Psoriatic Arthritis
Conditions
Keywords
Psoriatic arthritis, PsA, ACR, CASPAR
Brief summary
This study will assess the efficacy and safety of secukinumab in patients with active psoriatic arthritis who are intolerant to or have had an inadequate response to NSAIDs, DMARDs and / or TNFα inhibitor therapy.
Interventions
Secukinumab (75 mg)
Secukinumab (150 mg)
DRUGPlacebo Comparator
Placebo Comparator
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or non-pregnant, non-lactating female patients at least 18 years of age * Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each) * Rheumatoid factor and anti-CCP antibodies negative * Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥2cm diameter or nail changes consistent with psoriasis or documented history o plaque psoriasis
Exclusion criteria
* Chest X-ray with evidence of ongoing infectious or malignant process * Subjects who have previously been treated with more than 3 different TNFα inhibitors * Subjects taking high potency opioid analgesics * Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | Week 24 | A patient will be considered as improved according the ACR20 criteria if she/he has at least 20 % improvement in the two following measures:Tender joint count,Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | Week 24 | A 90% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis |
| Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg | Week 24 | DAS-CRP values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS-CRP below the value of 2.6 is interpreted as Remission.DAS28 the DAS-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters, DAS-CRP is calculated as: \<math\>DAS-CRP=0.56 \\times \\sqrt{TEN28} + 0.28 \\times \\sqrt{SW28} + 0.36 \\times \\ln(CRP+1) + 0.014 \\times SA+0.96\</math\> With: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale betweenn 0 and 100 (0:no activity, 100: highest activity possible) |
| Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg | Week 24 | The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. |
| Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg | Week 24 | HAQ-DI, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week Are you able to … perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). |
| Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | Week 24 | A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials with end points of psoriasis |
| Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses) | Week 24 | Measured are 44 joints for erosions: scored 0 to 5 in hands; 0 to 10 in feet;40 joints for joint space narrowing; summed for total score by two experienced readers scored every film blinded to patient identity, treatment, sequence of film. Lower score equals better outcome. With score of zero being normal. Joint structural damage change from baseline at Week 24 using non-parametric ANCOVA, Linear extrapolation. Estimate (for the difference in mean), SE are from a non-parametric ANCOVA model with the change from baseline van der Heijde total modified Sharp score as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates. |
| Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline | Week 24 | — |
| Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline | Week 24 | — |
| Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | Week 24 | ACR50 = 50 % improvement in at least 3 of the 5 measures( Patient's assessment of pain, Patient's global assessment of disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR) and 50 % improvement in the swollen and tender joint count. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Germany, Israel, Italy, Philippines, Poland, Romania, Russia, Singapore, Slovakia, Thailand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Secukinumab (75mg) | 202 |
| Group 2 Secukinumab (150 mg) | 202 |
| Group 3 Placebo match (for 75 and 150 mg) | 202 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 6 | 11 |
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 14 | 10 | 15 |
| Overall Study | Lost to Follow-up | 1 | 3 | 4 |
| Overall Study | Physician Decision | 7 | 5 | 2 |
| Overall Study | Pregnancy | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 11 | 15 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 22 Participants | 10 Participants | 54 Participants |
| Age, Categorical Between 18 and 65 years | 180 Participants | 180 Participants | 192 Participants | 552 Participants |
| Sex: Female, Male Female | 118 Participants | 106 Participants | 106 Participants | 330 Participants |
| Sex: Female, Male Male | 84 Participants | 96 Participants | 96 Participants | 276 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 217 / 292 | 222 / 295 | 101 / 202 |
| serious Total, serious adverse events | 32 / 292 | 51 / 295 | 11 / 202 |
Outcome results
Primary
Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo
A patient will be considered as improved according the ACR20 criteria if she/he has at least 20 % improvement in the two following measures:Tender joint count,Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR)
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 50.5 % participant |
| Group 2 | Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 50.0 % participant |
| Group 3 | Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 17.3 % participant |
p-value: <0.000195% CI: [3.46, 8.85]Regression, Logistic
p-value: <0.000195% CI: [3.37, 8.62]Regression, Logistic
Secondary
Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses)
Measured are 44 joints for erosions: scored 0 to 5 in hands; 0 to 10 in feet;40 joints for joint space narrowing; summed for total score by two experienced readers scored every film blinded to patient identity, treatment, sequence of film. Lower score equals better outcome. With score of zero being normal. Joint structural damage change from baseline at Week 24 using non-parametric ANCOVA, Linear extrapolation. Estimate (for the difference in mean), SE are from a non-parametric ANCOVA model with the change from baseline van der Heijde total modified Sharp score as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates.
Time frame: Week 24
Population: .Full analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses) | 0.02 units on a scale | Standard Error 0.22 |
| Group 2 | Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses) | 0.13 units on a scale | Standard Error 0.2 |
| Group 3 | Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses) | 0.57 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg
DAS-CRP values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS-CRP below the value of 2.6 is interpreted as Remission.DAS28 the DAS-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters, DAS-CRP is calculated as: \<math\>DAS-CRP=0.56 \\times \\sqrt{TEN28} + 0.28 \\times \\sqrt{SW28} + 0.36 \\times \\ln(CRP+1) + 0.014 \\times SA+0.96\</math\> With: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale betweenn 0 and 100 (0:no activity, 100: highest activity possible)
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg | -1.67 units on scale | Standard Error 0.085 |
| Group 2 | Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg | -1.62 units on scale | Standard Error 0.084 |
| Group 3 | Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg | -0.77 units on scale | Standard Error 0.123 |
Secondary
Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg
HAQ-DI, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week Are you able to … perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled).
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg | -0.41 units on a scale | Standard Error 0.036 |
| Group 2 | Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg | -0.40 units on a scale | Standard Error 0.036 |
| Group 3 | Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg | -0.17 units on a scale | Standard Error 0.047 |
Secondary
Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg
The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg | 5.41 units on scale | Standard Error 0.524 |
| Group 2 | Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg | 5.91 units on scale | Standard Error 0.525 |
| Group 3 | Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg | 1.82 units on scale | Standard Error 0.715 |
Secondary
Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo
ACR50 = 50 % improvement in at least 3 of the 5 measures( Patient's assessment of pain, Patient's global assessment of disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR) and 50 % improvement in the swollen and tender joint count.
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 30.7 % participant |
| Group 2 | Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 34.7 % participant |
| Group 3 | Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo | 7.4 % participant |
Secondary
Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline | 43.3 % participants |
| Group 2 | Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline | 51.9 % participants |
| Group 3 | Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline | 84.5 % participants |
Secondary
Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline
Time frame: Week 24
Population: Full Analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline | 51.2 % participants |
| Group 2 | Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline | 54.0 % participants |
| Group 3 | Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline | 87.2 % participants |
Secondary
Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline
A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials with end points of psoriasis
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 64.8 % participants acheiving goal |
| Group 2 | Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 61.1 % participants acheiving goal |
| Group 3 | Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 8.3 % participants acheiving goal |
Secondary
Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline
A 90% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 49.1 % of participants acheiving goal |
| Group 2 | Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 45.4 % of participants acheiving goal |
| Group 3 | Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline | 3.7 % of participants acheiving goal |