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

Primary Purpose

Pachyonychia Congenita

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

TD101

Normal saline (placebo)

About this trial

This is an interventional treatment trial for Pachyonychia Congenita focused on measuring Pachyonychia Congenita, siRNA

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Huntsman Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Foot 1

Foot 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

Determine safety/toxicity of TD101

Secondary Outcome Measures

Determine efficacy of TD101

Full Information

NCT ID

NCT00716014

First Posted

July 15, 2008

Last Updated

November 18, 2008

Sponsor

Pachyonychia Congenita Project

1. Study Identification

Unique Protocol Identification Number

NCT00716014

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

November 2008

Overall Recruitment Status

Completed

Study Start Date

January 2008 (undefined)

Primary Completion Date

August 2008 (Actual)

Study Completion Date

August 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Pachyonychia Congenita Project

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pachyonychia Congenita

Keywords

Pachyonychia Congenita, siRNA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Foot 1

Arm Type

Active Comparator

Arm Description

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

Arm Title

Foot 2

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

TD101

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Normal saline (placebo)

Intervention Description

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

Primary Outcome Measure Information:

Title

Determine safety/toxicity of TD101

Time Frame

18 weeks, followed by 3-month wash out period

Secondary Outcome Measure Information:

Title

Determine efficacy of TD101

Time Frame

18 weeks, followed by 3-month wash out period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sancy A Leachman, MD, PhD

Organizational Affiliation

PC Project

Official's Role

Principal Investigator

Facility Information:

Facility Name

Huntsman Cancer Institute

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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