Efficacy at 24 Weeks and Long Term Safety, Tolerability and Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Psoriatic Arthritis (PsA) (FUTURE 1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01392326
First received: July 7, 2011
Last updated: January 5, 2016
Last verified: January 2016

July 7, 2011
January 5, 2016
September 2011
October 2014   (final data collection date for primary outcome measure)
Percent of Patients Achieving ACR20 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
A patient will be considered as improved according the ACR20 criteria if she/he has at least 20 % improvement in the two following measures:Tender joint count,Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR)
Proportion of patients achieving ACR20 response criteria on secukinumab 75 or 150 mg vs. placebo, in the subgroup of patients who are TNFα inhibitor naïve [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01392326 on ClinicalTrials.gov Archive Site
  • Percent of Subjects Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials with end points of psoriasis
  • Percent of Subjects Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    A 90% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis
  • Change From Baseline in DAS28-CRP for Secukinumab 75 or 150 mg [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS-CRP values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS-CRP below the value of 2.6 is interpreted as Remission.DAS28 the DAS-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters, DAS-CRP is calculated as: <math>DAS-CRP=0.56 \times \sqrt{TEN28} + 0.28 \times \sqrt{SW28} + 0.36 \times \ln(CRP+1) + 0.014 \times SA+0.96</math> With: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale betweenn 0 and 100 ("0":no activity, "100": highest activity possible)
  • Change From Baseline in SF36-PCS for Secukinumab 75 or 150 mg [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • Change From Baseline in HAQ-DI for Secukinumab 75 or 150 mg [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    HAQ-DI, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week "Are you able to …" perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled).
  • Percent of Patients Achieving ACR50 Response Criteria on Secukinumab 75 or 150 mg vs. Placebo [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ACR50 = 50 % improvement in at least 3 of the 5 measures( Patient's assessment of pain, Patient's global assessment of disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR) and 50 % improvement in the swollen and tender joint count.
  • Change From Baseline for Joint/Bone Structural Damage (Van Der Heijde Modified Total Sharp Score) for Secukinumab 75 and 150 mg (Pooled Doses) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Measured are 44 joints for erosions: scored 0 to 5 in hands; 0 to 10 in feet;40 joints for joint space narrowing; summed for total score by two experienced readers scored every film blinded to patient identity, treatment, sequence of film. Lower score equals better outcome. With score of zero being normal. Joint structural damage change from baseline at Week 24 using non-parametric ANCOVA, Linear extrapolation. Estimate (for the difference in mean), SE are from a non-parametric ANCOVA model with the change from baseline van der Heijde total modified Sharp score as the dependent variable, treatment and randomization stratum (TNFa status -naive or IR ) as factors, and weight and baseline van der Heijde total modified Sharp score as covariates.
  • Percent of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percent of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) on secukinumab 75 or 150 mg vs. placebo, in the subgroup of subjects who are TNFα inhibitor naïve [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving ACR20 response criteria on secukinumab 75 or 150 mg vs. placebo, in the entire study population [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline for joint/bone structural damage (as measured by the van der Heijde modified total Sharp score) on secukinumab 75 and 150 mg in the subgroup of subjects who are TNFα inhibitor naïve [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving Major Clinical Response (defined as continuous 6-months of ACR70 response during 52 weeks) on secukinumab 75 or 150 mg vs. placebo (as originally randomized), in the subgroup of subjects who are TNFα inhibitor naïve [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy at 24 Weeks and Long Term Safety, Tolerability and Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Psoriatic Arthritis (PsA)
A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Long Term Safety, Tolerability and Efficacy up to 2 Years in Patients With Active Psoriatic Arthritis
This study will assess the efficacy and safety of secukinumab in patients with active psoriatic arthritis who are intolerant to or have had an inadequate response to NSAIDs, DMARDs and / or TNFα inhibitor therapy.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Psoriatic Arthritis
  • Drug: Secukinumab (75 mg)
    Secukinumab (75 mg)
  • Drug: Secukinumab (150 mg)
    Secukinumab (150 mg)
  • Drug: Placebo Comparator
    Placebo Comparator
  • Experimental: Group 1
    Secukinumab (75mg)
    Intervention: Drug: Secukinumab (75 mg)
  • Experimental: Group 2
    Secukinumab (150 mg)
    Intervention: Drug: Secukinumab (150 mg)
  • Placebo Comparator: Group 3
    Intervention: Drug: Placebo Comparator
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé R, Nash P, Pricop L, Yuan J, Richards HB, Mpofu S; FUTURE 1 Study Group. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med. 2015 Oct;373(14):1329-39. doi: 10.1056/NEJMoa1412679.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
606
October 2014
October 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Male or non-pregnant, non-lactating female patients at least 18 years of age
  • 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
  • Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥2cm diameter or nail changes consistent with psoriasis or documented history o plaque psoriasis

Exclusion criteria:

  • Chest X-ray with evidence of ongoing infectious or malignant process
  • Subjects who have previously been treated with more than 3 different TNFα inhibitors
  • Subjects taking high potency opioid analgesics
  • Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα Other protocol-defined inclusion/exclusion criteria may apply
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Czech Republic,   Germany,   Israel,   Italy,   Philippines,   Poland,   Romania,   Russian Federation,   Singapore,   Slovakia,   Thailand,   United Kingdom
Colombia,   Peru,   Taiwan,   Turkey
 
NCT01392326
CAIN457F2306, 2011-000276-34
Yes
Not Provided
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
January 2016

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