Primary Sjögren's Syndrome
Conditions
Brief summary
This Study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary therapeutic efficacy of oral administrations of CDZ173 in patients with primary Sjögren's syndrome.
Detailed description
This study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary therapeutic efficacy of oral administrations of CDZ173, a selective PI3K delta inhibitor, for 12 weeks, in patients with primary Sjögren's syndrome. Data from this study will provide the basis for further development of the compound for the treatment of primary Sjögren's syndrome.
Interventions
DRUGCDZ173
DRUGPlacebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary Sjögren's syndrome (pSS) * ESSDAI score ≥ 6 at screening visit
Exclusion criteria
* Secondary Sjögren's syndrome Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | up to Day 85 | Safety and tolerability of CDZ173 in patients with primary Sjögren's syndrome up to End of Treatment Day 85 |
| Change From Baseline in the EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) After 12 Weeks of Treatment Day 85 | Baseline and 12 weeks (Day 85) | The ESSPRI is an established disease outcome measure for Sjögren's syndrome. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baseline in Multidimensional Fatigue Inventory (MFI) After 12 Weeks of Treatment (Day 85) | Baseline and 12 weeks (Day 85) | The Multidimensional Fatigue Inventory (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. The reported total score has a range from 20-100, higher scores are associated with greater fatigue. |
| Change From Baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) After 12 Weeks of Treatment Day 85 | Baseline and 12 weeks (Day 85) | The ESSDAI is an established disease outcome measure for Sjögren's syndrome. 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. A reduction from baseline (i.e., a negative change from baseline) in the ESSDAI score is indicative of improvement in a patient.). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). |
| Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) After 12 Weeks of Treatment Day 85 | Baseline and 12 weeks | A reduction from baseline (or, a negative change from baseline) in patient global VAS assessment score indicates improvement in patients. 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 Physician Global Assessment of the Patient's Overall Disease Activity (Physician VAS) After 12 Weeks of Treatment Day 85 | Baseline and 12 weeks (Day 85) | A reduction from baseline (i.e., a negative change from baseline) in physician global VAS assessment score indicates improvement in patients. 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 the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85 | Baseline and 12 weeks (Day 85) | 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
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CDZ173 Capsule BID | 20 |
| Placebo Capsule matching Placebo BID | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Subject/Guardian Decision | 2 | 0 |
Baseline characteristics
| Characteristic | CDZ173 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 13.85 | 44.7 years STANDARD_DEVIATION 11.58 | 47.3 years STANDARD_DEVIATION 13.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 10 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 17 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 19 / 20 | 8 / 10 |
| serious Total, serious adverse events | 1 / 20 | 0 / 10 |
Outcome results
Primary
Change From Baseline in the EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) After 12 Weeks of Treatment Day 85
The ESSPRI is an established disease outcome measure for Sjögren's syndrome. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10.
Time frame: Baseline and 12 weeks (Day 85)
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CDZ173 | Change From Baseline in the EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) After 12 Weeks of Treatment Day 85 | -1.778 total score on scale | Standard Deviation 2.4509 |
| Placebo | Change From Baseline in the EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) After 12 Weeks of Treatment Day 85 | -0.741 total score on scale | Standard Deviation 1.3517 |
95% CI: [-3.343, 1.937]
Primary
Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85
Safety and tolerability of CDZ173 in patients with primary Sjögren's syndrome up to End of Treatment Day 85
Time frame: up to Day 85
Population: Safety Analysis Set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CDZ173 | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Death | 0 count of participants |
| CDZ173 | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Participants with at least one AE | 20 count of participants |
| CDZ173 | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Participants with at least one SAE | 1 count of participants |
| Placebo | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Participants with at least one AE | 8 count of participants |
| Placebo | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Participants with at least one SAE | 0 count of participants |
| Placebo | Number of Participants With Primary Sjögren's Syndrome With Adverse Events and Death up to Day 85 | Death | 0 count of participants |
Secondary
Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) After 12 Weeks of Treatment Day 85
A reduction from baseline (or, a negative change from baseline) in patient global VAS assessment score indicates improvement in patients. 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 12 weeks
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CDZ173 | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) After 12 Weeks of Treatment Day 85 | -4.83 total score on a scale | Standard Error 7.268 |
| Placebo | Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) After 12 Weeks of Treatment Day 85 | 2.87 total score on a scale | Standard Error 8.412 |
95% CI: [-29.75, 14.37]
Secondary
Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (Physician VAS) After 12 Weeks of Treatment Day 85
A reduction from baseline (i.e., a negative change from baseline) in physician global VAS assessment score indicates improvement in patients. 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 12 weeks (Day 85)
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CDZ173 | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (Physician VAS) After 12 Weeks of Treatment Day 85 | -10.06 total score on a scale | Standard Error 6.584 |
| Placebo | Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (Physician VAS) After 12 Weeks of Treatment Day 85 | 0.91 total score on a scale | Standard Error 7.699 |
95% CI: [-30.94, 9]
Secondary
Change From Baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) After 12 Weeks of Treatment Day 85
The ESSDAI is an established disease outcome measure for Sjögren's syndrome. 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. A reduction from baseline (i.e., a negative change from baseline) in the ESSDAI score is indicative of improvement in a patient.). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity).
Time frame: Baseline and 12 weeks (Day 85)
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CDZ173 | Change From Baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) After 12 Weeks of Treatment Day 85 | -2.82 total score on scale | Standard Error 1.165 |
| Placebo | Change From Baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) After 12 Weeks of Treatment Day 85 | -3.34 total score on scale | Standard Error 1.168 |
95% CI: [-2.52, 3.55]
Secondary
Change From Baseline in the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85
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 12 weeks (Day 85)
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CDZ173 | Change From Baseline in the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85 | Physical Component Summary Score | 4.82 total score on a scale | Standard Error 2.235 |
| CDZ173 | Change From Baseline in the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85 | Mental Component Summary Score | 5.43 total score on a scale | Standard Error 3.415 |
| Placebo | Change From Baseline in the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85 | Physical Component Summary Score | 4.42 total score on a scale | Standard Error 2.425 |
| Placebo | Change From Baseline in the Short Form (36) Health Survey (SF-36) After 12 Weeks of Treatment Day 85 | Mental Component Summary Score | 1.10 total score on a scale | Standard Error 3.792 |
95% CI: [-6.08, 6.89]
95% CI: [-5.27, 13.93]
Secondary
Change in Baseline in Multidimensional Fatigue Inventory (MFI) After 12 Weeks of Treatment (Day 85)
The Multidimensional Fatigue Inventory (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. The reported total score has a range from 20-100, higher scores are associated with greater fatigue.
Time frame: Baseline and 12 weeks (Day 85)
Population: PD analysis set - All randomized patients in the CDZ173 group (20 patients) and placebo group (10 patients) were included in the PD analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CDZ173 | Change in Baseline in Multidimensional Fatigue Inventory (MFI) After 12 Weeks of Treatment (Day 85) | -8.80 total score on scale | Standard Error 5.557 |
| Placebo | Change in Baseline in Multidimensional Fatigue Inventory (MFI) After 12 Weeks of Treatment (Day 85) | -2.25 total score on scale | Standard Error 5.774 |
95% CI: [-21.76, 8.66]