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.
Drug: Normal saline (placebo)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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|
- Determine safety/toxicity of TD101 [ Time Frame: 18 weeks, followed by 3-month wash out period ] [ Designated as safety issue: Yes ]
- Determine efficacy of TD101 [ Time Frame: 18 weeks, followed by 3-month wash out period ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||August 2008|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
Active Comparator: Foot 1
An active drug injection of TD101 is injected into a callus on the bottom of one foot.
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.
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Sancy A Leachman, MD, PhD||PC Project|