Efficacy and safety of guselkumab in biologic-naïve patients with active axial psoriatic arthritis: study protocol for STAR, a phase 4, randomized, double-blinded, placebo-controlled trial

Dafna D Gladman, Philip J Mease, Paul Bird, Enrique R Soriano, Soumya D Chakravarty, May Shawi, Stephen Xu, Sean T Quinn, Cinty Gong, Evan Leibowitz, Denis Poddubnyy, Lai-Shan Tam, Philip S Helliwell, Arthur Kavanaugh, Atul Deodhar, Mikkel Østergaard, Xenofon Baraliakos, Dafna D Gladman, Philip J Mease, Paul Bird, Enrique R Soriano, Soumya D Chakravarty, May Shawi, Stephen Xu, Sean T Quinn, Cinty Gong, Evan Leibowitz, Denis Poddubnyy, Lai-Shan Tam, Philip S Helliwell, Arthur Kavanaugh, Atul Deodhar, Mikkel Østergaard, Xenofon Baraliakos

Abstract

Background: Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read.

Methods: The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N = 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0-10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire - Disability Index (HAQ-DI), Investigator's Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints.

Discussion: This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA.

Trial registration: This trial was registered at ClinicalTrials.gov, NCT04929210 , on 18 June 2021.

Protocol version: Version 1.0 dated 14 April 2021.

Keywords: Axial psoriatic arthritis; Guselkumab; IL-23p19; MRI; Psoriatic arthritis; Randomized controlled trial; Sacroiliac joint; Spine inflammation.

Conflict of interest statement

Dafna D. Gladman received grant support from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB and consulting fees from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Philip J. Mease has received research support from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB; consultant fees from AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB; speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Paul Bird received speaker honoraria from AbbVie, Eli Lilly, Gilead, Janssen, MSD, Pfizer, and UCB; served as advisor for Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. Enrique R. Soriano has served as advisor for AbbVie, Janssen, Novartis, and Roche; has received grant/research support from AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB; has served as speaker/received honoraria from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. Soumya D. Chakravarty, Sean T. Quinn, Cinty Gong, and Evan Leibowitz are employees of Janssen Scientific Affairs, LLC, and own stock or stock options in Johnson & Johnson, of which Janssen Scientific Affairs is a wholly owned subsidiary. May Shawi is an employee of Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson and owns stock or stock options in Johnson & Johnson. Stephen Xu is an employee of Janssen Research & Development and owns stock or stock options in Johnson & Johnson, of which Janssen Scientific Affairs is a wholly owned subsidiary. Denis Poddubnyy has received consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, MSD, Novartis, Pfizer, Roche, and UCB and grants from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer. Lai-Shan Tam has received grant/research support from Amgen, Boehringer Ingelheim, Janssen, GlaxoSmithKline, Novartis, and Pfizer, and has acted as a consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, and Sanofi. Philip S Helliwell has received speaker payment from AbbVie, Janssen, and Novartis; consulting fees from Eli Lilly, Galapagos, Janssen, and Pfizer. Arthur Kavanaugh has received consulting fees from AbbVie, Amgen, BMS, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB. Atul Deodhar received consulting fees for participation in Advisory Boards from AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB; Research Grant funding from AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB; and Speaker fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Mikkel Østergaard received research grants from AbbVie, Bristol Myers Squibb, Celgene, and Novartis, and speaker and/or consultancy fees from AbbVie, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB. Xenofon Baraliakos has received consulting fees, grant/research support/speaker support from AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Standard protocol items: recommendation for interventional trials (SPIRIT) figure: trial visits and assessments.
Fig. 2
Fig. 2
STAR study schema. Refer to Fig. 1 for study agent administration and dosing details. The asterisk (*) symbol indicates the following: 12-week safety follow-up (F/U) period begins at W48 after final study drug administration. EE, early escape; F/U, follow-up; GUS, guselkumab; MRI, magnetic resonance imaging; PBO, placebo; PE, primary endpoint; Q4W, every 4 weeks; Q8W, every 8 weeks; R, randomization; SC, subcutaneous; SI, sacroiliac; W, week

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