Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)

• ClinicalTrials.gov Identifier: NCT02152007
• Recruitment Status: Completed
• First Posted: June 2, 2014
• Results First Posted: October 7, 2016
• Last Update Posted: October 7, 2016
• Sponsor: TransDerm, Inc.
• Collaborator: Pachyonychia Congenita Project
• Information provided by (Responsible Party): TransDerm, Inc.

Tracking Information

• First Submitted Date: February 5, 2014
• First Posted Date: June 2, 2014
• Results First Submitted Date: July 29, 2016
• Results First Posted Date: October 7, 2016
• Last Update Posted Date: October 7, 2016
• Study Start Date: January 2014
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2016)

Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: May 28, 2014): Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels [ Time Frame: The change in sirolimus levels 2 weeks and then monthly over time for the average study duration of 25 weeks or within 2 weeks of the last dose of study drug ]

Current Secondary Outcome Measures (submitted: October 5, 2016)

• Weekly Assessments Recorded in the PC Quality of Life Index [ Time Frame: Weekly for 39 weeks ]
  Patient-reported weekly assessment in the PC Quality of Life Index
• Daily Assessments Recording in the PC Measurement Diary [ Time Frame: Weekly for 39 weeks ]

Original Secondary Outcome Measures (submitted: May 28, 2014)

• Weekly Assessments Recorded in the PC Quality of Life Index [ Time Frame: Participants will be followed for the duration of the study, an expected average of 39 weeks ]
• Daily Assessments Recording in the PC Measurement Diary [ Time Frame: Participants will be followed for the duration of the study, an expected average of 39 weeks ]

Current Other Pre-specified Outcome Measures (submitted: October 5, 2016)

• Investigator Assessment of Local Tolerability [ Time Frame: Prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeks ]
  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
• Standardized Photographs [ Time Frame: Each study visit over 39 weeks ]
  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.

Original Other Pre-specified Outcome Measures (submitted: May 28, 2014)

• 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 (none to severe) with regard to: erythema, pruritis, stinging/burning, and crusting/erosion [ Time Frame: Local tolerability will be assessed prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeks; data will be reported as a change in severity compared to baseline for each visit ]
• Standardized photographs of the callus area will be taken at each study visit and used to determine size and local tolerability [ Time Frame: Data will be reported as a change in the appearance of the calluses on the plantar surface compared with baseline and reported for each study visit over 39 weeks ]
  An expert in the disease who is blinded to the study treatment will read the photographs. 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.

Descriptive Information

• Brief Title: Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)
• Official Title: Phase 1b Clinical Trial Using Topical Sirolimus for the Treatment of Pachyonychia Congenita
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pachyonychia Congenita

Intervention

Drug: 1% sirolimus cream (TD201 1%)

1% sirolimus cream (TD201 1%)

Study Arms

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.

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 28, 2014): 15
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2015
• Actual Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02152007
• Other Study ID Numbers: TD201 - CS01; FD-R-05116 ( Other Grant/Funding Number: Orphan Products Development (OPD) )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: TransDerm, Inc.
• Study Sponsor: TransDerm, Inc.
• Collaborators: Pachyonychia Congenita Project

Investigators

• Study Chair: Roger L Kaspar, PhD; TransDerm, Inc.

• PRS Account: TransDerm, Inc.
• Verification Date: October 2016