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Congenital ichthyosis (CI) is a large, heterogeneous family of inherited skin disorders of cornification resulting from an abnormality of skin keratinization, such as scaling and thickening of the skin. Treatment options include keratolytic agents, which can abruptly lead to extensive shedding or peeling of scales. PAT-001 primarily acts as a keratolytic agent; thus, making it a potential drug candidate for the treatment of skin disorders associated with hyperkeratinization, such as CI. The current study intends to evaluate the safety and tolerability of PAT-001 in patients with CI of either the Lamellar or X-Linked subtypes.
The management of CI is a life-long endeavor, which remains largely symptomatic (i.e., emollients with or without keratolytics agents) and commonly focused on reducing scaling and/or skin lubrication with both systemic and topical treatments. A first-line therapy includes hydration and lubrication accomplished by creams and ointments containing low concentrations of salt, urea, or glycerol, which increase the water-binding capacity of the horny layer. Addition of keratolytics agents are used to decrease corneocyte cohesiveness, to promote desquamation, and to dissolve keratins and lipids (e.g., α-hydroxy acids, salicylic acid, high dose urea, propylene glycol, N-acetylcysteine, and retinoids). Systemic retinoid treatment is reserved for those patients refractory to topical agents because of long-term adverse effects and teratogenicity.
This is a two part, Phase 2, multicenter, proof-of-concept (POC) study of the safety and tolerability of PAT-001 for the treatment of Congenital ichthyosis (CI) in patients ages 12 years of age and older. Part 1 will be a double-blind, randomized, vehicle controlled, bilateral comparison of two treatments (PAT-001 [0.1% or 0.2%] vs. vehicle) for eight (8) weeks.
Part 2 will be a double-blind, active only treatment comparison of the two PAT-001 concentrations (0.1% or 0.2%) for an additional four (4) weeks. Subjects will have the option to participate in the pharmacokinetics (PK) portion of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PAT-001 0.1% | Experimental | Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). This comparison lasts from Weeks 0-8 Part 2: Patients will apply only PAT-001, 0.1% to both Treatment Areas from Weeks 8-12. |
|
| PAT-001 0.2% | Experimental | Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). This comparison lasts from Weeks 0-8 Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. |
|
| Vehicle for PAT-001 0.1% arm | Placebo Comparator | Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). The application of vehicle only lasts from Weeks 0-8. |
|
| Vehicle for PAT-001 0.2% arm | Placebo Comparator | Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). The application of vehicle only lasts from Weeks 0-8. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PAT-001, 0.1% | Drug | PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) in Part 1 of Trial (Weeks 0-8) | The number of participants with AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported. | Day 0 through Day 57 (Weeks 0-8) |
| Incidence of Local Skin Reactions (LSRs) in Participants Treated With PAT-001 0.1%, 0.2% and/or Vehicle | LSRs including burning/stinging, pain, and pruritus (itch) will be assessed in each Treatment Area using a four-point ordinal scale where 0=none, 1=mild, 2=moderate, and 3=severe (based on the investigator's evaluation of the skin reaction) at each clinic visit to allow a comparison between Treatment Groups and Test Articles. Only LSRs that require medical intervention (e.g., prescription medication) or require withholding or reduction in dosing frequency of the test articles will be documented in this LSR Table. Any LSRs that are not listed here will be recorded as AEs. | Up to Day 84 (Weeks 0-12) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving Improvement to State of Clear, Almost Clear or Mild in the Investigator's Global Assessment (IGA) Using a Five-point Scale at Day 57 (Part 1) | Overall severity of ichthyosis will be graded using a five-point scale Investigator Global Assessment (IGA) based upon a 5 point scale going from 0=clear., 1=almost clear, 2=mild, 3=moderate to 4=severe. Scoring is based upon investigator evaluation. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of PAT-001 0.1% and 0.2% at Different Timepoints | Serum concentrations for PAT-001 0.1% and PAT-001 0.2% looking at blood levels obtained at timepoints outlined | Day 1 (0,1, 2, 3, and 4 hours post Dose) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Zachary Rome, BS | Sponsor GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| TCR Medical Corporation | San Diego | California | 92123 | United States | ||
| Yale Center for Clinical Investigation |
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Each patient received both vehicle application and either PAT-001 0.1% or PAT-001 0.2% on 2 different identical matching parts of their bodies (e.g, upper thighs). Since each of the 19 patients were treated with both PAT-001 and vehicle, the number of treatment areas was 38 (19 x 2) but the number of patients was 19.
