Primary Sjögren's Syndrome
Conditions
Keywords
Sjögren's syndrome, CFZ533, ESSDAI
Brief summary
This study did evaluate the safety,tolerability and preliminary therapeutic efficacy of multiple doses of intravenous infusion of CFZ533 monoclonal antibody in patients with primary Sjögren's syndrome(pSS)
Interventions
DRUGCFZ533 placebo - Cohort 2
multiple doses of placebo intravenous infusion
DRUGCFZ533 active - Cohort 1
multiple doses of CFZ533 s.c. injection
DRUGCFZ533 placebo- Cohort 1
multiple doses of placebo s.c. injection
DRUGCFZ533 active - Cohort 2
multiple doses of CFZ533 intravenous infusion
DRUGCFZ533 active -Cohort 3
multiple doses of CFZ533 s.c. injection
DRUGCFZ533 active - Cohort 3
Single dose of CFZ533 i.v. infusion and multiple doses of CFZ533 s.c. injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary Sjögren's syndrome * ESSDAI score ≥ 6
Exclusion criteria
* Secondary Sjögren's syndrome * Receiving cyclosphosphamide, corticosteroid bolus with dose over 1 mg/kg, rituximab, belimunab, other immunosuppressives. * At significant risk for thromboembolic event * Clinically significant systemic infection * Significant elevated risk for infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline and Week 12 | The effect of CFZ533 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline and Week 12 | The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm). |
| Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline and Week 12 | The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm). |
| Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline and Week 12 | The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms. |
| Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Baseline and Week 12 | The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden. |
| Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Baseline and Week 12 | The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a possible range from 4-20. The reported total score has a range from 20-100. A reduction from baseline in MFI indicates improvement. |
| Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Baseline and Week 12 | The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden. |
Countries
Germany, Hungary, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A total of 69 patients were enrolled in Germany (1 center), Hungary (1 center), Switzerland (1 center), United Kingdom (3 centers), United States (3 centers)
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 CFZ533 CFZ533 3 mg/kg s.c. | 8 |
| Cohort 1 Placebo Placebo s.c./CFZ533 3 mg/kg s.c. | 4 |
| Cohort 2 CFZ533 CFZ533 10 mg/kg i.v. | 21 |
| Cohort 2 Placebo Placebo i.v./CFZ533 10 mg/kg i.v. | 11 |
| Cohort 3 CFZ533 Arm 1 CFZ533 600 mg s.c./CFZ533 300 mg s.c. | 13 |
| Cohort 3 CFZ533 Arm 2 CFZ533 10 mg/kg i.v./CFZ533 300 mg s.c. | 12 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 CFZ533 | Cohort 1 Placebo | Cohort 2 CFZ533 | Cohort 2 Placebo | Cohort 3 CFZ533 Arm 1 | Cohort 3 CFZ533 Arm 2 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.4 years | 48.8 years | 51.7 years | 50.6 years | 52.3 years | 54.8 years | 52.6 years |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants | 4 Participants | 18 Participants | 10 Participants | 12 Participants | 10 Participants | 61 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 19 Participants | 11 Participants | 12 Participants | 10 Participants | 64 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 5 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 | 0 / 21 | 0 / 11 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 8 / 8 | 4 / 4 | 11 / 21 | 7 / 11 | 12 / 13 | 12 / 12 |
| serious Total, serious adverse events | 1 / 8 | 0 / 4 | 1 / 21 | 0 / 11 | 0 / 13 | 1 / 12 |
Outcome results
Primary
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
The effect of CFZ533 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.
Time frame: Baseline and Week 12
Population: PD Population (all subjects with available Pharmacodynamics data and no protocol deviations with relevant impact on PD data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 9.6 units on a scale | Standard Deviation 5.45 |
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 12.0 units on a scale | Standard Deviation 3.78 |
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -2.4 units on a scale | Standard Deviation 2.77 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 9.8 units on a scale | Standard Deviation 3.3 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 11.8 units on a scale | Standard Deviation 3.86 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -2.0 units on a scale | Standard Deviation 2.45 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 4.2 units on a scale | Standard Deviation 4.25 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 10.6 units on a scale | Standard Deviation 4.44 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -6.4 units on a scale | Standard Deviation 4 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 9.7 units on a scale | Standard Deviation 9.05 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 11.0 units on a scale | Standard Deviation 5.16 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -1.3 units on a scale | Standard Deviation 8.06 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 7.2 units on a scale | Standard Deviation 6.69 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 12.7 units on a scale | Standard Deviation 6.06 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -5.5 units on a scale | Standard Deviation 5.49 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Baseline | 10.4 units on a scale | Standard Deviation 5.87 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Change from Baseline to Week 12 | -7.6 units on a scale | Standard Deviation 7.14 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) | Week 12 | 2.8 units on a scale | Standard Deviation 2.48 |
p-value: 0.39795% CI: [-3.7, 2.89]Repeated measures model
p-value: 0.00995% CI: [-9.46, -0.96]Repeated measures model
p-value: 0.34495% CI: [-2.78, 7.45]Repeated measures model
Secondary
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI)
The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms.
