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Completed

NCT Number: NCT00716014

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

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.

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Key information

Conditions

Pachyonychia Congenita Abnormalities, Multiple Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Ectodermal Dysplasia Genetic Diseases, Inborn Nail Diseases Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases

Age range

10 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

TD101

Drug

TD101 is injection into a callus on the bottom of one of the patient's feet

Normal saline (placebo)

Drug

A normal saline solution (placebo) is injected into one of the patient's feet.

Primary outcomes

  1. Determine safety/toxicity of TD101

    Time frame: 18 weeks, followed by 3-month wash out period

Secondary outcomes

  1. Determine efficacy of TD101

    Time frame: 18 weeks, followed by 3-month wash out period

Sponsors and collaborators

Lead sponsor

Pachyonychia Congenita Project

Other

Registry information

Official study title

A Single-Center, Placebo-Controlled, Rising Dose to Tolerance and Safety Study of TD101, an siRNA Designed for Treatment of Pachyonychia Congenita

Important dates

Study start
2008
Primary completion
2008
Study completion
2008
First posted
Jul 16, 2008
Registry last updated
Nov 19, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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