Dermatology and Therapy (May 2023)

Topical Isotretinoin (TMB-001) Treatment for 12 Weeks Did Not Result in Clinically Relevant Laboratory Abnormalities in Participants with Congenital Ichthyosis in the Phase 2b CONTROL Study

  • Kalyani Marathe,
  • Joyce M. C. Teng,
  • Scott Guenthner,
  • Christopher G. Bunick,
  • Steven Kempers,
  • Kimmie Eads,
  • Leslie Castelo-Soccio,
  • Alan M. Mendelsohn,
  • Jessica Raiz,
  • Dédée F. Murrell

DOI
https://doi.org/10.1007/s13555-023-00923-1
Journal volume & issue
Vol. 13, no. 6
pp. 1255 – 1264

Abstract

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Abstract Introduction Treatment with oral retinoids can be effective in patients with congenital ichthyosis (CI) but may be associated with clinically significant laboratory changes. In this Phase 2b CONTROL study analysis, we characterize the effects of TMB-001, a novel topical isotretinoin formulation, on laboratory values in participants with X-linked recessive (XLRI) and autosomal recessive lamellar (ARCI-LI) ichthyosis at 12 weeks. Methods A randomized, double-blind, vehicle-controlled, Phase 2b study was conducted with participants ≥ 9 years of age with confirmed XLRI and ARCI-LI. Participants were randomized 1:1:1 and stratified by CI subtype to receive TMB-001 0.05%:TMB-001 0.1%:vehicle twice daily for 12 weeks. Laboratory analyses were performed at screening and Week 12. Results Among 33 enrolled participants (TMB-001 0.05% n = 11, TMB-001 0.1% n = 10, and vehicle n = 12), 52% had ARCI-LI and 48% had XLRI. At 12 weeks, there were single reports of anemia, neutropenia, leukopenia, lymphocytosis, and leukocytosis after vehicle treatment; neutropenia was reported in one participant receiving TMB-001 0.1%. There were single reports of abnormal biochemistry values—liver enzymes, creatinine, urea nitrogen, hyperkalemia, and hyperproteinemia—across treatment cohorts. Non-fasting hyperglycemia was observed in three participants receiving TMB-001 0.1% and one participant receiving vehicle. Urinalysis abnormalities reported in > 1 participant included urobilinogen (TMB-001 0.1% n = 2, vehicle n = 2), protein (TMB-001 0.1% n = 3, vehicle n = 2), and leukocyte esterase (TMB-001 0.1% n = 2). Laboratory parameter changes were asymptomatic and did not require study discontinuation or drug withdrawal. Conclusion There were no clinically significant laboratory changes in participants receiving TMB-001 isotretinoin ointment through 12 weeks of treatment, which differs from reported results for systemic isotretinoin. Trial Registration: NCT04154293.

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