Psoriatic Arthritis
Conditions
Keywords
PsA, immune-mediated chronic inflammatory disease, spondylarthritis, SpA, inflammatory musculoskeletal disease, China bridging study, AIN457, secukinumab
Brief summary
The purpose of this study was to assess the efficacy and safety of secukinumab in Chinese participants with active Psoriatic arthritis (PsA ) compared to placebo.
Detailed description
This study used a randomized, double-blind, placebo-controlled, parallel-group design. A screening period running up to 10 weeks before randomization was used to assess participant eligibility followed by 52 weeks of treatment. A follow-up visit was done 12 weeks after last study treatment administration for all participants, regardless of whether they completed the entire study as planned or discontinued prematurely. At Baseline, the patients fulfilling the inclusion criteria were randomized to one of the following two groups. Group 1 : Secukinumab Dose level 1 s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 Group 2 : Secukinumab Placebo s.c. at BSL, Week 1, 2, 3, 4, 8, and 12. At Week 16, participants in Group 1 and Group 2 were to be re-randomized separately in a 1:1 ratio to receive secukinumab 150 mg or secukinumab 300 mg. The duration of the entire treatment period was 52 weeks. The primary objective was to demonstrate the treatment effect of secukinumab in Chinese subjects with active PsA by assessing American College of Rheumatology rresponse 20 (ACR20 response) rates at Week 16.
Interventions
DRUGAIN457
Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection
OTHERSecukinumab Placebo
Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection
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 99 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed. * Chinese male or non-pregnant, non-lactating Chinese female participants at least 18 years of age. * Diagnosis of PsA classified by Classification of Psoriatic Arthritis (CASPAR) criteria and with symptoms for at least 6 months with moderate to severe Psoriatic arthritis (PsA). * Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening. * Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a documented history of plaque psoriasis. * Participants on Methotrexate (MTX) must be on folic acid supplementation at randomization. * Participants who are on a DMARD other than MTX must discontinue the DMARD 4 weeks prior to randomization visit except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine washout has been performed.
Exclusion criteria
* Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician * Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine). * Previous exposure to secukinumab or other biologic drug directly targeting interleukin- 17 (IL-17) or IL-17 receptor * Participants who have ever received biologic immunomodulating agents except for those targeting Tumor necrosis factor alpha (TNFα). * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception during the entire study (during the entire study).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACR20 Response at Week 16 | 16 weeks | Assessed the efficacy of secukinumab relative to placebo at week 16 using Non-responder imputation (NRI) and based on the percentage of participants achieving an ACR20 response (ACR = American College of Rheumatology). ACR20 response criteria is response ≥ 20% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (Visual Analog Scale (VAS)), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), and High-sensitivity C-reactive protein (hsCRP) or Erythrocyte sedimentation rate (ESR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACR50 Response at Week 16 | 16 weeks | To assess the effect of secukinumab versus placebo on the composite endpoint ACR50 response and based on the percentage of participants achieving an ACR50 response at Week 16 using NRI. ACR50 response criteria is response ≥ 50% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (VAS), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), HAQ-DI, and hsCRP or ESR. |
