{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:42:52Z","timestamp":1773769372802,"version":"3.50.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"name":"Zehra Gundogan"},{"name":"Timber Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>This analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants \u2265 9\u00a0years with genetically confirmed XLRI or ARCI-LI and \u2265 2 (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%\/vehicle, twice daily for 12 weeks. The proportion of participants with \u2265 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and \u2265 2-grade reduction in Investigator\u2019s Global Assessment (IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4\u2005years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of \u2265 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Regardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and \u2265 2-grade IGA improvement vs. vehicle.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ced\/llad033","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T07:51:28Z","timestamp":1676533888000},"page":"623-630","source":"Crossref","is-referenced-by-count":7,"title":["Phase IIb randomized CONTROL study demonstrates a novel topical isotretinoin formulation, TMB-001, is safe and effective in participants with either recessive X-linked or autosomal recessive lamellar congenital ichthyosis"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-0199","authenticated-orcid":false,"given":"Dedee F","family":"Murrell","sequence":"first","affiliation":[{"name":"University of New South Wales, School of Medicine , Sydney, NSW , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce M C","family":"Teng","sequence":"additional","affiliation":[{"name":"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":"University of Pennsylvania, Perelman School of Medicine 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\/0000-0002-4011-8308","authenticated-orcid":false,"given":"Christopher G","family":"Bunick","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine , New Haven, CT , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"2023100918451018400_llad033-B1","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 Clin Dermatol"},{"key":"2023100918451018400_llad033-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 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