Study of Safety, Tolerability, and Efficacy of Secukinumab in Subjects With Moderate to Severe Palmoplantar Psoriasis (GESTURE)

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Demonstrate the Efficacy at 16 Weeks of Secukinumab 150 and 300 mg s.c. and to Assess Safety, Tolerability and Long-term Efficacy up to 132 Weeks in Subjects With Moderate to Severe Palmoplantar Psoriasis

Purpose of the study was to demonstrate the efficacy of secukinumab versus placebo on palmoplantar psoriasis and to assess the long term efficacy, safety and tolerability of secukinumab.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Palmoplantar Psoriasis
• Intervention / Treatment: Biological: secukinumab 150 mg; Biological: secukinumab 300 mg; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Novartis Investigative Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Novartis Investigative Site
    • East Melbourne, Victoria, Australia, 3002
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2S 3B3
      • Novartis Investigative Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 3H7
      • Novartis Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3Z 2S6
      • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00250 HUS
    • Novartis Investigative Site
  • Tampere, Finland, 33100
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Miskolc, Hungary, 3529
    • Novartis Investigative Site
  • Szeged, Hungary, H-6725
    • Novartis Investigative Site
• Israel
  • Afula, Israel, 1834111
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Tel Aviv, Israel, 64239
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6209804
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3015 CE
    • Novartis Investigative Site
  • CK
    • Breda, CK, Netherlands, 4818
      • Novartis Investigative Site
• Norway
  • Stavanger, Norway, 4068
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649-035
    • Novartis Investigative Site
  • Lisboa, Portugal, 1998 - 018
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
  • Porto, Portugal, 4200 319
    • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • Moscow, Russian Federation, 107076
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119071
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
• Slovakia
  • Kosice, Slovakia, 04011
    • Novartis Investigative Site
  • Svidnik, Slovakia, 089 01
    • Novartis Investigative Site
  • Slovak Republic
    • Kosice-Saca, Slovak Republic, Slovakia, 040 15
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
  • Las Palmas De G.C
    • Las Palmas de Gran Canaria, Las Palmas De G.C, Spain, 35010
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06500
    • Novartis Investigative Site
  • Fatih / Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Gaziantep, Turkey, 27310
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • England
    • London, England, United Kingdom, E11 1NR
      • Novartis Investigative Site
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Novartis Investigative Site
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • Novartis Investigative Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Novartis Investigative Site
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072-2301
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with chronic, moderate to severe plaque type psoriasis for at least 6 months prior to randomization and significant involvement of the palms and soles at baseline, defined as palmoplantar Investigator's Global Assessment (ppIGA) score of ≥ 3 on a 5-point scale, as well as at least one skin plaque at baseline which is not in the palmoplantar area
• Candidates for systemic therapy, i.e. psoriasis inadequately controlled by topical treatment (including super potent topical corticosteroids) and/or phototherapy and/or previous systemic therapy

Exclusion Criteria:

