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

NCT ID: NCT00716014

Last Updated: 2008-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2008-08-31

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.

Conditions

Pachyonychia Congenita

Keywords

Pachyonychia Congenita; siRNA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Foot 1

An active drug injection of TD101 is injected into a callus on the bottom of one foot.

Group Type: ACTIVE_COMPARATOR

TD101

Intervention Type: DRUG

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

Foot 2

An injection of placebo (normal saline) is injected into a callus on the bottom of one foot.

Group Type: PLACEBO_COMPARATOR

Normal saline (placebo)

Intervention Type: DRUG

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

Interventions

TD101

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

Intervention Type: DRUG

Normal saline (placebo)

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pachyonychia Congenita Project

OTHER

Sponsor Role: lead

Responsible Party

PC Project

Principal Investigators

Sancy A Leachman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

PC Project

Locations

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

24013

Identifier Type: -

Identifier Source: org_study_id