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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
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
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
 (submitted: June 10, 2019)
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
 (submitted: March 30, 2015)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
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
 (submitted: March 30, 2015)
  • American College of Rheumatology 50 (ACR50) response at Week 24 [ Time Frame: Week 0- 24 ]
    ACR50 response at Week 24
  • Van der Heijde modified total Sharp score at Week 24. The SvH method includes, in each hand and foot, evaluations of areas for erosions and areas for joint space narrowing [ Time Frame: Week 0- 24 ]
    Change from baseline in van der Heijde modified total Sharp score at Week 24
  • Health assessment questionnaire disability index© (HAQ-DI©) score at Week 24 [ Time Frame: Week 0-24 ]
    Change from baseline in HAQ-DI© score at Week 24
  • Dactylitis at Week 24 [ Time Frame: Week 0-24 ]
    Presence of dactylitis at Week 24
  • Enthesitis at Week 24 [ Time Frame: Week 0-24 ]
    Presence of enthesitis at Week 24
  • Psoriasis Area and Severity Index 75 (PASI75) response at Week 24 [ Time Frame: Week 0-24 ]
    PASI75 response at Week 24
  • Disease Activity Score 28 Joints (DAS28-CRP) at Week 24 [ Time Frame: Week 0-24 ]
    Change from baseline in DAS28-CRP at Week 24
  • Short Form 36 Health Survey (SF36) physical component score at Week 24 [ Time Frame: Week 0-24 ]
    Change from baseline in SF36 physical component score at Week 24
  • Psoriasis Area and Severity Index 90 (PASI90) response at Week 24 [ Time Frame: Week 0-24 ]
    PASI90 response at Week 24
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
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.
Detailed Description

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:

  • Group 1 - secukinumab 150 mg s.c. without loading regimen
  • Group 2 - secukinumab 150 mg s.c. with loading dose regimen
  • Group 3 - secukinumab 300 mg s.c. with loading dose regimen
  • Group 4 - Placebo s.c. NOTE: Group 4 is split into 2 treatment arms, detailed description below. At randomization, subjects will be stratified on the basis of previous anti-TNF therapy as TNFα inhibitor naïve (TNF-naïve) or TNFα inhibitor inadequate responders (TNF-IR).

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):

  • Subjects who are non-responders will receive either secukinumab 150 mg or 300 mg s.c. every 4 weeks starting at Week 16 (as dictated by treatment sequence assigned to these subjects at BSL).
  • Subjects who are responders will continue to receive placebo every 4 weeks. Starting Week 24, these subjects 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 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
  • Experimental: Secukinumab 150 mg load (Group 1)

    Secukinumab 150 mg sc injection every week for 4 weeks followed by Secukinumab 150 mg every 4 weeks for 100 weeks

    Beginning at Week 52, for subjects whose signs and symptoms are not fully controlled, and who the investigator believes may improve further with an increase in dose, may have the secukinumab dose increased to 300mg s.c. every 4 weeks.

    Intervention: Biological: Secukinumab
  • Experimental: Secukinumab 150 mg no load (Group 2)

    Secukinumab 150 mg sc injection every 4 weeks for 100 weeks

    Beginning at Week 52, for subjects whose signs and symptoms are not fully controlled, and who the investigator believes may improve further with an increase in dose, may have the secukinumab dose increased to 300mg s.c. every 4 weeks.

    Intervention: Biological: Secukinumab
  • Experimental: Secukinumab 300 mg load (Group 3)
    Secukinumab 300 mg sc injection every week for 4 weeks followed by Secukinumab 300 mg every 4 weeks for 100 weeks
    Intervention: Biological: Secukinumab
  • Placebo Comparator: Placebo arm 1 (Group 4)

    Placebo to Secukinumab sc injection every week for 4 weeks followed by placebo to Secukinumab every 4 weeks until week 16. Non-responders will be switched to Secukinumab either 150 or 300 mg sc injection every two weeks until week 100. Responders at week 16 will continue receiving placebo until week 24, then will be switched to secukinumab 150 or 300 mg sc injection every 4 weeks for 100 weeks. PLEASE NOTE: Placebo arms 1 and 2 belong to the same placebo group (group 4)

    Beginning at Week 52, for subjects whose signs and symptoms are not fully controlled, and who the investigator believes may improve further with an increase in dose, may have the secukinumab dose increased to 300mg s.c. every 4 weeks.

    Intervention: Biological: Secukinumab
  • Placebo Comparator: Placebo arm 2 (Group 4)

    Placebo to Secukinumab sc injection every week for 4 weeks followed by placebo to Secukinumab every 4 weeks until week 16. Non-responders will be switched to Secukinumab either 150 or 300 mg sc injection every two weeks until week 100. Responders at week 16 will continue receiving placebo until week 24, then will be switched to secukinumab 150 or 300 mg sc injection every 4 weeks for 100 weeks. PLEASE NOTE: Placebo arms 1 and 2 belong to the same placebo group (group 4)

    Beginning at Week 52, for subjects whose signs and symptoms are not fully controlled, and who the investigator believes may improve further with an increase in dose, may have the secukinumab dose increased to 300mg s.c. every 4 weeks.

    Intervention: Biological: Secukinumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2019)
997
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2015)
990
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

Inclusion 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 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.

  • Subjects who have been on a TNFα inhibitor must have experienced an inadequate response to previous or current treatment with a TNFα inhibitor given at an approved dose for at least 3 months or have stopped treatment due to safety/tolerability problems after at least one administration of a TNFα inhibitor.
  • Subjects who have previously been treated with TNFα inhibitors (investigational or approved) will be allowed entry into study after appropriate wash-out period prior to randomization

Exclusion Criteria:

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
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
 
Administrative Information
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
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP