Arthritis, Psoriatic
Conditions
Keywords
AIN457, psoriatic arthritis, chronic inflammatory disease, loading regimen, secukinumab, self-injection
Brief summary
The purpose of this study was to provide 16-week efficacy, safety and tolerability data versus placebo to support the use of secukinumab 150 mg by subcutaneous (s.c.) self-administration with or without a loading regimen and maintenance dosing using pre-filled syringe (PFS) and to assess efficacy, safety and tolerability up to 2 years in subjects with active PsA despite current or previous NSAID or DMARD therapy
Interventions
BIOLOGICALSecukinumab
Secukinumab 150 mg (1 mL liquid formulation) in pre-filled syringes were supplied by Novartis. Each secukinumab 300 mg dose was given as two sc injections of secukinumab 150 mg.
OTHERPlacebo
Placebo to secukinumab was also available in 1.0 mL liquid formulation in prefilled syringe to match the active drug.
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
* Diagnosis of Psoriatic Arthritis (PsA) classified by ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria. * Rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative. * Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis. * Inadequate control of symptoms with NSAID. * Other protocol-defined inclusion criteria do apply.
Exclusion criteria
* Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process. * Subjects taking high potency opioid analgesics. * Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor. * Ongoing use of prohibited psoriasis treatments / medications. * Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα. * Previous treatment with any cell-depleting therapies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With American College of Rheumatology 20 (ACR20) Response | 16 weeks | The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Disability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16 | week 16 | DAS28-CRP score change from baseline using MMRM up to Week 16. DAS-CRP values range between 2.0 and 10. The higher the score, the higher the disease severity. n: Number of subjects with measures at both baseline and the corresponding post baseline visit. |
| Psoriatic Area and Severity Index 75 (PASI75) | 16 weeks | PASI is a measure of disease activity based on extent of the disease, severity of erythema, scaling and thickness in different body areas affected by psoriasis. PASI75 is an improvement in the PASI score of at least 75% compared to baseline. PASI75 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. PASI75 response using non-responder imputation and rescue penalty up to Week 16 |
| Short Form Health Survey Physical Component Score (SF-36-PCS) | 16 weeks | SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo. The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value. |
| Number of Participants With American College of Rheumatology 50 (ACR50) | 16 weeks | The ACR50 response is defined by at least 50% decrease in the swollen and tender joint count, and at least 50% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR50 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. This table is the ACR50 response using non-responder imputation and rescue penalty up to Week 16 |
| Number of Participants With American College of Rheumatology 20 (ACR20) Response | 4 weeks | The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Diability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, France, Germany, Italy, Poland, Russia, Sweden, United Kingdom, United States
Participant flow
Recruitment details
There were 341 patients originally randomized to one of 2 trearment groups. Seven placebo patients discontinued before week 16 and therefore not switched to treatment. Only 334 patients received secukinumab treatment.
Pre-assignment details
Patients were randomized 1:1:1.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 150 mg Secukinumab 150 mg s.c. with loading: Secukinumab 150 mg at Baseline, Weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | 114 |
| Secukinumab 150 mg No Load Secukinumab 150 mg s.c. without loading: Secukinumab 150 mg at baseline, followed by dosing every four weeks starting at Week 4, with Placebo at Weeks 1, 2 and 3. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | 113 |
| Placebo Placebo to Secukinumab at Baseline, Weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4 until Week 16/24, depending on patients responder status. From Week 16/24, patients were switched to Secukinumab 150 mg every four weeks. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | 107 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 | 2 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 11 | 12 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 1 |
| Overall Study | Subject/Guardian Decision | 6 | 3 | 7 |
Baseline characteristics
| Characteristic | Secukinumab 150 mg | Secukinumab 150 mg No Load | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 48.3 Years STANDARD_DEVIATION 12.17 | 50.4 Years STANDARD_DEVIATION 11.78 | 48.5 Years STANDARD_DEVIATION 12.12 | 49.0 Years STANDARD_DEVIATION 12.03 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 113 Participants | 113 Participants | 107 Participants | 333 Participants |
| Sex: Female, Male Female | 47 Participants | 51 Participants | 43 Participants | 141 Participants |
| Sex: Female, Male Male | 67 Participants | 62 Participants | 64 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 334 | 1 / 136 | 2 / 334 | 1 / 114 |
| other Total, other adverse events | 252 / 334 | 89 / 136 | 267 / 334 | 61 / 114 |
| serious Total, serious adverse events | 47 / 334 | 12 / 136 | 59 / 334 | 5 / 114 |
Outcome results
Primary
Number of Participants With American College of Rheumatology 20 (ACR20) Response
The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Disability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): all subjects from the randomized set to whom study treatment has been assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 47 Participants |
| Secukinumab 150 mg No Load | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 45 Participants |
| Placebo | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 21 Participants |
p-value: 0.000295% CI: [1.66, 5.66]Chi-squared
p-value: 0.000395% CI: [1.76, 5.97]Chi-squared, Corrected
Secondary
Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16
DAS28-CRP score change from baseline using MMRM up to Week 16. DAS-CRP values range between 2.0 and 10. The higher the score, the higher the disease severity. n: Number of subjects with measures at both baseline and the corresponding post baseline visit.
Time frame: week 16
Population: Full Analysis Set (FAS): all subjects from the randomized set to whom study treatment has been assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg | Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16 | -0.98 scores | Standard Error 0.106 |
| Secukinumab 150 mg No Load | Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16 | -0.84 scores | Standard Error 0.106 |
| Placebo | Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16 | -0.21 scores | Standard Error 0.107 |
Secondary
Number of Participants With American College of Rheumatology 20 (ACR20) Response
The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Diability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo
Time frame: 4 weeks
Population: Full Analysis Set (FAS): all subjects from the randomized set to whom study treatment has been assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 33 Participants |
| Secukinumab 150 mg No Load | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 26 Participants |
| Placebo | Number of Participants With American College of Rheumatology 20 (ACR20) Response | 22 Participants |
Secondary
Number of Participants With American College of Rheumatology 50 (ACR50)
The ACR50 response is defined by at least 50% decrease in the swollen and tender joint count, and at least 50% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant \[either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)\]. ACR50 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. This table is the ACR50 response using non-responder imputation and rescue penalty up to Week 16
Time frame: 16 weeks
Population: Full Analysis Set (FAS): all subjects from the randomized set to whom study treatment has been assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg | Number of Participants With American College of Rheumatology 50 (ACR50) | 26 Participants |
| Secukinumab 150 mg No Load | Number of Participants With American College of Rheumatology 50 (ACR50) | 19 Participants |
| Placebo | Number of Participants With American College of Rheumatology 50 (ACR50) | 7 Participants |
Secondary
Psoriatic Area and Severity Index 75 (PASI75)
PASI is a measure of disease activity based on extent of the disease, severity of erythema, scaling and thickness in different body areas affected by psoriasis. PASI75 is an improvement in the PASI score of at least 75% compared to baseline. PASI75 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. PASI75 response using non-responder imputation and rescue penalty up to Week 16
Time frame: 16 weeks
Population: The psoriasis subset included all full analysis set (FAS) patients who had ≥3% of the body surface area (BSA) affected by psoriatic skin involvement at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg | Psoriatic Area and Severity Index 75 (PASI75) | 29 Participants |
| Secukinumab 150 mg No Load | Psoriatic Area and Severity Index 75 (PASI75) | 27 Participants |
| Placebo | Psoriatic Area and Severity Index 75 (PASI75) | 5 Participants |
Secondary
Short Form Health Survey Physical Component Score (SF-36-PCS)
SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo. The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): all subjects from the randomized set to whom study treatment has been assigned.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg | Short Form Health Survey Physical Component Score (SF-36-PCS) | 3.42 scores on a scale | Standard Error 0.5676 |
| Secukinumab 150 mg No Load | Short Form Health Survey Physical Component Score (SF-36-PCS) | 3.44 scores on a scale | Standard Error 0.5678 |
| Placebo | Short Form Health Survey Physical Component Score (SF-36-PCS) | 0.63 scores on a scale | Standard Error 0.586 |