| Change From Baseline in DAS28-CRP Scores Using Mixed Model Repeated Scores (MMRM) at Week 16 | 16 weeks | To assess the effect of secukinumab versus placebo on change from BSL in DAS28-CRP. The assessment is based on the reduction in DAS28-CRP score. The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment of Disease Activity. The range of DAS28 score is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome. |
| Change From Baseline in PASDAS Scores Using MMRM at Week 16 | 16 weeks | To assess the the effect of secukinumab versus placebo on change from Baseline in PASDAS. Assessment was based on reduction in PASDAS score. PASDAS is a measure of disease activity based on Patient reported measures (excluding mental component score (MCS) of the medical outcomes survey Short Form-36 (SF-36-PCS)), skin, peripheral joint counts (Tender and Swollen joint counts), Dactylitis (LDI), Enthesitis (LEI), acute phase response (CRP) and Patient & Physician global VAS scores. The range of PASDAS is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome. |
| Change From Baseline in SF36-PCS Scores Using MMRM at Week 16 | 16 weeks | To assess the effect of secukinumab versus placebo on change from Baseline in SF-36 PCS. The SF-36 is a widely used and extensively studied instrument to measure HRQoL among healthy participants and participants with acute and chronic conditions. Two overall summary scores, the Physical Component Score (PCS) and the Mental Component Score (MCS) also can be computed. SF36-PCS was used in this study. The range of SF36-PCS score is 0-100. Higher score means better health status. Negative change from baseline indicates a unfavorable outcome. |
| Change From Baseline in HAQ-DI Scores Using MMRM at Week 16 | 16 weeks | To assess the effect of secukinumab versus placebo on change from Baseline in HAQ-DI. Assessment was based on improvement in HAQ-DI PCS scores. The HAQ-DI© is one of the most widely used measures to assess the long-term influence of chronic disease on a participant's level of functional ability and activity restriction, and calculated based on HAQ-DI questionnaire. There are 20 questions in eight categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The range of score is 0-3. Higher score means more severe disability. Negative change from baseline indicates a favorable outcome. |
Countries
China
Participant flow
Recruitment details
In the 1st 16 weeks of study, the 41 participants enrolled were randomized to 2 groups: 1 group received secukinumab 150 mg & the other received placebo. At week 16, the participants were re-randomized within each group for a total of 4 groups. Within the secukinumab group, 1 group continued to receive secukinumab 150 mg while the other half received secukinumab 300 mg. In the Placebo group, 1 group switched to secukinumab 150 mg while the other half switched to secukinumab 300 mg.
Pre-assignment details
This study was conducted in 12 centers in China.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 150 mg (Group 1) Participants received 150 mg dose (dose level 1) of Secukinumab | 20 |
| Placebo of Study Drug (Group 2) Participants received Placebo of the study drug | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 2 (From Week 16) | Participant decision | 0 | 0 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Secukinumab 150 mg (Group 1) | Placebo of Study Drug (Group 2) | Total |
|---|---|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 9.7 | 45.7 years STANDARD_DEVIATION 10.46 | 44.0 years STANDARD_DEVIATION 10.11 |
| Race/Ethnicity, Customized Chinese | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 16 Participants | 23 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 | 0 / 30 | 0 / 21 | 0 / 41 | 0 / 21 |
| other Total, other adverse events | 27 / 30 | 16 / 21 | 37 / 41 | 16 / 21 |
| serious Total, serious adverse events | 0 / 30 | 1 / 21 | 1 / 41 | 0 / 21 |
Outcome results
Primary
ACR20 Response at Week 16
Assessed the efficacy of secukinumab relative to placebo at week 16 using Non-responder imputation (NRI) and based on the percentage of participants achieving an ACR20 response (ACR = American College of Rheumatology). ACR20 response criteria is response ≥ 20% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (Visual Analog Scale (VAS)), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), and High-sensitivity C-reactive protein (hsCRP) or Erythrocyte sedimentation rate (ESR).
