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

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ClinicalTrials.gov Identifier: NCT03553823
Recruitment Status : Recruiting
First Posted : June 12, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Chronic Plaque-type Psoriasis Procedure: Skin biopsies Phase 2

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  (Clinical Trial)
Estimated Enrollment : 40 participants
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
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
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : August 2, 2019
Estimated Study Completion Date : August 2, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: secukinumab
20 subjects with plaque psoriasis with an inadequate response to ustekinumab will self-administer 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
Procedure: Skin biopsies
At Baseline, two 6-mm punch biopsies will be taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy will be taken from the same area of the active plaque sampled at Baseline.

Active Comparator: Guselkumab
20 subjects with plaque psoriasis with an inadequate response to ustekinumab will self-administer guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.
Procedure: Skin biopsies
At Baseline, two 6-mm punch biopsies will be taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy will be taken from the same area of the active plaque sampled at Baseline.




Primary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03553823


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, South Carolina
Novartis Investigative Site Recruiting
Charleston, South Carolina, United States, 29414
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03553823     History of Changes
Other Study ID Numbers: CAIN457A2403
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: October 2018
Individual Participant Data (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


Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal
Ustekinumab
Immunologic Factors
Physiological Effects of Drugs
Dermatologic Agents