Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)

Study Overview
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Brief Summary
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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

Official Title
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Phase 1b Clinical Trial Using Topical Sirolimus for the Treatment of Pachyonychia Congenita

Conditions
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Pachyonychia Congenita

Intervention / Treatment
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* Drug: 1% sirolimus cream (TD201 1%)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Split-body 1% sirolimus cream (TD201 1%)<br>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. | Drug: 1% sirolimus cream (TD201 1%)<br>* 1% sirolimus cream (TD201 1%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | 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. | Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Assessments Recorded in the PC Quality of Life Index | Patient-reported weekly assessment in the PC Quality of Life Index | Weekly for 39 weeks | 
| Daily Assessments Recording in the PC Measurement Diary |  | Weekly for 39 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pachyonychia congenita