Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)

This study has been completed.
Sponsor:
Collaborator:
Pachyonychia Congenita Project
Information provided by (Responsible Party):
TransDerm, Inc.
ClinicalTrials.gov Identifier:
NCT02152007
First received: February 5, 2014
Last updated: February 3, 2016
Last verified: February 2016
  Purpose
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

Condition Intervention Phase
Pachyonychia Congenita
Drug: 1% sirolimus cream (TD201 1%)
Drug: placebo cream (vehicle control)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1b Clinical Trial Using Topical Sirolimus for the Treatment of Pachyonychia Congenita

Resource links provided by NLM:


Further study details as provided by TransDerm, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 15
Study Start Date: January 2014
Study Completion Date: November 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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%)
Placebo Comparator: Placebo cream (vehicle control)
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: placebo cream (vehicle control)
placebo cream (vehicle control)

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02152007

Locations
United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
TransDerm, Inc.
Pachyonychia Congenita Project
Investigators
Study Chair: Roger L Kaspar, PhD TransDerm, Inc.
  More Information

Responsible Party: TransDerm, Inc.
ClinicalTrials.gov Identifier: NCT02152007     History of Changes
Obsolete Identifiers: NCT02057614
Other Study ID Numbers: TD201 - CS01  FD-R-05116 
Study First Received: February 5, 2014
Last Updated: February 3, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by TransDerm, Inc.:
pachyonychia congenita

Additional relevant MeSH terms:
Pachyonychia Congenita
Congenital Abnormalities
Ectodermal Dysplasia
Genetic Diseases, Inborn
Nail Diseases
Skin Abnormalities
Skin Diseases
Skin Diseases, Genetic
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2016