Recruitment: March 8, 2017-February 13, 2018. Recruited at 5 clinics in United States associated with US Universities by practicing dermatologists
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 PAT-001 0.1% and Vehicle | Part 1 (8 weeks): Patients will have two comparable Treatment Areas on their bodies, for example both upper arms that have same degree of disease. PAT-001, 0.1% will be applied to one of those body parts for 8 weeks, applied twice a day. The matching body part will have vehicle applied twice a day for 8 weeks Part 2 (4 weeks): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1% so that subjects cannot tell the difference between vehicle and PAT-001 based upon appearance. |
| FG001 | Group 2 PAT-001 0.2% and Vehicle | Part 1 (8 weeks): Patients will have two comparable Treatment Areas on their bodies, for example both upper arms that have same degree of disease. PAT-001, 0.2% will be applied to one of those body parts for 8 weeks, applied twice a day. The matching body part will have vehicle applied twice a day for 8 weeks. Part 2 (4 weeks): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1% so that subjects cannot tell the difference between vehicle and PAT-001 based upon appearance. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 PAT-001 0.1% and Vehicle | Part 1 (weeks 0-8): Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) in Part 1 of Trial (Weeks 0-8) | The number of participants with AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported. | Number of Participants with Adverse events | Posted | Number | participants | Day 0 through Day 57 (Weeks 0-8) |
|
84 Days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 PAT-001 0.1% | Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: PAT-001, 0.1% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| C. difficile colitis | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment | Deemed not related to study treatment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site pruritis | General disorders | MedDRA (10.0) | Non-systematic Assessment | skin reactions |
Data should be interpreted with caution due to small sample sizes
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alan Mendelsohn, MD | Timber Pharmaceuticals | 2673004249 | amendelsohn@timberpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 6, 2017 | Jun 28, 2021 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D016112 | Ichthyosis Vulgaris |
| ID | Term |
|---|---|
| D007057 | Ichthyosis |
| D012868 | Skin Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| PAT-001, 0.2% | Drug | PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. |
|
|
| Vehicle for PAT-001 0.1% | Drug | Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1%. |
|
|
| Vehicle for PAT-001 0.2% | Drug | Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.2%. |
|
|
| Up to Day 57 |
| Number of Participants Achieving an Improvement of at Least 1 Point Score in the Individual Clinical Signs/Symptoms of Erythema, Scaling, Fissuring and Papulation/Lichenification Using a Five-point Scale | Overall severity of erythema (redness), scaling , fissuring (cracks in skin), and papulation/lichenification (skin thickening, increased pigmentation and/or exaggerated skin lines, formation of papules) will be graded using a five-point scale from 0=clear, 1=almost clear, 2=mild, 3=moderate to 4=severe. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. This scoring is based upon investigator discretion. | Up to Day 57 (Weeks 0-8) |
| New Haven |
| Connecticut |
| 06519 |
| United States |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Paddington Testing Co., Inc | Philadelphia | Pennsylvania | 19103 | United States |
| Texas Dermatology and Laser Specialists | San Antonio | Texas | 78218 | United States |
| Withdrawal by Subject |
|
| BG001 | Group 2 PAT-001 0.2% and Vehicle | Part 1 (weeks 0-8): Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: (weeks 8-12) Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Median | Inter-Quartile Range | kg/m^2 |
|
| Group 2 PAT-001 0.2% |
Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: PAT-001, 0.2% will be applied to one of the 2 areas twice a day for 8 weeks Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. |
| OG002 | Group 1 Vehicle | Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: Vehicle will be applied to one of the 2 areas twice a day for 8 weeks Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. |
| OG003 | Group 2 Vehicle | Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: Vehicle will be applied to one of the 2 areas twice a day for 8 weeks Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. |
|
|
