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Clinical Trial
. 2024 Aug 1;160(8):856-864.
doi: 10.1001/jamadermatol.2024.2131.

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial

Andrew Blauvelt  1 , Emma Guttman-Yassky  2 , Charles Lynde  3 , Saakshi Khattri  2 , Joel Schlessinger  4 , Shinichi Imafuku  5 , Yayoi Tada  6 , Akimichi Morita  7 , Marni Wiseman  8 , Bartlomiej Kwiek  9 , Martina Machkova  10 , Peijin Zhang  11 , Misti Linaberry  11 , Jie Li  11 , Sandra Zhang  11 , Giovanni Franchin  11 , Edgar D Charles  11 , Claudia H M C De Oliveira  11 , Jonathan I Silverberg  12
Affiliations
Clinical Trial

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial

Andrew Blauvelt et al. JAMA Dermatol. .

Abstract

Importance: Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases.

Objective: To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD.

Design, setting, and participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023.

Interventions: Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo.

Main outcome and measure: Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo.

Results: Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo.

Conclusions and relevance: The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT04800315.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Blauvelt reported serving as a speaker for Eli Lilly and Company and UCB; serving as a scientific adviser for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Celldex, CTI BioPharma, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Lipidio, Microbion, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Paragon, Pfizer, Q32 Bio, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Ventyx, Vibliome, and Xencor; serving as a clinical study investigator for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, DermBiont, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, UCB Pharma, and Ventyx; and owning stock in Lipidio and Oruka. Dr Guttman-Yassky reported medical writing for BMS during the conduct of the study as well as grants from Boehringer Ingelheim, Leo Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol Meyers Squibb, Aslan, Regeneron, Anaptysbio, Concert, and Janssen paid to their institutiton and personal fees from Abbvie, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics Limited, Artax Biopharma Inc, AstraZeneca, Bristol Meyers Squibb, Boerhinger-Ingelhiem, Cara Therapeutics, Centrexion Therapeutics Corporation, Connect Biopharm, Eli Lilly, Enveda Biosciences, Escient Pharmaceuticals Inc, Fairmount Funds Management LLC, FL2022-001 Inc, Galderma, Gate Bio, Google Ventures, GSK Immunology, Horizon Therapeutics USA Inc, Incyte, Inmagene, Janssen Biotech, Japan Tobacco, Jasper Therapeutics, Kyowa Kirin, Leo Pharma, Merck, Nektar Therapeutics, Novartis Pharmaceuticals Corporation, NUMAB Therapeutics AG, OrbiMed Advisors LLC, OTSUKA Pfizer, Pharmaxis Ltd, Pioneering Medicine VII, Inc, Proteologix US Inc, RAPT, Regeneron Pharmaceuticals, RibonTherapeutics Inc, Sanofi, SATO, Schrödinger Inc, Sun Pharma Advanced Research Company, Teva Branded Pharmaceutical Products R&D Inc, and UCB outside the submitted work. Dr Lynde reported personal fees from AbbVie, Amgen, Aralez, Bausch Health, Arcutis, Bayer, BioJAMP , Boehringer Ingelheim, personal fees from Bristol Myers Squibb Honoraria, Investigator, Celgene, CeraVe, Cipher, Dermavant, Eli Lilly, Frenius Kabi, Galderma, GSK, InCyte, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma , L’Oreal, Medexus, MedX, Merck, Naos, Moonlake, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, SkinCeuticals, SkinBetterScience, SunPharma, Takeda, TEVA, Tribute, UCB, Viatris, and Volo Health Honoraria during the conduct of the study. Dr Khattri reported grants from and advisory board service for BMS during the conduct of the study. Dr Imafuku reported personal fees from Bristol Myers Squibb during the conduct of the study as well as personal fees from AbbVie, Eisai, Janssen, Amgen, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, Novartis, and UCB and grants from Kyowa Kirin, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, and Torii Yakuhin outside the submitted work. Dr Morita reported personal fees from AbbVie, AYUMI Pharmaceutical, Boehringer Ingelheim Japan, Celgene, Eisai, Eli Lilly Japan, Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and Ushio; grants from AbbVie, Eisai, Eli Lilly Japan, Kyowa Hakko Kirin, Leo Pharma, Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma, Taiho Pharmaceutical, and Torii Pharmaceutical; and consulting fees from AbbVie, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene, Eli Lilly Japan, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma, NPO Health Institute Research of Skin, Pfizer Japan, Sun Pharma, Torii Pharmaceutical, and UCB Japan outside the submitted work. Dr Wiseman reported participating in a clinical trial with Wiseman Dermatology during the conduct of the study. Dr Kwiek reported personal fees from BMS during the conduct of the study as well as personal fees from Pfizer, AbbVie, Leo Pharma, Amgen, Arcutis Biotherapeutics, Novartis, Janssen Pharmaceuticals, Regeneron, Galderma, Allmiral, and Incyte outside the submitted work. Drs Linaberry and Franchin reported being employees of BMS during the conduct of the study. Dr Charles reported being an employee of and owning stock ing Bristol Myers Squibb. Dr Silverberg reported personal fees from AbbVie, Alamar, Aldena, Amgen, AObiome, Apollo, Arcutis, Arena, Asana, Aslan, Attovia, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristell-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, FIDE, Galderma, GlaxoSmithKline, Incyte, Invea, Kiniksa, Leo Pharma, Merck, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, TARGET-RWE, Teva, Union, and UpToDate and grants from Galderma, Incyte, and Pfizer during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Patient Disposition
aDiscontinued treatment because of the COVID-19 pandemic.
See this image and copyright information in PMC

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