Study to Demonstrate the Efficacy (Including Inhibition of Structural Damage), Safety and Tolerability up to 2 Years of Secukinumab in Active Psoriatic Arthritis (FUTURE5)
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|ClinicalTrials.gov Identifier: NCT02404350|
Recruitment Status : Completed
First Posted : March 31, 2015
Results First Posted : June 28, 2019
Last Update Posted : October 21, 2019
|First Submitted Date ICMJE||March 16, 2015|
|First Posted Date ICMJE||March 31, 2015|
|Results First Submitted Date ICMJE||July 19, 2018|
|Results First Posted Date ICMJE||June 28, 2019|
|Last Update Posted Date||October 21, 2019|
|Actual Study Start Date ICMJE||August 31, 2015|
|Actual Primary Completion Date||August 16, 2017 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Percentage of Participants With Active Psoriatic Arthritis (PsA) Achieving an American College of Rheumatology Response 20 (ACR20) at Week 16 [ Time Frame: Week 16 ]
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 based on tender 78-joint count, swollen 76-joint count and at least 20% improvement in 3 of the following 5 measures: participant's assessment of PsA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, participant's self-assessed disability (Health Assessment Questionnaire Disability Index (HAQ-DI) score), and acute phase reactant evaluated as (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR)).
|Original Primary Outcome Measures ICMJE
||American College of Rheumatology 20 (ACR20) response at Week 24 [ Time Frame: week 0 - 24 ]
The analysis of the primary efficacy variable will be based on the FAS subjects. Primarily, CRP will be used instead of ESR to calculate ACR response; ESR will only be used in the event CRP is missing.
|Current Secondary Outcome Measures ICMJE
||Change From Baseline to Week 24 With Secukinumab Compared With Placebo for Joint/Bone Structural Damage (Using Van Der Heijde Modified Total Sharp Score (mTSS)). [ Time Frame: Baseline, Week 24 ]
PsA modified vdH-mTSS scoring method was used for assessing bone erosion and joint space narrowing (JSN) of joints of hands & feet; that included the second through fifth distal interphalangeal (DIP) joints of each hand. The maximum score for erosions was 5 in the joints of the hands and 10 in the joints of the feet with 0=no erosions, 1=discrete erosion, 2=large erosion not passing the mid-line, and 3=large erosion passing the mid-line. The JSN was scored per: 0=normal, 1=asymmetrical or minimal narrowing up to a maximum of 25%, 2 = definite narrowing with loss of up to 50% of the normal space, 3 = definite narrowing with loss of 50-99% of the normal space, and 4 = absence of a joint space. The maximum total erosion score was 320 (200 for the hands and 120 for the feet),and the maximum total JSN score was 208 (160 for the hands and 48 for the feet). The total radiographic score (hands and feet combined) ranged from 0 to 528, where higher scores indicated more articular damage.
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Study to Demonstrate the Efficacy (Including Inhibition of Structural Damage), Safety and Tolerability up to 2 Years of Secukinumab in Active Psoriatic Arthritis|
|Official Title ICMJE||A Phase III, Randomized, Double-blind, Placebo Controlled Multi-center Study of Subcutaneous Secukinumab (150 mg and 300 mg) in Prefilled Syringe to Demonstrate Efficacy (Including Inhibition of Structural Damage), Safety, and Tolerability up to 2 Years in Subjects With Active Psoriatic Arthritis (FUTURE 5)|
|Brief Summary||The purpose of this study is to demonstrate efficacy including effect on inhibition of progression of structural damage, safety and tolerability up to 2 years with primary focus at Week 16 (week 24 for structural damage), to support the use of secukinumab pre-filled syringe (PFS) by subcutaneous (s.c.) self-administration with or without loading regimen in subjects with active Psoriatic Arthritis (PsA) despite current or previous NSAID, DMARD therapy and/or previous anti-TNFα therapy. Long term efficacy up to 2 years will be based on signs and symptoms of joint/bone structure preservation (X-ray) and improvement in physical function measured by Health Assessment Questionnaire - Disability Index (HAQ-DI©), as well as skin and nail improvement for psoriasis signs.|
This multicenter study uses a randomized, double-blind, placebo-controlled, parallel-group design. A screening period (SCR) running up to 10 weeks before randomization will be used to assess subject eligibility followed by 104 weeks of treatment.
At BSL approximately 990 subjects whose eligibility is confirmed will be randomized to one of four treatment groups in 2:2:2:3 ratio:
At each study treatment visit, one (for secukinumab 150 mg) or two (for secukinumab 300 mg) s.c. injections in the form of PFS will be administered, since secukinumab is available in 1.0 mL (150 mg) PFSs. Placebo to secukinumab is also available in 1.0 mL to match the active drug.
At Week 16, subjects who have been randomized to secukinumab groups at BSL (Groups 1-3) will be classified as either responders (≥20% improvement from BSL in both tender joint count (TJC) and swollen joint counts (SJC)) or non-responders (<20% improvement from BSL TJC or SJC), however they will continue on the same treatment irrespective of their response status.
At Week 16, subjects who have been randomized to placebo at BSL (Group 4) will be classified as either responders (≥20% improvement from BSL in both TJC and SJC) or non-responders (<20% improvement from BSL TJC or SJC):
At Week 24, the assessments to address the primary objective will be performed. As described above, subjects who are still receiving placebo s.c. injection will receive either secukinumab 150 mg s.c. or 300 mg s.c. every 4 weeks starting at Week 24 (as dictated by treatment sequence assigned to these subjects at BSL).
At week 52, based on Investigator's decision, the subjects on a 150 mg doses whose sign and symptoms do not show satisfactory response have the possibility to be allocated to secukinumab 300 mg s.c.
After the Week 52 database lock and analyses have been completed, site personnel and subjects will be unblinded to the original randomized treatment (sequence) assignment at randomization. In addition, treatment will be given open-label in order to eliminate the placebo injection. The subject will continue to receive the same active dose of secukinumab as open-label treatment administered until Week 100.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||Psoriatic Arthritis|
|Intervention ICMJE||Biological: Secukinumab
Anti IL-17a monoclonal antibody
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||January 24, 2019|
|Actual Primary Completion Date||August 16, 2017 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at BSL ≥3 tender joints out of 78 and ≥3 swollen joints out of 76 (dactylitis of a digit counts as one joint each). - 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. - 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 who are regularly taking NSAIDs as part of their PsA therapy are required to be on a stable dose for at least 2 weeks before study randomization and should remain on a stable dose up to Week 24. - 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. - Subjects on MTX must be on folic acid supplementation at randomization. - Subjects 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 wash-out has been performed.
Chest X-ray or chest 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 IL-17 or IL-17 receptor. - Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. - Any intramuscular or intravenous or intra-articular corticosteroid treatment within 4 weeks before randomization. - 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 - Other protocol-defined exclusion criteria do apply
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Argentina, Austria, Canada, Chile, Czechia, Denmark, Estonia, Finland, Germany, Greece, Guatemala, Hungary, India, Ireland, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, Philippines, Russian Federation, Spain, Sweden, Thailand, United Kingdom, United States, Vietnam|
|Removed Location Countries||Czech Republic|
|NCT Number ICMJE||NCT02404350|
|Other Study ID Numbers ICMJE||CAIN457F2342|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||
|Responsible Party||Novartis ( Novartis Pharmaceuticals )|
|Study Sponsor ICMJE||Novartis Pharmaceuticals|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Verification Date||October 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP