Main
|
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
|
EUCTR |
Last refreshed on:
|
16 December 2024 |
Main ID: |
EUCTR2018-001508-12-FR |
Date of registration:
|
13/11/2018 |
Prospective Registration:
|
Yes |
Primary sponsor: |
|
Public title:
|
Study the efficacy and safety of VAY736 and CFZ533 in patients with systemic lupus erythematosus (SLE)
|
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) |
Date of first enrolment:
|
05/02/2019 |
Target sample size:
|
120 |
Recruitment status: |
Not Recruiting |
URL:
|
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001508-12 |
Study type:
|
Interventional clinical trial of medicinal product |
Study design:
|
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
|
Phase:
|
Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
|
|
Countries of recruitment
|
Argentina
|
Australia
|
China
|
Czech Republic
|
France
|
Germany
|
Hungary
|
Israel
|
Japan
|
Korea, Republic of
|
Poland
|
Russian Federation
|
Spain
|
Taiwan
|
Thailand
| |
Contacts
|
Name:
|
Information&Communication Médicales
|
Address:
|
2 et 4 rue Lionel Terray
92500
Rueil-Malmaison
France |
Telephone:
|
+33155476600 |
Email:
|
icm.phfr@novartis.com |
Affiliation:
|
Novartis Pharma S.A.S. |
|
Name:
|
Information&Communication Médicales
|
Address:
|
2 et 4 rue Lionel Terray
92500
Rueil-Malmaison
France |
Telephone:
|
+33155476600 |
Email:
|
icm.phfr@novartis.com |
Affiliation:
|
Novartis Pharma S.A.S. |
| |
Key inclusion & exclusion criteria
|
Inclusion criteria: - Written informed consent must be obtained before any assessment is performed
- Male and female patients 18 to 75 years of age
- 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 antimalarials 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
- Other protocol-defined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
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
- Other protocol-defined exclusion criteria may apply
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
|
Health Condition(s) or Problem(s) studied
|
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
|
Systemic lupus erythematosus (SLE) MedDRA version: 20.0
Level: PT
Classification code 10042945
Term: Systemic lupus erythematosus
System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
|
Intervention(s)
|
Product Code: VAY736 Pharmaceutical Form: Powder for solution for injection/infusion INN or Proposed INN: ianalumab Current Sponsor code: VAY736 Other descriptive name: VAY736 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150- Pharmaceutical form of the placebo: Concentrate for solution for injection/infusion Route of administration of the placebo: Subcutaneous use
Product Code: CFZ533 Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: iscalimab Current Sponsor code: CFZ533 Other descriptive name: CFZ533 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 150- Pharmaceutical form of the placebo: Concentrate for solution for injection/infusion Route of administration of the placebo: Intravenous use
|
Primary Outcome(s)
|
Timepoint(s) of evaluation of this end point: 29 Weeks
|
Main Objective: The primary objective of this study is to determine the effect of VAY736 and of CFZ533 versus their respective placebo on disease activity in SLE patients using the SRI-4 index.
|
Primary end point(s): SRI-4 response status at Week 29 with reduced steroid dose maintained between Weeks 17 and 29
|
Secondary Objective: - To assess safety and tolerability in patients with SLE by recording all adverse events - To determine the change from baseline in the Physicians’ Global Assessment (PhGA) at Week 29 by using a visual analogue scale (VAS) - To determine the change from baseline in the Patient's Global Assessment (PGA) at Week 29 by using a patients VAS - To determine the pharmacokinetics (PK) of multiple doses of VAY736 (s.c.) and CFZ533 (i.v.) in SLE patients by analyzing PK concentrations in blood - To assess the effect of VAY736 and of CFZ533 versus their respective placebo to prevent disease flares in SLE patient’s using BILAG-2004 - To evaluate the immunogenicity of multiple doses of VAY736 (s.c.) or CFZ533 (i.v.) in SLE patients by analyzing anti-drug antibodies in blood - To evaluate the pharmacodynamics (PD; rate, extent and duration of target engagement) of multiple doses of CFZ533 in SLE patients by analyzing total soluble CD40 in plasma
|
Secondary Outcome(s)
|
Secondary end point(s): - Changes between baseline and Week 29 in the PhGA visual analog scale (VAS) assessing patient’s overall disease activity
- Changes between baseline and Week 29 in the PGA visual analog scale (VAS) assessing patient’s global disease activity
- Flare rate and time to first flare, with flare defined as one new ‘A’ score or two or more ‘B’ score using BILAG-2004
- Time to first flare, with flare defined as one new ‘A’ score or two or more ‘B’ score using BILAG -2004
- PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)
- PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)
- PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).
- PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).
- PD Cohort 2 (CFZ533): total soluble CD40 in plasma.
|
Timepoint(s) of evaluation of this end point: 29 Weeks
29 Weeks
18 months
18 months
End of Study
End of Study
18 months
18 months
18 months
|
Secondary ID(s)
|
2018-001508-12-CZ
|
CVAY736X2208
|
Source(s) of Monetary Support
|
Novartis Pharma AG
|
Ethics review
|
Status: Approved
Approval date: 05/02/2019
Contact:
|
Results
|
Results available:
|
|
Date Posted:
|
|
Date Completed:
|
|
URL:
|
|
|
|