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

• ClinicalTrials.gov Identifier: NCT03553823
• Recruitment Status: Completed
• First Posted: June 12, 2018
• Last Update Posted: August 20, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: May 15, 2018
• First Posted Date: June 12, 2018
• Last Update Posted Date: August 20, 2020
• Actual Study Start Date: January 14, 2019
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: 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: Comparison of Secukinumab Versus Guselkumab in Clearing Psoriatic Plaques Refractory to Ustekinumab
• Official Title: 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: Interventional
• Study Phase: Phase 2

Study Design

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: Chronic Plaque-type Psoriasis

Intervention

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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 30, 2018): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 28, 2020
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United States

Administrative Information

• NCT Number: NCT03553823
• Other Study ID Numbers: 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

• 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: Novartis Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: August 2020