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:10.1007/s13555-023-00923-1

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

Dermatol Ther (Heidelb). 2023 Jun;13(6):1255-1264. doi: 10.1007/s13555-023-00923-1. Epub 2023 May 11.

Authors

Kalyani Marathe¹, Joyce M C Teng^{2

3}, Scott Guenthner^{4

5}, Christopher G Bunick⁶, Steven Kempers⁷, Kimmie Eads⁵, Leslie Castelo-Soccio⁸, Alan M Mendelsohn⁹, Jessica Raiz⁹, Dédée F Murrell¹⁰

Affiliations

¹ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
² School of Medicine, Stanford University, Palo Alto, CA, USA. Jteng3@stanford.edu.
³ Department of Dermatology, Stanford University, 450 Serra Mall, Stanford, CA, 94305, USA. Jteng3@stanford.edu.
⁴ The Dermatology Center of Indiana, Plainfield, IN, USA.
⁵ The Indiana Clinical Trials Center, PC, Plainfield, IN, USA.
⁶ Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
⁷ Associated Skin Care Specialists, New Brighton, MN, USA.
⁸ Perelman School of Medicine and Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
⁹ Timber Pharmaceuticals, Basking Ridge, NJ, USA.
¹⁰ School of Medicine, University of New South Wales, Sydney, Australia.

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.

Keywords: Autosomal recessive lamellar; Congenital ichthyosis; Isotretinoin; TMB-001; X-linked recessive ichthyosis.

Associated data

ClinicalTrials.gov/NCT04154293

Grants and funding

UL1 TR001863/TR/NCATS NIH HHS/United States