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg (Group 1) | ACR20 Response at Week 16 | 14 Participants |
| Placebo of Study Drug (Group 2) | ACR20 Response at Week 16 | 6 Participants |
95% CI: [10.87, 68.95]Regression, Logistic
Secondary
ACR50 Response at Week 16
To assess the effect of secukinumab versus placebo on the composite endpoint ACR50 response and based on the percentage of participants achieving an ACR50 response at Week 16 using NRI. ACR50 response criteria is response ≥ 50% improvement based on: Swollen Joint Count (SJC)/Tender Joint Count (TJC), Patient's global assessment of disease activity (PaGA) (VAS), Physician's global assessment of disease activity (PhGA) (VAS), Patient's assessment of PsA pain intensity (VAS), HAQ-DI, and hsCRP or ESR.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 150 mg (Group 1) | ACR50 Response at Week 16 | 3 Participants |
| Placebo of Study Drug (Group 2) | ACR50 Response at Week 16 | 1 Participants |
95% CI: [-7.18, 30.91]Regression, Logistic
Secondary
Change From Baseline in DAS28-CRP Scores Using Mixed Model Repeated Scores (MMRM) at Week 16
To assess the effect of secukinumab versus placebo on change from BSL in DAS28-CRP. The assessment is based on the reduction in DAS28-CRP score. The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment of Disease Activity. The range of DAS28 score is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned. This is subset of participants from the randomized set to whom study treatment had been assigned and had a valid value of the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg (Group 1) | Change From Baseline in DAS28-CRP Scores Using Mixed Model Repeated Scores (MMRM) at Week 16 | -1.47 scores on a scale | Standard Error 0.206 |
| Placebo of Study Drug (Group 2) | Change From Baseline in DAS28-CRP Scores Using Mixed Model Repeated Scores (MMRM) at Week 16 | -0.37 scores on a scale | Standard Error 0.2 |
95% CI: [-1.68, -0.52]Mixed Models Analysis
Secondary
Change From Baseline in HAQ-DI Scores Using MMRM at Week 16
To assess the effect of secukinumab versus placebo on change from Baseline in HAQ-DI. Assessment was based on improvement in HAQ-DI PCS scores. The HAQ-DI© is one of the most widely used measures to assess the long-term influence of chronic disease on a participant's level of functional ability and activity restriction, and calculated based on HAQ-DI questionnaire. There are 20 questions in eight categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The range of score is 0-3. Higher score means more severe disability. Negative change from baseline indicates a favorable outcome.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned. This is subset of participants from the randomized set to whom study treatment had been assigned and had a valid value of the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg (Group 1) | Change From Baseline in HAQ-DI Scores Using MMRM at Week 16 | -0.31 scores on a scale | Standard Error 0.065 |
| Placebo of Study Drug (Group 2) | Change From Baseline in HAQ-DI Scores Using MMRM at Week 16 | 0.09 scores on a scale | Standard Error 0.063 |
95% CI: [-0.58, -0.21]Mixed Models Analysis
Secondary
Change From Baseline in PASDAS Scores Using MMRM at Week 16
To assess the the effect of secukinumab versus placebo on change from Baseline in PASDAS. Assessment was based on reduction in PASDAS score. PASDAS is a measure of disease activity based on Patient reported measures (excluding mental component score (MCS) of the medical outcomes survey Short Form-36 (SF-36-PCS)), skin, peripheral joint counts (Tender and Swollen joint counts), Dactylitis (LDI), Enthesitis (LEI), acute phase response (CRP) and Patient & Physician global VAS scores. The range of PASDAS is 0-10. Higher score means more active disease. Negative change from baseline indicates a favorable outcome.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned. This is subset of participants from the randomized set to whom study treatment had been assigned and had a valid value of the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg (Group 1) | Change From Baseline in PASDAS Scores Using MMRM at Week 16 | -2.20 scores on a scale | Standard Error 0.245 |
| Placebo of Study Drug (Group 2) | Change From Baseline in PASDAS Scores Using MMRM at Week 16 | -0.55 scores on a scale | Standard Error 0.237 |
95% CI: [-2.35, -0.94]Mixed Models Analysis
Secondary
Change From Baseline in SF36-PCS Scores Using MMRM at Week 16
To assess the effect of secukinumab versus placebo on change from Baseline in SF-36 PCS. The SF-36 is a widely used and extensively studied instrument to measure HRQoL among healthy participants and participants with acute and chronic conditions. Two overall summary scores, the Physical Component Score (PCS) and the Mental Component Score (MCS) also can be computed. SF36-PCS was used in this study. The range of SF36-PCS score is 0-100. Higher score means better health status. Negative change from baseline indicates a unfavorable outcome.
Time frame: 16 weeks
Population: Full Analysis Set (FAS): All participants from the randomized set to whom study treatment had been assigned. This is subset of participants from the randomized set to whom study treatment had been assigned and had a valid value of the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 150 mg (Group 1) | Change From Baseline in SF36-PCS Scores Using MMRM at Week 16 | 4.28 scores on a scale | Standard Error 1.154 |
| Placebo of Study Drug (Group 2) | Change From Baseline in SF36-PCS Scores Using MMRM at Week 16 | 0.08 scores on a scale | Standard Error 1.113 |
95% CI: [0.94, 7.46]Mixed Models Analysis