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Study of TD101, a Small Interfering RNA (siRNA) Designed for Treatment of Pachyonychia Congenita

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ClinicalTrials.gov Identifier: NCT00716014
Recruitment Status : Completed
First Posted : July 16, 2008
Last Update Posted : November 19, 2008
Information provided by:
Pachyonychia Congenita Project

Brief Summary:
Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder affecting the nails, skin, oral mucosae, larynx, hair and teeth. Pathogenic mutations in keratin K6a, K6b, K16 or K17 act via a dominant negative mechanism, leading to manifestations of the disease. The most disabling PC symptom is a painful plantar blistering and keratoderma that requires use of ambulation devices in more than 50 percent of patients. Despite our understanding of the molecular basis of PC, current treatment is limited to mechanical removal of the thick calluses, non-specific topical keratolytics, and oral retinoids, none of which alleviates blistering or plantar pain satisfactorily. A public charity, PC Project, has been founded to support the development of treatments for PC (www.pachyonychia.org). In collaboration with this charity, a small company, TransDerm, Inc., has developed a small interfering RNA (siRNA) that specifically targets a mutation in one of the PC keratins, K6a. As this siRNA targets a single nucleotide mutation, it will only be effective against PC subjects harboring this specific mutation. There are currently only six known patients who carry this mutation in the International Pachyonychia Congenita Research Registry, but three of these patients live in Salt Lake City (a mother and two of her children). We propose to perform a Phase Ib clinical trial to test the safety and tolerability of TD101 in PC patients carrying an N171K mutation. We will complete treatment of the adult patient prior to recruitment of the minors.

Condition or disease Intervention/treatment Phase
Pachyonychia Congenita Drug: TD101 Drug: Normal saline (placebo) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single-Center, Placebo-Controlled, Rising Dose to Tolerance and Safety Study of TD101, an siRNA Designed for Treatment of Pachyonychia Congenita
Study Start Date : January 2008
Actual Primary Completion Date : August 2008
Actual Study Completion Date : August 2008

Arm Intervention/treatment
Active Comparator: Foot 1
An active drug injection of TD101 is injected into a callus on the bottom of one foot.
Drug: TD101
TD101 is injection into a callus on the bottom of one of the patient's feet

Placebo Comparator: Foot 2
An injection of placebo (normal saline) is injected into a callus on the bottom of one foot.
Drug: Normal saline (placebo)
A normal saline solution (placebo) is injected into one of the patient's feet.

Primary Outcome Measures :
  1. Determine safety/toxicity of TD101 [ Time Frame: 18 weeks, followed by 3-month wash out period ]

Secondary Outcome Measures :
  1. Determine efficacy of TD101 [ Time Frame: 18 weeks, followed by 3-month wash out period ]

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A positive genetic identification of the N171K mutation in the keratin 6a gene from a CLIA certified laboratory;
  • Witnessed, signed informed consent approved by Institutional Review Board/Ethics Committee;
  • A signed Health Information Portability and Accountability Act (HIPAA) authorization form which permits the use and disclosure of patient's individually identifiable health information for those enrolled in the United States of America;
  • Male or female subjects of any race 10 years of age and older;
  • Complete physical examination and medical history indicating no abnormalities that will interfere with study objectives;
  • Normal or not clinically significant baseline laboratory tests, including hemogram, ANA, serum chemistry panel, urinalysis, C3a, Bb, and APTT,PT;
  • Negative pregnancy test (females only).

Exclusion Criteria:

  • Females of childbearing potential not using a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices) during the study;
  • Diabetes mellitus requiring treatment other than diet and exercise;
  • Treatment of any type for cancer within the last six months;
  • History of any significant internal disease;
  • Subjects who are known to be allergic to any of the test product(s) or any components in the test product(s) or history of hypersensitivity or allergic reactions to any of the study preparations;
  • History of street drug or alcohol abuse;
  • Any patient not able to meet the study attendance requirements;
  • Subjects who have participated in any other trial of an investigational drug or device within 60 days prior to enrollment or participation in a research study concurrent with this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00716014

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United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Pachyonychia Congenita Project
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Principal Investigator: Sancy A Leachman, MD, PhD PC Project
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Responsible Party: Sancy Leachman/Principal Investigator, PC Project
ClinicalTrials.gov Identifier: NCT00716014    
Other Study ID Numbers: 24013
First Posted: July 16, 2008    Key Record Dates
Last Update Posted: November 19, 2008
Last Verified: November 2008
Keywords provided by Pachyonychia Congenita Project:
Pachyonychia Congenita
Additional relevant MeSH terms:
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Pachyonychia Congenita
Nails, Malformed
Pathological Conditions, Anatomical
Ectodermal Dysplasia
Abnormalities, Multiple
Congenital Abnormalities
Skin Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Nail Diseases
Skin Diseases