Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)

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

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

Study Overview

• Status: Completed
• Conditions: Pachyonychia Congenita
• Intervention / Treatment: Drug: 1% sirolimus cream (TD201 1%)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Split-body 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.

Drug: 1% sirolimus cream (TD201 1%); 1% sirolimus cream (TD201 1%)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Assessment of Local Tolerability	Investigator assessment of local tolerability at the application sites on the plantar surfaces will be evaluated by the Investigator according to a 4-point scale (0, 1, 2, or 3; none to severe) with regard to: erythema, pruritis, stinging/burning, and crusting/erosion	Prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeks
Standardized Photographs	An expert in the disease who is blinded to the study treatment will read the photographs of the callus area taken at each study visit. The reader will assess changes to the calluses based on criteria such as blisters, cracks, small/large size, and red or bloody spots on the callus. Change in calluses will be reported for both the right and left foot.	Each study visit over 39 weeks

Collaborators and Investigators

• Sponsor: TransDerm, Inc.
• Collaborators: Pachyonychia Congenita Project
• Investigators: Study Chair: Roger L Kaspar, PhD, TransDerm, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (Estimate): June 2, 2014

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 5, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: pachyonychia congenita
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Pathological Conditions, Anatomical; Skin Diseases, Genetic; Nail Diseases; Skin Abnormalities; Abnormalities, Multiple; Ectodermal Dysplasia; Pachyonychia Congenita; Nails, Malformed; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: TD201 - CS01; FD-R-05116 (Other Grant/Funding Number: Orphan Products Development (OPD))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided