Dataset Information

Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.

ABSTRACT:

Introduction

Atopic dermatitis (AD) is a heterogeneous disease, with involvement of the T-helper cell (Th) 2, Th22, and potentially Th17 pathways, supporting the use of interleukin (IL)-23 and IL-22 blockade in AD.

Methods

This phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03706040) evaluated the efficacy and safety of risankizumab, an IL-23 inhibitor, in patients (≥ 12 years old) with moderate-to-severe AD, defined by an Eczema Area and Severity Index (EASI) ≥ 16, affected body surface area ≥ 10%, and a Validated Investigator Global Assessment for AD (vIGA-AD) score ≥ 3. Patients were randomized 2:2:1 to 16-week treatment with risankizumab 150 mg, risankizumab 300 mg, or placebo in period A; patients receiving placebo were re-randomized 1:1 to risankizumab 150 mg or 300 mg and patients receiving risankizumab continued on their randomized dose in 36-week period B. Study drug was administered at baseline and weeks 4, 16, 28, and 40. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction from baseline in EASI (EASI 75) at week 16. Safety was analyzed in all randomized patients who received study medication.

Results

Neither the risankizumab 150 mg (n = 69) nor the 300 mg dose group (n = 69) demonstrated a significantly higher proportion of patients achieving EASI 75 at week 16 compared with the placebo group (n = 34; treatment difference [95% CI] 13.0% [-1.7 to 27.7%; P = 0.084] and 10.0% [-4.6 to 24.6%; P = 0.179], respectively). Most adverse events were mild to moderate in severity; five patients receiving risankizumab reported serious adverse events, including two patients who reported cellulitis.

Conclusions

Risankizumab was generally well tolerated, with no new safety concerns identified. The study's primary endpoint was not met, with no significant difference in the proportion of patients achieving an EASI 75 response at week 16 with risankizumab 150 mg or 300 mg versus placebo.

Trial registration

ClinicalTrials.gov NCT03706040.

SUBMITTER: Tyring SK

PROVIDER: S-EPMC9805909 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.

Tyring Stephen K SK Rich Phoebe P Tada Yayoi Y Beeck Stefan S Messina Izabella I Liu Jie J Huang Xiaohong X Shumack Stephen S

Dermatology and therapy 20230102 2

<h4>Introduction</h4>Atopic dermatitis (AD) is a heterogeneous disease, with involvement of the T-helper cell (Th) 2, Th22, and potentially Th17 pathways, supporting the use of interleukin (IL)-23 and IL-22 blockade in AD.<h4>Methods</h4>This phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03706040) evaluated the efficacy and safety of risankizumab, an IL-23 inhibitor, in patients (≥ 12 years old) with moderate-to-severe AD, defined by an Eczema Area and Severity Ind ...[more]

PMID: 36588137

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Project description:BackgroundTopical anti-inflammatory therapy is a cornerstone of treatment for atopic dermatitis (AD). However, many unmet needs remain with existing therapies. B244 is a live topical biotherapeutic being tested for the reduction of pruritus and improvement of eczema signs in patients with AD. We aimed to assess the safety and efficacy of B244, compared to vehicle, for patients with mild-to-moderate AD and moderate-to-severe pruritus.MethodsIn this randomised, placebo-controlled, double-blind phase 2b trial, adults aged 18-65 years with mild-to-moderate AD and moderate-to-severe pruritus were enrolled across 56 sites in the USA. Patients were randomised 1:1:1 into a low-dose (optical density at 600 nm [OD] 5.0), high-dose (OD 20.0), or vehicle group for the 4-week treatment period and a 4 week follow-up period. Patients were instructed to apply the topical spray twice daily throughout the treatment period. Randomisation was centrally based (random alternating blocks of 6 and 3) and stratified by site. All participants, investigators, and those assessing outcomes were blinded to the treatment group assignments. The primary endpoint was the mean change in pruritus as measured by the Worst Itch Numeric Rating Scale (WI-NRS) at 4 weeks. Safety was tracked throughout the study. Primary efficacy analyses included the modified intent-to-treat (mITT) population, encompassing those who received at least one dose of study drug and attended at least one post-baseline visit. The safety population included all participants who received at least one does of study drug. This study is registered with ClinicalTrials.gov, NCT04490109.FindingsBetween June 4, 2020 and October 22, 2021, 547 eligible patients were enrolled. All study endpoints were meaningfully improved with B244 compared to vehicle. The WI-NRS score was reduced by 34% (-2.8 B244 vs -2.1 placebo, p = 0.014 and p = 0.015 for OD 20.0 and OD 5.0), from a baseline score of >8. B244 was well tolerated with no serious adverse events (SAEs); treatment-emergent adverse events (TEAEs) and treatment related TEAEs were low in incidence, mild in severity, and transient. 33 (18%) of 180 patients given B244 OD 5.0, 29 (16%) of 180 patients given B244 OD 20.0, and 17 (9%) of 186 patients given placebo reported treatment-emergent adverse events; headache was the most frequent (3%, 2%, and 1%, respectively).InterpretationB244 was well tolerated and demonstrated improved efficacy compared to vehicle in all primary, secondary, and exploratory endpoints and should be further developed as a novel, natural, fast-acting topical spray treatment option for AD and associated pruritus.FundingAOBiome Therapeutics.

Project description:ImportanceHidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options.ObjectiveTo evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS.Design, setting, and participantsThis phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline.InterventionsParticipants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10).Main outcomes and measuresThe prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores.ResultsEighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).Conclusions and relevanceIn this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS.Trial registrationClinicalTrials.gov Identifier: NCT03248531.

Dataset Information

Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.

Similar Datasets

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