{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T01:15:51Z","timestamp":1755998151278,"version":"3.37.3"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Timber Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Emollients and keratolytics are frequently used to manage symptoms of congenital ichthyosis (CI). Systemic retinoid treatment is complicated by teratogenicity and dose-limiting adverse effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This analysis from the randomized Phase IIb CONTROL study investigated the characteristics of participants who responded to treatment with TMB-001, a novel topical isotretinoin ointment formulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants \u2265 9\u2005years of age with genetically confirmed CI and \u2265 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with \u2265 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%, TMB-001 0.1% or vehicle, twice daily for 12 weeks. Efficacy endpoints included the proportion of participants with \u2265 50% reduction in VIIS-scaling (VIIS-50) compared with baseline and \u2265 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score compared with baseline. Changes in body surface area (BSA) involvement, Dermatology Life Quality Index (DLQI) scores and Itch-Numeric Rating Scale (I-NRS) scores were assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among the 33 participants (11 randomized to TMB-001 0.05%, 10 to TMB-001 0.1% and 12 to vehicle), median age was 29\u2005years (range 9\u201380), and most were male (64%) and White (79%). Baseline demographics were generally similar among participants who did or did not achieve TMB-001 treatment success. Participants who had lower mean BSA involvement and higher DLQI and I-NRS scores at baseline were more likely to achieve VIIS-50. Similarly, higher baseline DLQI and I-NRS scores were associated with IGA response; BSA involvement was similar for IGA responders vs. nonresponders.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Higher DLQI and I-NRS scores at baseline were associated with participants achieving treatment success by VIIS-50 and IGA response. Lower BSA involvement was associated with VIIS-50 success.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ced\/llad105","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T08:48:15Z","timestamp":1679042895000},"page":"765-769","source":"Crossref","is-referenced-by-count":1,"title":["Characteristics and outcomes for participants with congenital ichthyosis who responded to treatment with the topical isotretinoin formulation TMB-001: results from the Phase IIb CONTROL study"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-8308","authenticated-orcid":false,"given":"Christopher G","family":"Bunick","sequence":"first","affiliation":[{"name":"Yale University School of Medicine , New Haven, CT , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce M C","family":"Teng","sequence":"additional","affiliation":[{"name":"Stanford School of Medicine, Stanford University , Palo Alto, CA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Guenthner","sequence":"additional","affiliation":[{"name":"The Dermatology Center of Indiana , Plainfield, IN , USA"},{"name":"The Indiana Clinical Trials Center , PC, Plainfield, IN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyani","family":"Marathe","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Kempers","sequence":"additional","affiliation":[{"name":"Associated Skin Care Specialists, New Brighton, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimmie","family":"Eads","sequence":"additional","affiliation":[{"name":"The Indiana Clinical Trials Center , PC, Plainfield, IN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Castelo-Soccio","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine at the University of Pennsylvania, and Children\u2019s Hospital of Philadelphia , Philadelphia, PA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan M","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Timber Pharmaceuticals , Basking Ridge, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Raiz","sequence":"additional","affiliation":[{"name":"Timber Pharmaceuticals , Basking Ridge, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-0199","authenticated-orcid":false,"given":"D\u00e9d\u00e9e F","family":"Murrell","sequence":"additional","affiliation":[{"name":"University of New South Wales School of Medicine & Health , Sydney, NSW , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"2023101015310174300_llad105-B1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2165\/11311070-000000000-00000","article-title":"Ichthyosis: clinical manifestations and practical treatment options","volume":"10","author":"Oji","year":"2009","journal-title":"Am J Clin Dermatol"},{"key":"2023101015310174300_llad105-B2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/1346-8138.13243","article-title":"Inherited ichthyosis: non-syndromic forms","volume":"43","author":"Takeichi","year":"2016","journal-title":"J Dermatol"},{"key":"2023101015310174300_llad105-B3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40257-017-0313-x","article-title":"Inherited nonsyndromic ichthyoses: an update on pathophysiology, diagnosis and treatment","volume":"19","author":"Vahlquist","year":"2018","journal-title":"Am J 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Dermatol"},{"key":"2023101015310174300_llad105-B7","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.jaad.2022.02.060","article-title":"Safety, tolerability, and efficacy of a novel topical isotretinoin formulation for the treatment of X-linked or lamellar congenital ichthyosis: results from a phase 2a proof-of-concept study","volume":"87","author":"Paller","year":"2022","journal-title":"J Am Acad Dermatol"},{"key":"2023101015310174300_llad105-B8","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.jaad.2022.07.028","article-title":"The CONTROL study: a randomized, double-blind vehicle-controlled Phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis","volume":"87","author":"Teng","year":"2022","journal-title":"J Am Acad 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