A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis

A Randomized, Bilateral Comparison, Vehicle-Controlled, Safety and Tolerability Study of Topical PAT-001 for the Treatment of Congenital Ichthyosis

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.

Study Overview

• Status: Completed
• Conditions: Congenital Ichthyosis
• Intervention / Treatment: Drug: PAT-001, 0.1%; Drug: PAT-001, 0.2%; Drug: Vehicle for PAT-001 0.1%; Drug: Vehicle for PAT-001 0.2%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • TCR Medical Corporation
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Investigation
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co., Inc
  • Texas
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of either sex aged 12 years or older.
• Females of childbearing potential should use appropriate contraception. Women of childbearing potential must have a negative pregnancy test at screening and baseline visits.
• Patient and legal representative(s), if applicable, has provided written informed consent.
• Patient has congenital ichthyosis of either lamellar or X-Linked subtype.
• Patient has two contralateral comparable Treatment Areas (e.g., each arm is affected and treatments areas can be applied equally).
• Patient is, except for their ichthyosis, in good general health.

Exclusion Criteria:

• Patient is pregnant or breast feeding, or is planning to become pregnant during the study.
• Patient has inflammatory skin disease unrelated to ichthyosis.
• Patient is currently using concomitant retinoid therapy, within two weeks (topical) or 12 weeks (oral) of Visit 2/Baseline.
• Patient is currently taking concomitant immunosuppressive drugs, including systemic corticosteroids, within two weeks of Visit 2/Baseline.
• Patient is currently enrolled in an investigational drug or device study.
• Patient has used an investigational drug or investigational device treatment within 30 days prior to Visit 2/Baseline.
• Patient is unable to communicate or cooperate with the investigator due to language problems, impaired cerebral function, or physical limitations.
• Patient is known to be noncompliant or is unlikely to comply with the requirements of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PAT-001 0.1%; 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.	Drug: PAT-001, 0.1%; PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.; Other Names: PAT-001
Experimental: PAT-001 0.2%; 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.	Drug: PAT-001, 0.2%; PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.; Other Names: PAT-001
Placebo Comparator: Vehicle for PAT-001 0.1% arm; 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.	Drug: Vehicle for PAT-001 0.1%; Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1%.; Other Names: Vehicle
Placebo Comparator: Vehicle for PAT-001 0.2% arm; 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.	Drug: Vehicle for PAT-001 0.2%; Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.2%.; Other Names: Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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.	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)

Other Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Patagonia Pharmaceuticals, LLC
• Investigators: Study Director: Zachary Rome, BS, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): February 13, 2018
• Study Completion (Actual): December 4, 2018

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: X-linked, lamellar
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosis; Ichthyosis, Lamellar; Ichthyosiform Erythroderma, Congenital
• Other Study ID Numbers: 205-9051-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No