| Primary | Incidence of Local Skin Reactions (LSRs) in Participants Treated With PAT-001 0.1%, 0.2% and/or Vehicle | LSRs including burning/stinging, pain, and pruritus (itch) will be assessed in each Treatment Area using a four-point ordinal scale where 0=none, 1=mild, 2=moderate, and 3=severe (based on the investigator's evaluation of the skin reaction) at each clinic visit to allow a comparison between Treatment Groups and Test Articles. Only LSRs that require medical intervention (e.g., prescription medication) or require withholding or reduction in dosing frequency of the test articles will be documented in this LSR Table. Any LSRs that are not listed here will be recorded as AEs. | Participants may have had more than one type of LSR | Posted | Number | participants | Up to Day 84 (Weeks 0-12) |
|
|
|
| Secondary | Number of Participants Achieving Improvement to State of Clear, Almost Clear or Mild in the Investigator's Global Assessment (IGA) Using a Five-point Scale at Day 57 (Part 1) | Overall severity of ichthyosis will be graded using a five-point scale Investigator Global Assessment (IGA) based upon a 5 point scale going from 0=clear., 1=almost clear, 2=mild, 3=moderate to 4=severe. Scoring is based upon investigator evaluation. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. | Posted | Count of Participants | Participants | Up to Day 57 |
|
|
|
| Secondary | Number of Participants Achieving an Improvement of at Least 1 Point Score in the Individual Clinical Signs/Symptoms of Erythema, Scaling, Fissuring and Papulation/Lichenification Using a Five-point Scale | Overall severity of erythema (redness), scaling , fissuring (cracks in skin), and papulation/lichenification (skin thickening, increased pigmentation and/or exaggerated skin lines, formation of papules) will be graded using a five-point scale from 0=clear, 1=almost clear, 2=mild, 3=moderate to 4=severe. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. This scoring is based upon investigator discretion. | IGA score improvement of at least 1 point on IGA for scaling, erythema, papulation/lichenification and fissuring at Day 57 in patients receiving continuous 0.1% and 0.2% PAT-001 | Posted | Number | participants | Up to Day 57 (Weeks 0-8) |
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| Other Pre-specified | Pharmacokinetics of PAT-001 0.1% and 0.2% at Different Timepoints | Serum concentrations for PAT-001 0.1% and PAT-001 0.2% looking at blood levels obtained at timepoints outlined | Posted | Mean | Standard Deviation | ng/mL | Day 1 (0,1, 2, 3, and 4 hours post Dose) |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 7 |
| 10 |
| EG001 | Group 2 PAT-001 0.2% | Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: PAT-001, 0.2% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. | 0 | 9 | 1 | 9 | 7 | 9 |
| EG002 | Group 1 Vehicle | Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: Vehicle, 0.0% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG003 | Group 2 Vehicle | Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: Vehicle 0.0% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. | 0 | 9 | 0 | 9 | 1 | 9 |
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| Novavirus gastroenteritis | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| mental status changes | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment |
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| C. difficile colitis | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
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| Application site dermatitis | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Application site folliculitis | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Gastroenteritis novovirus | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Tooth infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Application site pain | General disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
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| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
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| Transaminases increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
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| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Application site irritation (mild) |
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| Application site dermatitis (moderate) |
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| Application site rash (mild) |
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| Application site reaction (mild) |
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| Application site pain (moderate) |
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| Application site Pruritis (moderate) |
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| Application site Pruritis (mild) |
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| Application site Dermatitis (mild) |
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| Fissuring |
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| Papulation/lichenification |
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| Erythema |
|
| 2 Hours |
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| 3 Hours |
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| 4 Hours |
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