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Comparison of Secukinumab Versus Guselkumab in Clearing Psoriatic Plaques Refractory to Ustekinumab (ARROW)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03553823
Recruitment Status : Completed
First Posted : June 12, 2018
Last Update Posted : August 20, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 15, 2018
First Posted Date  ICMJE June 12, 2018
Last Update Posted Date August 20, 2020
Actual Study Start Date  ICMJE January 14, 2019
Actual Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2018)
Proportion of subjects whose plaque achieves "clear" or "almost clear" status (TCS = 0-2) [ Time Frame: 16 week ]
To demonstrate the superiority of secukinumab over guselkumab in controlling clinical activity in psoriatic plaques resistant to treatment with ustekinumab
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: August 18, 2020)
  • EXPLORATORY: Change from Baseline to Week 16 in epidermal thickness of lesional skin biopsies [ Time Frame: Week 16 ]
    Compare the effect of secukinumab versus guselkumab on the microscopic morphology of the skin plaque
  • EXPLORATORY: Change from Baseline to Week 16 in the number of Ki-67/K-16 positive cells in skin biopsies [ Time Frame: Week 16 ]
    Compare the effect of secukinumab versus guselkumab on the microscopic morphology of the skin plaque
  • EXPLORATORY: Change from Baseline to Week 16 in the number of infiltrating cells expressing IL 17A and IL-23R of lesional skin biopsies and difference from the Baseline non-lesional skin biopsy [ Time Frame: Week 16 ]
    To compare the effect of secukinumab versus guselkumab on the number of IL-17A and IL-23R positive immune cells infiltrating the skin plaque
  • EXPLORATORY: Change from Baseline to Week 16 in the number of different immune cell types in the inflammatory infiltrate of lesional skin biopsies and difference from the Baseline non-lesional skin biopsy [ Time Frame: Week 16 ]
    compare the effects of secukinumab versus guselkumab on the composition of inflammatory infiltrate in the skin plaque
Original Other Pre-specified Outcome Measures
 (submitted: May 30, 2018)
  • Change from Baseline to Week 16 in epidermal thickness of lesional skin biopsies [ Time Frame: Week 16 ]
    Compare the effect of secukinumab versus guselkumab on the microscopic morphology of the skin plaque
  • Change from Baseline to Week 16 in the number of Ki-67/K-16 positive cells in skin biopsies [ Time Frame: Week 16 ]
    Compare the effect of secukinumab versus guselkumab on the microscopic morphology of the skin plaque
  • Change from Baseline to Week 16 in the number of infiltrating cells expressing IL 17A and IL-23R of lesional skin biopsies and difference from the Baseline non-lesional skin biopsy [ Time Frame: Week 16 ]
    To compare the effect of secukinumab versus guselkumab on the number of IL-17A and IL-23R positive immune cells infiltrating the skin plaque
  • Change from Baseline to Week 16 in the number of different immune cell types in the inflammatory infiltrate of lesional skin biopsies and difference from the Baseline non-lesional skin biopsy [ Time Frame: Week 16 ]
    compare the effects of secukinumab versus guselkumab on the composition of inflammatory infiltrate in the skin plaque
 
Descriptive Information
Brief Title  ICMJE Comparison of Secukinumab Versus Guselkumab in Clearing Psoriatic Plaques Refractory to Ustekinumab
Official Title  ICMJE A 16-week Randomized, Open-label, Multicenter Study to Assess the Superiority of Secukinumab Over Guselkumab in the Complete Treatment of Ustekinumab Resistant Psoriatic Plaques
Brief Summary The aim of this study is to describe the effect of direct IL-17A inhibition with secukinumab as compared with the selective inhibition of IL-23 with guselkumab (p19 subunit blocker) in controlling inflammation in psoriatic plaques that remain active despite treatment with the non-selective IL-23 inhibitor ustekinumab (blocker of p40 subunit, shared by IL-12 and IL 23).
Detailed Description This is a 16-week, randomized, open-label, parallel-group, active-control, Phase 2a study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab. Forty subjects will be randomized 1:1 and treated for 16 weeks. In each patient, a target active refractory skin plaque (TCS ≥6) will be described and biopsied at baseline and at study end. The objective of the study is to assess the superiority of secukinumab over guselkumab in achieving clear/almost clear status (TCS 0-2) of the target plaques and describe the molecular mechanisms behind this difference
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a 16-week, randomized, open-label, parallel-group, active-control study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab.
Masking: Single (Outcomes Assessor)
Masking Description:
Blinded outcome assessor will assess subjects on each visit for target plaque TCS, PASI, IGA, BSA, ppIGA, PSSI, NAPS.
Primary Purpose: Treatment
Condition  ICMJE Chronic Plaque-type Psoriasis
Intervention  ICMJE Procedure: Skin biopsies
At Baseline, two 6-mm punch biopsies was taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy was taken from the same area of the active plaque sampled at Baseline.
Study Arms  ICMJE
  • Experimental: secukinumab
    20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive
    Intervention: Procedure: Skin biopsies
  • Active Comparator: Guselkumab
    20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.
    Intervention: Procedure: Skin biopsies
Publications * Not Provided

*   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: May 30, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 28, 2020
Actual Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Chronic plaque-type psoriasis considered inadequately controlled after treatment with ustekinumab according to the following criteria-:

  • Ustekinumab administered at a dose equal or higher than that on the label for at least 24 weeks. The last administration must be at least 12 weeks before randomization
  • absolute PASI score of 1-10 at Screening
  • Presence of at least 1 refractory skin plaque, defined by a TCS of at least 6 and severity score of at least 2 or 3 (moderate) for each individual item, with an area ≥ 10 cm2 at screening.

Exclusion Criteria:

  • Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at Screening or Baseline
  • Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at Baseline
  • Previous treatment with more than one TNFα inhibitor or with IL-17A (including secukinumab), IL-17R or IL-23 (including guselkumab) inhibitors
  • Use of other investigational drugs within 4 weeks before enrolment, or within a period of 5 half lives of enrollment/initiation of the study treatment, whichever is longer
  • Ongoing use of prohibited treatments (see Section 6.2.2)
  • Known immunosuppression (e.g., AIDS) at Screening
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 Canada,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03553823
Other Study ID Numbers  ICMJE CAIN457A2403
2018-001048-70 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
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 August 2020

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