A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate the Efficacy at 24 Weeks and to Assess the Long Term Efficacy, Safety and Tolerability up to 5 Years in Patients With Active Psoriatic Arthritis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 397
- Locations
- 1
- Primary Endpoint
- Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria
Study Overview
Brief Summary
This study was to provide 24 - 52 week efficacy, safety and tolerability data to support the registration of the secukinumab (AIN457) prefilled syringe (PFS) for subcutaneous self administration in subjects with active PsA despite current or previous NSAID, DMARD and/or anti-TNFα therapy. An additional 4 years of long-term efficacy and safety data were collected during the post Week 52 period of the study.
Detailed Description
At baseline (BSL), subjects whose eligibility was confirmed were randomized to one of the following four treatment groups.
- 75 mg secukinumab
- 150 mg secukinumab
- 300 mg secukinumab
- Placebo At Week 16, all subjects were classified as responders (≥ 20% improvement from BSL in both tender and swollen joint counts) or non-responders.
Subjects who were randomized to a secukinumab treatment group at baseline were targeted to remain on the same dose for the entire trial.
Subjects who were randomized to placebo at baseline were re-randomized at Week 16 as follows:
Placebo non-responders received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 16.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients eligible for inclusion in this study have to fulfill all of the following criteria:
- •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 at screening
- •Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis
- •Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs
- •Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 24
- •Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52.
Exclusion Criteria
- •Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
- •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
- •Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
- •Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
- •Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. The following wash out periods need to be observed:
- •Oral or topical retinoids 4 weeks
- •Photochemotherapy (e.g. PUVA) 4 weeks
- •Phototherapy (UVA or UVB) 2 weeks
- •Topical skin treatments (except in face, scalp and genital area during screening, only corticosteroids with mild to moderate potency) 2 weeks
- •Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα, investigational or approved
- •Previous treatment with any cell-depleting therapies including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
Arms & Interventions
Secukinumab (AIN457) 75 mg s.c.
Secukinumab 75 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4.
Intervention: Secukinumab (AIN457) (Drug)
Secukinumab (AIN457) 150 mg s.c.
Secukinumab 150 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4.
Intervention: Secukinumab (AIN457) (Drug)
Secukinumab (AIN457) 300 mg s.c.
Secukinumab 300 mg at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4
Intervention: Secukinumab (AIN457) (Drug)
Placebo s.c.
Placebo at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4. Non-responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 16. Responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 24.
Intervention: Secukinumab (AIN457) (Drug)
Placebo s.c.
Placebo at BSL, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4. Non-responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 16. Responder (assessed at Week 16) were re-randomized to receive AIN457 150mg or AIN457 300 mg starting at Week 24.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria
Time Frame: Week 24
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire \[HAQ-DI\] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.
Secondary Outcomes
- Number of Participants Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis(Week 24)
- Number of Participants Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis(Week 24)
- Change From Baseline in DAS28-CRP(Baseline, Week 24)
- Change From Baseline in SF36-Physical Component Score(Baseline, Week 24)
- Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)(Baseline, Week 24)
- Number of Participants Achieving American College of Rheumatology 50 (ACR50) Response Criteria(Week 24)
- Number of Participants With Dactylitis in the Subset of Subjects Who Had Dactylitis at Baseline(Week 24)
- Number of Participants With Enthesitis in the Subset of Subjects Who Had Enthesitis at Baseline(Week 24)