Time frame: Baseline and Week 12
Population: PD Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 5.71 units on a scale | Standard Deviation 1.24 |
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 6.75 units on a scale | Standard Deviation 1.909 |
| Cohort 1 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | -1.04 units on a scale | Standard Deviation 1.201 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 7.08 units on a scale | Standard Deviation 2.251 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 7.00 units on a scale | Standard Deviation 1.826 |
| Cohort 1 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | 0.08 units on a scale | Standard Deviation 0.631 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 5.03 units on a scale | Standard Deviation 2.413 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 6.71 units on a scale | Standard Deviation 1.678 |
| Cohort 2 CFZ533 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | -1.68 units on a scale | Standard Deviation 1.954 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 6.24 units on a scale | Standard Deviation 2.039 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 7.18 units on a scale | Standard Deviation 1.486 |
| Cohort 2 Placebo | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | -0.94 units on a scale | Standard Deviation 1.246 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 5.33 units on a scale | Standard Deviation 2.269 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 7.00 units on a scale | Standard Deviation 1.604 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | -1.67 units on a scale | Standard Deviation 1.841 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Baseline | 6.00 units on a scale | Standard Deviation 2.344 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Change from Baseline to Week 12 | -1.17 units on a scale | Standard Deviation 2.333 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) | Week 12 | 4.83 units on a scale | Standard Deviation 2.552 |
p-value: 0.20595% CI: [-2.97, 0.8]Repeated measures model
p-value: 0.18895% CI: [-2.41, 0.5]Repeated measures model
p-value: 0.66395% CI: [-2.08, 1.35]Repeated measures model
Secondary
Change From Baseline in Multidimensional Fatigue Inventory (MFI)
The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a possible range from 4-20. The reported total score has a range from 20-100. A reduction from baseline in MFI indicates improvement.
Time frame: Baseline and Week 12
Population: PD Population for Cohort 1 and Cohort 2. Data were not collected from participants in Cohort 3 CFZ533 Arm 1 and Cohort 3 CFZ533 Arm 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Change from Baseline to Week 12 | -0.6 units on a scale | Standard Deviation 8.12 |
| Cohort 1 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Baseline | 54.1 units on a scale | Standard Deviation 16.23 |
| Cohort 1 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Week 12 | 53.5 units on a scale | Standard Deviation 13.96 |
| Cohort 1 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Change from Baseline to Week 12 | -8.3 units on a scale | Standard Deviation 8.18 |
| Cohort 1 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Week 12 | 69.8 units on a scale | Standard Deviation 17.75 |
| Cohort 1 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Baseline | 78.0 units on a scale | Standard Deviation 17.8 |
| Cohort 2 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Change from Baseline to Week 12 | -14.5 units on a scale | Standard Deviation 18.09 |
| Cohort 2 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Week 12 | 55.2 units on a scale | Standard Deviation 16.65 |
| Cohort 2 CFZ533 | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Baseline | 70.0 units on a scale | Standard Deviation 17.51 |
| Cohort 2 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Change from Baseline to Week 12 | -2.9 units on a scale | Standard Deviation 12.37 |
| Cohort 2 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Week 12 | 63.3 units on a scale | Standard Deviation 16.99 |
| Cohort 2 Placebo | Change From Baseline in Multidimensional Fatigue Inventory (MFI) | Baseline | 66.2 units on a scale | Standard Deviation 17.59 |
p-value: 0.80795% CI: [-10.48, 13.15]Repeated measures model
p-value: 0.07495% CI: [-20.66, 1.01]Repeated measures model
Secondary
Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS)
The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).
Time frame: Baseline and Week 12
Population: PD Population (Statistical Analysis only for Cohort 1 and 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 49.06 units on a scale | Standard Deviation 24.519 |
| Cohort 1 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | 1.94 units on a scale | Standard Deviation 26.023 |
| Cohort 1 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 47.13 units on a scale | Standard Deviation 32.406 |
| Cohort 1 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 75.50 units on a scale | Standard Deviation 24.393 |
| Cohort 1 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | 2.50 units on a scale | Standard Deviation 17.861 |
| Cohort 1 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 73.00 units on a scale | Standard Deviation 12.623 |
| Cohort 2 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | -23.05 units on a scale | Standard Deviation 26.92 |
| Cohort 2 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 58.43 units on a scale | Standard Deviation 19.881 |
| Cohort 2 CFZ533 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 34.85 units on a scale | Standard Deviation 24.564 |
| Cohort 2 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 54.91 units on a scale | Standard Deviation 21.002 |
| Cohort 2 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 42.27 units on a scale | Standard Deviation 24.483 |
| Cohort 2 Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | -12.64 units on a scale | Standard Deviation 26.871 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | -25.23 units on a scale | Standard Deviation 29.833 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 63.69 units on a scale | Standard Deviation 25.799 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 38.46 units on a scale | Standard Deviation 26.965 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Week 12 | 53.17 units on a scale | Standard Deviation 25.305 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Baseline | 52.08 units on a scale | Standard Deviation 22.138 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) | Change from Baseline to Week 12 | 1.08 units on a scale | Standard Deviation 23.283 |
p-value: 0.45695% CI: [-36.2, 17.3]Repeated measures model
p-value: 0.37695% CI: [-26.67, 10.39]Repeated measures model
Secondary
Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS)
The visual analogue scale used is a 100 mm VAS ranging from no disease (0 mm) to maximal disease activity (100 mm).