• Forms of psoriasis other than chronic plaque type psoriasis (e.g., pustular psoriasis, palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic and guttate psoriasis)
• Drug-induced psoriasis (e.g. new onset or current exacerbation from β-blockers, calcium channel inhibitors or lithium)
• Ongoing use of prohibited treatments (e.g. topical or systemic corticosteroids (CS), UV therapy). Washout periods do apply.
• Prior exposure to secukinumab (AIN457) or any other biological drug directly targeting IL-17 or the IL-17 receptor
• Use of any investigational drugs within 4 weeks prior to study treatment initiation or within a period of 5 half-lives of the investigational treatment, whichever is longer
• Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy
• History of hypersensitivity to constituents of the study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: secukinumab 150mg; 201 subjects were randomized in a 1:1:1 ratio to secukinumab either 150 mg or 300 mg, or placebo. Subjects assigned to secukinumab 150 mg were dosed weekly for the first five weeks, then every four weeks up to and including Week 128. To maintain blinding, subjects received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment were administered by sub-cutaneous injections.	Biological: secukinumab 150 mg; Study treatment were provided in pre-filled syringes of secukinumab 150 mg in 1 mL. Each dosing consiseds of one secukinumab 150 mg s.c. injection plus one placebo secukinumab s.c. injection and took place once weekly during five weeks (at Baseline, Weeks 1, 2, 3 and 4), then once every four weeks starting at Week 8 until Week 128 inclusive. In order to maintain the blinding, patients also received two placebo injections at Weeks 17, 18 and 19. Patients self-administered study treatment under the supervision of site personnel when injections occur during study visits, or at home otherwise.; Other Names: AIN457 150 mg
Experimental: secukinumab 300 mg; 201 subjects were randomized in a 1:1:1 ratio to secukinumab either 150 mg or 300 mg, or placebo. Subjects assigned to secukinumab 300 mg were dosed weekly for the first five weeks and then every four weeks up to and including Week 128. In order to maintain the blinding, subjects received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment were administered by sub-cutaneous injections.	Biological: secukinumab 300 mg; Study treatment were provided in pre-filled syringes of secukinumab 150 mg in 1 mL. Each dosing consisted of two secukinumab 150 mg s.c. injections and took ke place once weekly during five weeks (at Baseline, Weeks 1, 2, 3 and 4), then once every four weeks starting at Week 8 until Week 128 inclusive. In order to maintain the blinding, patients also receives two placebo injections at Weeks 17, 18 and 19. Patients self-administered study treatment under the supervision of site personnel when injections occur during study visits, or at home otherwise.; Other Names: AIN457 300 mg
Placebo Comparator: Placebo; 201 subjects were randomized in a 1:1:1 ratio to secukinumab either 150 mg or 300 mg, or placebo. Subjects on placebo were dosed weekly for 5 weeks then once every 4 weeks. At Week 16, ppIGA responders continued to receive placebo weekly for 5 weeks starting at Week 16, then every 4 weeks up to and including Week 76 while ppIGA non-responders were randomized in a 1:1 ratio to secukinumab either 150 mg or 300mg weekly for 5 weeks, starting at Week 16, then every 4 weeks up to and including Week 128. At Week 80, subjects on placebo were either terminated their participation, if ppIGA responders, or randomized in a 1:1 ratio to secukinumab either 150 mg or 300 mg once every 4 weeks until Week 128 inclusive. All doses of study treatment were administered by sub-cutaneous injections.	Biological: Placebo; Placebo were provided in 1 mL pre-filled syringes. Each dosing consisted of two s.c. injections and took place once weekly during five weeks (at Baseline, Weeks 1, 2, 3 and 4), then at Week 8 and at Week 12. At Week 16, ppIGA responders continued on placebo with dosing at Weeks 16, 17, 18, 19 and 20, then once every four weeks from Week 24 until Week 76 inclusive. At Week 80, ppIGA responders ended their participation in the study while ppIGA non-responders were re-randomized, to receive 150 mg or 300 mg secukinumab once every four weeks starting at Week 80 until Week 128 inclusive. Patients self-administered study treatment under the supervision of site personnel when injections occur during study visits, or at home otherwise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Participants With Palmoplantar Investigator Global Assessmnet (ppIGA) 0 or 1 Response After 16 Weeks of Treatment	palmoplantar Investigator's Global Assessment (ppIGA) response after 16 weeks of treatment. To be considered a ppIGA responder at Week 16, a subject must have ppIGA of 0 or 1 at Week 16 and a reduction of at least 2 points on the ppIGA scale from baseline.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Participants With Palmoplantar Investigator Global Assessment (ppIGA) 0 or 1 Response - Treatment Period I	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).	Week 1, week 2, week 4, week, 8, week 12, week 16
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Treatment Period II	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).	Week 16, Week 20, Week 28, Week 32, Week 64, Week 132
Percentages of Subjects With ppIGA 0 or 1 Response (Observed Cases) - Entire Treatment Period	ppIGA: Palmoplantar Ivestigator's Global Assessment. The IGA mod 2011 rating scale: The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Based on this scale, a patient was considered as an IGA 0 or 1 responder if they achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).	Week 16, Week 24, Week 28, Week 80
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score -Treatment Period I	Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
Absolute Change From Baseline for Palmoplantar Psoriasis Area and Severity Index (ppPASI) Score (Observed Cases) - Entire Treatment Set	Psoriasis Area and Severity Index (PASI) is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease).	Week 16, Week 32, Week 80, Week 132
Number of Participants Developing Anti-secukinumab Antibodies	To investigate the development of immunogenicity against secukinumab	Over time up to week 132

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2013
• Primary Completion (Actual): November 2, 2016
• Study Completion (Actual): November 2, 2016

Study Registration Dates

• First Submitted: January 23, 2013
• First Submitted That Met QC Criteria: March 5, 2013
• First Posted (Estimate): March 7, 2013

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Skin condition, itching, psoriasis vulgaris, relapsing remitting psoriasis, immune-med systemic disease, skin lesions, scaly patches, papules, plaques
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A2312; 2012-005412-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No