Systemic Lupus Erythematosus (SLE)
Conditions
Keywords
Systemic Lupus Erythematosus, SLE, Anti-CD40, anti-BAFF-receptor, B-cell depletion, BAFF-receptor blockade, ianalumab, VAY736, iscalimab, CFZ533
Brief summary
This study is designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of treatment with either VAY736 (ianalumab) or CFZ533 (iscalimab) in patients with systemic lupus erythematosus (SLE) to enable further development of these compounds as treatment in this disease population
Detailed description
The study consists of a 28-day screening period, a blinded treatment period of 28 weeks where randomized patients received treatment with investigational drug (ianalumab or iscalimab) or placebo. At the end of Week 29 visit, the patients enter the open label treatment phase where patients in active treatment group continued to receive active treatment and patients in placebo group started active treatment with ianalumab/iscalimab until Week 49. After completion of the open-label treatment period, all patients enter a Follow-Up period in order to monitor safety and efficacy up to Week 69. The Week 69 visit is the End of Study (EoS) visit for patients in Cohort 2 (CFZ533). Study duration for patients in Cohort 2 will be approximately 18 months. For Cohort 1 (VAY736). Patients who do not achieve B-cell recovery by Week 69 Visit will enter into a Secondary Follow-Up period until achieving B cell recovery criteria (B-cell count is at \>= 50 cells/µl or at least 80% of baseline levels). Safety follow-up visits will be scheduled as deemed appropriate until the patient achieves the B cell recovery criteria, followed by an EoS 4 weeks later.
Interventions
DRUGVAY736
150 mg powder in vial for solution for injection; after reconstitution to 150 mg/mL per vial, a dose of 300 mg
DRUGVAY736 Placebo
solution for injection; 0 mg/mL administered as 2 mL s.c. injection
DRUGCFZ533
150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion
DRUGCFZ533 Placebo
Placebo as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29 | Baseline, Week 17 to Week 29 | The primary endpoint is a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders. SRI-4 response is defined as below: * having \>= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND * no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND * \<10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline Sustained reduction in oral corticosteroid is defined as below: * =\< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND * no increase of that dose from Week 17 through Week 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29 | The patient's global assessment of disease activity was performed using a Visual Analogue Scale (VAS) of 100 mm ranging from no disease activity (score 0) to severe disease activity (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value. |
| Flare Rate and Time to First Flare | 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 |
| Time to First Flare | 18 months | Time to first flare, with flare defined as one new 'A' score or two or more 'B' score using BILAG -2004 |
| PK Cohort 1 - Cmax,ss | 18+ months | PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state) |
| Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29 | The Physician's global assessment (PhGA-VAS) of disease activity was performed using 100 mm VAS ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value. |
| PK Cohort 2 - Cmax,ss | 18 months | PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state). |
| PK Cohort 2 - Ctrough,ss | 18 months | PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state). |
| PD Cohort 2 (CFZ533): Total Soluble CD40 | 18 months | PD Cohort 2 (CFZ533): total soluble CD40 in plasma. |
| PK Cohort 1 - Ctrough,ss | 18+ months | PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state) |
Countries
Argentina, Australia, China, Czechia, France, Germany, Hungary, Israel, Japan, Poland, Russia, South Korea, Spain, Taiwan, Thailand
Participant flow
Recruitment details
This study is conducted in 31 centers in 15 countries: Argentina (1), Australia (1), China (3), Czech Republic (1), France (1), Germany (2), Hungary (2), Israel (1), Japan (5), Korea, Republic of (1), Poland (3), Russia (3), Spain (2), Taiwan (3), Thailand (2).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| 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. | 33 |
| 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. | 20 |
| 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. | 20 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Ongoing at the time of Interim Analysis Cut-off date | 19 | 13 | 5 | 4 |
| Overall Study | Physician Decision | 1 | 2 | 0 | 0 |
| Overall Study | Subject Decision | 3 | 5 | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort 1 VAY736 | Cohort 1 VAY736 Placebo | Cohort 2 CFZ533 | Cohort 2 CFZ533 Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42.0 Years STANDARD_DEVIATION 10.91 | 39.2 Years STANDARD_DEVIATION 10.46 | 37.4 Years STANDARD_DEVIATION 11.34 | 44.7 Years STANDARD_DEVIATION 12.47 | 40.8 Years STANDARD_DEVIATION 11.29 |
| Race/Ethnicity, Customized Asian | 9 Participants | 12 Participants | 7 Participants | 12 Participants | 40 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 21 Participants | 12 Participants | 8 Participants | 66 Participants |
| Sex: Female, Male Female | 32 Participants | 27 Participants | 20 Participants | 19 Participants | 98 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 0 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 33 | 0 / 20 | 0 / 20 | 0 / 107 | 0 / 31 | 0 / 31 | 0 / 20 | 0 / 16 | 0 / 98 |
| other Total, other adverse events | 21 / 34 | 21 / 33 | 9 / 20 | 12 / 20 | 63 / 107 | 16 / 31 | 22 / 31 | 8 / 20 | 14 / 16 | 60 / 98 |
| serious Total, serious adverse events | 1 / 34 | 4 / 33 | 0 / 20 | 1 / 20 | 6 / 107 | 5 / 31 | 3 / 31 | 0 / 20 | 3 / 16 | 11 / 98 |
Outcome results
Primary
Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29
The primary endpoint is a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders. SRI-4 response is defined as below: * having \>= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND * no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND * \<10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline Sustained reduction in oral corticosteroid is defined as below: * =\< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND * no increase of that dose from Week 17 through Week 29
Time frame: Baseline, Week 17 to Week 29
Population: Pharmacodynamic analysis set (PD analysis set)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 VAY736 | Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29 | 15 Participants |
| Cohort 1 VAY736 Placebo | Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29 | 3 Participants |
| Cohort 2 CFZ533 | Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29 | 8 Participants |
| Cohort 2 CFZ533 Placebo | Percentage of Participants With SLE Responder Index (SRI)-4 Response Status at Week 29 With Reduced Steroid Dose Maintained Between Weeks 17 and 29 | 6 Participants |
Secondary
Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity
The patient's global assessment of disease activity was performed using a Visual Analogue Scale (VAS) of 100 mm ranging from no disease activity (score 0) to severe disease activity (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.
Time frame: Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Population: Pharmacodynamic analysis set (PD analysis set). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 5 | -9.0 Unit on a scale | Standard Deviation 23.14 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 25 | -18.0 Unit on a scale | Standard Deviation 19.91 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 21 | -15.1 Unit on a scale | Standard Deviation 24.82 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 9 | -12.5 Unit on a scale | Standard Deviation 21.35 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 29 | -18.1 Unit on a scale | Standard Deviation 21.81 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 13 | -15.7 Unit on a scale | Standard Deviation 21.69 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 17 | -12.7 Unit on a scale | Standard Deviation 24.19 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 25 | -10.4 Unit on a scale | Standard Deviation 21.33 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 17 | -8.0 Unit on a scale | Standard Deviation 19.27 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 13 | -8.8 Unit on a scale | Standard Deviation 17.75 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 21 | -9.5 Unit on a scale | Standard Deviation 24.88 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 29 | -9.0 Unit on a scale | Standard Deviation 24.64 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 9 | -12.2 Unit on a scale | Standard Deviation 15.62 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 5 | -4.8 Unit on a scale | Standard Deviation 13.6 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 17 | -26.7 Unit on a scale | Standard Deviation 28.92 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 5 | -9.8 Unit on a scale | Standard Deviation 20.63 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 9 | -17.9 Unit on a scale | Standard Deviation 30.22 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 13 | -21.8 Unit on a scale | Standard Deviation 31.01 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 21 | -27.2 Unit on a scale | Standard Deviation 31.92 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 25 | -27.0 Unit on a scale | Standard Deviation 30.58 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 29 | -27.8 Unit on a scale | Standard Deviation 33.41 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 13 | -0.1 Unit on a scale | Standard Deviation 22.1 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 29 | -1.9 Unit on a scale | Standard Deviation 25.06 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 25 | 1.1 Unit on a scale | Standard Deviation 25.62 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 9 | 0.1 Unit on a scale | Standard Deviation 20.52 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 5 | -3.8 Unit on a scale | Standard Deviation 19.33 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 21 | -0.5 Unit on a scale | Standard Deviation 24.79 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Patient's Global Assessment (PGA) Visual Analog Scale (VAS) Assessing Patient's Global Disease Activity | Week 17 | 1.6 Unit on a scale | Standard Deviation 19.05 |
Secondary
Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity
The Physician's global assessment (PhGA-VAS) of disease activity was performed using 100 mm VAS ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question on how well the patient was doing with the disease considering all aspects affected by the disease. The investigator was then measuring the distance in mm from the left edge of the scale and entering the value.
Time frame: Baseline, Week 5, Week 9, Week 13, Week 17, Week 21, Week 25, Week 29
Population: Pharmacodynamic analysis set (PD analysis set). Only participants with a value at both Baseline and post-baseline visit included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 5 | -7.6 Unit on a scale | Standard Deviation 14.27 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 25 | -33.2 Unit on a scale | Standard Deviation 19.63 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 21 | -28.1 Unit on a scale | Standard Deviation 20.27 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 9 | -17.4 Unit on a scale | Standard Deviation 18.72 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 29 | -32.8 Unit on a scale | Standard Deviation 20.74 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 13 | -23.0 Unit on a scale | Standard Deviation 19.51 |
| Cohort 1 VAY736 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 17 | -26.2 Unit on a scale | Standard Deviation 19.14 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 25 | -18.6 Unit on a scale | Standard Deviation 17.62 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 17 | -14.2 Unit on a scale | Standard Deviation 16.38 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 13 | -13.6 Unit on a scale | Standard Deviation 16.72 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 21 | -17.9 Unit on a scale | Standard Deviation 16.24 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 29 | -19.4 Unit on a scale | Standard Deviation 16.04 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 9 | -10.9 Unit on a scale | Standard Deviation 13.54 |
| Cohort 1 VAY736 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 5 | -5.6 Unit on a scale | Standard Deviation 13.76 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 17 | -21.9 Unit on a scale | Standard Deviation 21.81 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 5 | -8.3 Unit on a scale | Standard Deviation 12.04 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 9 | -9.3 Unit on a scale | Standard Deviation 15.73 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 13 | -19.4 Unit on a scale | Standard Deviation 16.7 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 21 | -26.1 Unit on a scale | Standard Deviation 23.15 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 25 | -28.5 Unit on a scale | Standard Deviation 22.92 |
| Cohort 2 CFZ533 | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 29 | -28.7 Unit on a scale | Standard Deviation 22.89 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 13 | -20.3 Unit on a scale | Standard Deviation 19.26 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 29 | -24.5 Unit on a scale | Standard Deviation 19.25 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 25 | -24.6 Unit on a scale | Standard Deviation 19.12 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 9 | -13.7 Unit on a scale | Standard Deviation 18.43 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 5 | -12.5 Unit on a scale | Standard Deviation 15.94 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 21 | -24.1 Unit on a scale | Standard Deviation 17.71 |
| Cohort 2 CFZ533 Placebo | Changes Between Baseline and Week 29 in the Physicians' Global Assessment (PhGA) Visual Analog Scale (VAS) Assessing Patient's Overall Disease Activity | Week 17 | -22.2 Unit on a scale | Standard Deviation 20.1 |
Secondary
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
Time frame: 18 months
Secondary
PD Cohort 2 (CFZ533): Total Soluble CD40
PD Cohort 2 (CFZ533): total soluble CD40 in plasma.
Time frame: 18 months
Secondary
PK Cohort 1 - Cmax,ss
PK Cohort 1 (VAY736): free VAY736 serum concentration (Cmax at steady state)
Time frame: 18+ months
Secondary
PK Cohort 1 - Ctrough,ss
PK Cohort 1 (VAY736): free VAY736 serum concentration (Ctrough at steady state)
Time frame: 18+ months
Secondary
PK Cohort 2 - Cmax,ss
PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Cmax at steady state).
Time frame: 18 months
Secondary
PK Cohort 2 - Ctrough,ss
PK Cohort 2 (CFZ533): free CFZ533 concentration in plasma (Ctrough at steady state).
Time frame: 18 months
Secondary
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
Time frame: 18 months