Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)

Phase 1

Completed

Brief Summary: A study to evaluate safety and efficacy of topical sirolimus to treat plantar keratoderma in adults with PC. Subjects may receive either placebo or treatment with at least 1 foot receiving topical sirolimus at some time. For certain phases of the study treatment assignment to the right and left foot will be randomized in a double blind fashion. Blood levels will test systemic absorption of sirolimus. Other safety and efficacy measures will be taken through the 39-week study duration. Funding Source - FDA OOPD

Recruitment & Eligibility

Inclusion Criteria

Subjects must:

Be capable of understanding the purpose and risks of the study and sign a written Informed Consent Form (ICF)
Be male or female ≥ 16 years of age at the time of the screening visit
Have a confirmed diagnosis of PC by genotyping (e.g., familial) and clinically correlated painful keratoderma.
Have roughly symmetrical calluses of similar severity on the plantar surface of both feet
Women of childbearing potential must have a negative serum pregnancy test
Subjects, whether male or female, with reproductive potential and who are sexually active must agree to use double-barrier contraception methods

Exclusion Criteria

A Subject with any of the following criteria is not eligible for inclusion in this study:

Use of other investigational drugs within 30 days of the screening visit and/or has not recovered from any side effects of prior investigational drugs or procedure in the affected area (e.g., a biopsy)
Significant condition in the dermatologic treatment area such as trauma, or nonhealing chronic wound
Pregnant or nursing (lactating) female, or a positive serum pregnancy test
Active infection either systemic or local near the site of treatment requiring chronic or prolonged use of antimicrobial agents
Known immunodeficiency including: Hepatitis A; Hepatitis B; Hepatitis C; Human Immunodeficiency Virus (HIV)

Prior and Current Treatment

Unable to be discontinued from drugs known to either be inducers or inhibitors of CYP3A4/5 enzymes
Unable to be discontinued from drugs known to be P-glycoprotein inhibitors

Arm && Interventions

Group	Intervention	Description
Split-body 1% sirolimus cream (TD201 1%)	1% sirolimus cream (TD201 1%)	This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.

Primary Outcome Measures

Name	Time	Method
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels	Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drug	The primary outcome measure for this Phase 1b safety study is evaluation of system absorption through measurement of serum sirolimus trough levels. The limit of detection of the assay was 2.0 ng/mL.

Secondary Outcome Measures

Name	Time	Method
Weekly Assessments Recorded in the PC Quality of Life Index	Weekly for 39 weeks	Patient-reported weekly assessment in the PC Quality of Life Index
Daily Assessments Recording in the PC Measurement Diary	Weekly for 39 weeks