Time frame: Baseline and Week 12
Population: PD Population (Statistical Analysis only for Cohort 1 and 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 40.5 units on a scale | Standard Deviation 16.42 |
| Cohort 1 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -17.6 units on a scale | Standard Deviation 24.6 |
| Cohort 1 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 57.9 units on a scale | Standard Deviation 15.72 |
| Cohort 1 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 57.8 units on a scale | Standard Deviation 17.19 |
| Cohort 1 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 55.5 units on a scale | Standard Deviation 12.01 |
| Cohort 1 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -2.3 units on a scale | Standard Deviation 10.9 |
| Cohort 2 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -28.7 units on a scale | Standard Deviation 16.02 |
| Cohort 2 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 22.8 units on a scale | Standard Deviation 11.78 |
| Cohort 2 CFZ533 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 51.9 units on a scale | Standard Deviation 12.62 |
| Cohort 2 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 34.2 units on a scale | Standard Deviation 13.9 |
| Cohort 2 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -13.7 units on a scale | Standard Deviation 22.97 |
| Cohort 2 Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 47.9 units on a scale | Standard Deviation 19.18 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -25.0 units on a scale | Standard Deviation 15.3 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 25.4 units on a scale | Standard Deviation 16.65 |
| Cohort 3 CFZ533 Arm 1 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 50.4 units on a scale | Standard Deviation 12.39 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Baseline | 47.1 units on a scale | Standard Deviation 18.34 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Week 12 | 27.3 units on a scale | Standard Deviation 16.74 |
| Cohort 3 CFZ533 Arm 2 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) | Change from Baseline to Week 12 | -19.8 units on a scale | Standard Deviation 21.96 |
p-value: 0.16195% CI: [-37.9, 7.38]Repeated measures model
p-value: 0.01795% CI: [-21.94, -2.38]Repeated measures model
Secondary
Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score
The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.
Time frame: Baseline and Week 12
Population: PD Population for Cohort 1 and Cohort 2. Data were not collected from participants in Cohort 3 CFZ533 Arm 1 and Cohort 3 CFZ533 Arm 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Baseline | 46.838 units on a scale | Standard Deviation 7.8986 |
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Change from Baseline to Week 12 | 0.373 units on a scale | Standard Deviation 6.3174 |
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Week 12 | 48.076 units on a scale | Standard Deviation 12.5197 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Baseline | 43.118 units on a scale | Standard Deviation 16.3701 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Change from Baseline to Week 12 | 0.543 units on a scale | Standard Deviation 4.0309 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Week 12 | 43.660 units on a scale | Standard Deviation 13.9997 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Week 12 | 44.688 units on a scale | Standard Deviation 10.2469 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Baseline | 37.071 units on a scale | Standard Deviation 12.2914 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Change from Baseline to Week 12 | 8.212 units on a scale | Standard Deviation 11.1378 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Baseline | 39.512 units on a scale | Standard Deviation 15.4212 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Change from Baseline to Week 12 | 4.273 units on a scale | Standard Deviation 10.7671 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score | Week 12 | 43.785 units on a scale | Standard Deviation 13.2982 |
p-value: 0.98695% CI: [-8.49, 8.35]Repeated measures model
p-value: 0.17595% CI: [-1.81, 9.48]Repeated measures model
Secondary
Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score
The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.
Time frame: Baseline and Week 12
Population: PD Population for Cohort 1 and Cohort 2. Data were not collected from participants in Cohort 3 CFZ533 Arm 1 and Cohort 3 CFZ533 Arm 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Baseline | 42.218 units on a scale | Standard Deviation 6.9437 |
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Change from Baseline to Week 12 | -1.005 units on a scale | Standard Deviation 4.538 |
| Cohort 1 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Week 12 | 40.374 units on a scale | Standard Deviation 9.223 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Baseline | 31.215 units on a scale | Standard Deviation 12.5562 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Change from Baseline to Week 12 | 4.908 units on a scale | Standard Deviation 4.2349 |
| Cohort 1 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Week 12 | 36.123 units on a scale | Standard Deviation 13.0002 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Week 12 | 44.001 units on a scale | Standard Deviation 9.3943 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Baseline | 38.163 units on a scale | Standard Deviation 8.5905 |
| Cohort 2 CFZ533 | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Change from Baseline to Week 12 | 5.546 units on a scale | Standard Deviation 7.176 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Baseline | 38.819 units on a scale | Standard Deviation 5.9689 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Change from Baseline to Week 12 | 1.479 units on a scale | Standard Deviation 8.2497 |
| Cohort 2 Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score | Week 12 | 40.298 units on a scale | Standard Deviation 8.9392 |
p-value: 0.17295% CI: [-13.91, 2.91]Repeated measures model
p-value: 0.17595% CI: [-1.81, 9.48]Repeated measures model