4] 0 0
China
State/province [4] 0 0
Shanghai
Country [5] 0 0
Czechia
State/province [5] 0 0
Praha 2
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
Ramat Gan
Country [12] 0 0
Japan
State/province [12] 0 0
Aichi
Country [13] 0 0
Japan
State/province [13] 0 0
Tokyo
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Gwangju
Country [15] 0 0
Poland
State/province [15] 0 0
Bydgoszcz
Country [16] 0 0
Poland
State/province [16] 0 0
Poznan
Country [17] 0 0
Poland
State/province [17] 0 0
Warszawa
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Ekaterinburg
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Moscow
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Saint Petersburg
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taiwan ROC
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taichung
Country [25] 0 0
Thailand
State/province [25] 0 0
Bangkok

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03656562