Pachyonychia Congenita
Conditions
Keywords
pachyonychia congenita
Brief summary
A study to evaluate safety and efficacy of topical sirolimus to treat plantar keratoderma in adults with PC. Subjects may receive either placebo or treatment with at least 1 foot receiving topical sirolimus at some time. For certain phases of the study treatment assignment to the right and left foot will be randomized in a double blind fashion. Blood levels will test systemic absorption of sirolimus. Other safety and efficacy measures will be taken through the 39-week study duration. Funding Source - FDA OOPD
Interventions
DRUG1% sirolimus cream (TD201 1%)
1% sirolimus cream (TD201 1%)
Sponsors
Pachyonychia Congenita Project
TransDerm, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must: * Be capable of understanding the purpose and risks of the study and sign a written Informed Consent Form (ICF) * Be male or female ≥ 16 years of age at the time of the screening visit * Have a confirmed diagnosis of PC by genotyping (e.g., familial) and clinically correlated painful keratoderma. * Have roughly symmetrical calluses of similar severity on the plantar surface of both feet * Women of childbearing potential must have a negative serum pregnancy test * Subjects, whether male or female, with reproductive potential and who are sexually active must agree to use double-barrier contraception methods
Exclusion criteria
A Subject with any of the following criteria is not eligible for inclusion in this study: * Use of other investigational drugs within 30 days of the screening visit and/or has not recovered from any side effects of prior investigational drugs or procedure in the affected area (e.g., a biopsy) * Significant condition in the dermatologic treatment area such as trauma, or nonhealing chronic wound * Pregnant or nursing (lactating) female, or a positive serum pregnancy test * Active infection either systemic or local near the site of treatment requiring chronic or prolonged use of antimicrobial agents * Known immunodeficiency including: Hepatitis A; Hepatitis B; Hepatitis C; Human Immunodeficiency Virus (HIV) Prior and Current Treatment * Unable to be discontinued from drugs known to either be inducers or inhibitors of CYP3A4/5 enzymes * Unable to be discontinued from drugs known to be P-glycoprotein inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drug | The primary outcome measure for this Phase 1b safety study is evaluation of system absorption through measurement of serum sirolimus trough levels. The limit of detection of the assay was 2.0 ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Assessments Recorded in the PC Quality of Life Index | Weekly for 39 weeks | Patient-reported weekly assessment in the PC Quality of Life Index |
| Daily Assessments Recording in the PC Measurement Diary | Weekly for 39 weeks | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Investigator Assessment of Local Tolerability | Prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeks | Investigator assessment of local tolerability at the application sites on the plantar surfaces will be evaluated by the Investigator according to a 4-point scale (0, 1, 2, or 3; none to severe) with regard to: erythema, pruritis, stinging/burning, and crusting/erosion |
| Standardized Photographs | Each study visit over 39 weeks | An expert in the disease who is blinded to the study treatment will read the photographs of the callus area taken at each study visit. The reader will assess changes to the calluses based on criteria such as blisters, cracks, small/large size, and red or bloody spots on the callus. Change in calluses will be reported for both the right and left foot. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Split-body 1% Sirolimus Cream (TD201 1%) This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%) | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Split-body 1% Sirolimus Cream (TD201 1%) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
The primary outcome measure for this Phase 1b safety study is evaluation of system absorption through measurement of serum sirolimus trough levels. The limit of detection of the assay was 2.0 ng/mL.
Time frame: Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drug
Population: Starting at week 13, visit 4, there were only 14 participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 4, Week 13, <2 ng/mL | 14 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 1, Baseline, <2.0 ng/mL | 15 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 2, Week 3, <2 ng/mL | 15 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 3, Week 7, <2 ng/mL | 15 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 5, Week 17, <2 ng/mL | 14 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 6, Week 25, <2 ng/mL | 14 participants |
| Split-body 1% Sirolimus Cream (TD201 1%) | Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels | Visit 7, Week 37, <2 ng/mL | 14 participants |
Secondary
Daily Assessments Recording in the PC Measurement Diary
Time frame: Weekly for 39 weeks
Secondary
Weekly Assessments Recorded in the PC Quality of Life Index
Patient-reported weekly assessment in the PC Quality of Life Index
Time frame: Weekly for 39 weeks
Other Pre-specified
Investigator Assessment of Local Tolerability
Investigator assessment of local tolerability at the application sites on the plantar surfaces will be evaluated by the Investigator according to a 4-point scale (0, 1, 2, or 3; none to severe) with regard to: erythema, pruritis, stinging/burning, and crusting/erosion
Time frame: Prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Stinging/Burning (0-3) Score | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.58 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Post, Pruritus Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Post, Stinging/Burning Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Pruritus Score (0-3) | 0.2 units on a scale | Standard Deviation 0.58 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Erythema Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Post, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.41 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Pruritus Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Stinging/Burning Score (0-3) | 0.3 units on a scale | Standard Deviation 0.61 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Stinging/Burning Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Post, Erythema Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.41 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Post, Pruritus Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Post, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Post, Stinging/Burning Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Pruritus Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Crusting/Erosion Score (0-3) | 0.4 units on a scale | Standard Deviation 0.65 |
| Split-body 1% Sirolimus Cream (TD201 1%) | Investigator Assessment of Local Tolerability | Visit 4 Post, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Crusting/Erosion Score (0-3) | 0.3 units on a scale | Standard Deviation 0.61 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Post, Crusting/Erosion Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Crusting/Erosion Score (0-3) | 0.2 units on a scale | Standard Deviation 0.38 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Post, Stinging/Burning Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.58 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Pruritus Score (0-3) | 0.2 units on a scale | Standard Deviation 0.58 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 7 Pre, Stinging/Burning Score (0-3) | 0.3 units on a scale | Standard Deviation 0.61 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.41 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Pruritus Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Post, Erythema Score (0-3) | 0.2 units on a scale | Standard Deviation 0.41 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Post, Pruritus Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Post, Stinging/Burning Score (0-3) | 0.1 units on a scale | Standard Deviation 0.26 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Erythema Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Pruritus Score (0-3) | 0.1 units on a scale | Standard Deviation 0.28 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Pre, Stinging/Burning Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Post, Erythema Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Post, Pruritus Score (0-3) | 0 units on a scale | Standard Deviation 0 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 4 Post, Crusting/Erosion Score (0-3) | 0.2 units on a scale | Standard Deviation 0.38 |
| Placebo Cream (Vehicle Control) | Investigator Assessment of Local Tolerability | Visit 1 Pre, Stinging/Burning (0-3) Score | 0.1 units on a scale | Standard Deviation 0.26 |
Other Pre-specified
Standardized Photographs
An expert in the disease who is blinded to the study treatment will read the photographs of the callus area taken at each study visit. The reader will assess changes to the calluses based on criteria such as blisters, cracks, small/large size, and red or bloody spots on the callus. Change in calluses will be reported for both the right and left foot.
Time frame: Each study visit over 39 weeks