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. 2023 May 16:60:102002.
doi: 10.1016/j.eclinm.2023.102002. eCollection 2023 Jun.

Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial

Jonathan I Silverberg  1 , Peter A Lio  2 , Eric L Simpson  3 , Connie Li  4 , Daniel R Brownell  4 , Ioannis Gryllos  4 , Judith Ng-Cashin  4 , Todd Krueger  4 , Victoria R Swaidan  5 , Robin L Bliss  6 , Hyun D Kim  4
Affiliations

Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial

Jonathan I Silverberg et al. EClinicalMedicine. .

Abstract

Background: Topical 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.

Methods: In 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.

Findings: Between 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).

Interpretation: B244 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.

Funding: AOBiome Therapeutics.

Keywords: Ammonia-oxidising bacteria; Anti-inflammatory; Atopic dermatitis; Live biotherapeutic product; Pruritus.

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Conflict of interest statement

JS has received funding from Galderma, Incyte, and Pfizer, has received consulting fees from Abbvie, Alamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, Union, UpToDate, has received honoraria from Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme, and Participated on a Data Safety Monitoring Board or Advisory Board for Kymab. PL has received funding from AbbVie, AOBiome, Eczema Foundation, received royalties from Theraflex AIM, has received consulting fees from AbbVie, Almirall, Amyris, ASLAN, Bristol-Myers Squibb, Burt's Bees, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Dermira, DermVeda, Eli Lilly, Galderma, IntraDerm, Janssen, Johnson & Johnson, Kaleido Biosci, Kimberly Clark, LEO Pharma, Lipidor, L'Oreal, Menlo Therapeutics, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Sonica, Theraplex, UCB, Unilever, has received honoraria from AbbVie, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche- Posay/L'Oreal, MyOR Diagnostics, ParentMD, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, has received travel support from AbbVie, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche- Posay/L'Oreal, MyOR Diagnostics, ParentMD, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, has patents pending from Theraflex AIM, is an unpaid board member of the National Eczema Association, and holds stock or stock options from Codex Labs, LearnSkin/Learn Health, MaskSense, Medable, Micreos, Modernizing Medicine, Yobee Care. ES has received grants from AbbVie, Acrotech Biopharma Inc, Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, 10.13039/100012308National Jewish Health, Leo, Pfizer, Regeneron, Sanofi, and Target RWE, has received consulting fees from Advances in Cosmetic Medical Derm Hawaii LLC, AbbVie, Amgen, AOBiome LLC, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Boehringer Ingelheim USA, Inc., Boston Consulting Group, 10.13039/100002491Bristol Myers Squibb—BMS, Collective Acumen LLC (CA), CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, ExcerptaMedica, FIDE, Forte Bio RX, Galderma, Gesellschaft Z, GlaxoSmithKline, Incyte, Janssen, 10.13039/100004331Johnson & Johnson, 10.13039/100016348Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Merck, MauiDerm, MLG Operating, MJH holding, Pfizer, Physicians World LLC, PRImE, Regeneron, Revolutionizing Atopic Dermatitis Inc, Roivant, Sanofi-Genzyme, Trevi therapeutics, Valeant, Vindico Medical education, WebMD, has received honoraria from AbbVie, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo, Pfizer, Regeneron, Sanofi, Medscape, has received meeting support from FIDE, MauiDerm, and Sanofi-Regeneron, has served on advisory boards for Arena Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo, Pfizer, Regeneron, Sanofi, and has received payments for serving in a leadership or fiduciary role as Chair of Sanofi-Genzyme and Regeneron US Medical Advisory Board, Chair of Research, Scientific Advisory Committee of the 10.13039/100003980National Eczema Association, Chair of Atopic Dermatitis Expert Resource Group for the AAD, Board Member, International Society for Atopic Dermatitis (ISAD), and Executive Member for the international Harmonizing Outcome Measures in Eczema (HOME) Working Group. CL, DB, IG, JNC, TK, and HK are or were employees of AOBiome. CL has received funding for travel from AOBiome, has patents or patents pending as an employee of AOBiome, and holds stock or stock options in AOBiome. DB has received funding for travel from AOBiome, has patents or patents pending as an employee of AOBiome, and holds stock or stock options in AOBiome. IG has patents or patents pending as an employee of AOBiome and holds stock or stock options in AOBiome. TK has received funding for travel from AOBiome, has patents or patents pending as an employee of AOBiome, and holds stock or stock options in AOBiome. VS is an employee of Biorasi, which received payments associated with the execution and design of the reported study. RB is an employee of Veristat. HK has received funding for travel from AOBiome and holds stock or stock options in AOBiome.

Figures

Fig. 1
Fig. 1
Trial Profile. PP population includes all patients in the mITT population without any major protocol deviations that may have an impact on the efficacy assessments, who complete their Week 4 visit, and who administer at least 50% of investigational product (IP). mITT, modified intent-to-treat population. PP, Per protocol population. Figure created with BioRender.
Fig. 2
Fig. 2
Least-squares mean change from baseline for itch and Atopic Dermatitis clinical signs in the modified intent-to-treat population. AD, Atopic dermatitis. OD, Optical density. WI-NRS, Worst itch numerical rating scale. IGA, Investigator global assessment. EASI, Eczema area and severity index.
Fig. 3
Fig. 3
Proportion of patients achieving itch, IGA, and EASI response in the modified intent-to-treat population. Data is shown as percentage of responders. WI-NRS, Worst itch numerical rating scale. IGA, Investigator global assessment. EASI, Eczema area and severity index.
See this image and copyright information in PMC

References

    1. Roekevisch E., Spuls P.I., Kuester D., Limpens J., Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133(2):429–438. - PubMed
    1. McCleary K.K. 2020. Understanding the lived experience of eczema. More than skin deep; pp. 1–100.
    1. Williams H., Robertson C., Stewart A., et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood. J Allergy Clin Immunol. 1999;103:125–138. - PubMed
    1. Chovatiya R., Lei D., Ahmed A., Chavda R., Gabriel S., Silverberg J.I. Clinical phenotyping of atopic dermatitis using combined itch and lesional severity: a prospective observational study. Ann Allergy Asthma Immunol. 2021 Jul;127(1):83–90.e2. - PubMed
    1. Eichenfield L.F., Tom W.L., Chamlin S.L., et al. Guidelines of care for the management of atopic dermatitis: section 1 diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338–351. - PMC - PubMed

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