Clinical trial NCT02864082: A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis
Official title: A Randomized, Bilateral Comparison, Vehicle-Controlled, Safety and Tolerability Study of Topical PAT-001 for the Treatment of Congenital Ichthyosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Ichthyosis
Keywords: X-linked, lamellar
Lead sponsor: Patagonia Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2016-08-11
Enrollment: 19
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) in Part 1 of Trial (Weeks 0-8)
timeFrame: Day 0 through Day 57 (Weeks 0-8)
measure: Incidence of Local Skin Reactions (LSRs) in Participants Treated With PAT-001 0.1%, 0.2% and/or Vehicle
timeFrame: Up to Day 84 (Weeks 0-12)
Secondary outcomes:
measure: 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)
timeFrame: Up to Day 57
measure: 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
timeFrame: Up to Day 57 (Weeks 0-8)
Other outcomes:
measure: Pharmacokinetics of PAT-001 0.1% and 0.2% at Different Timepoints
timeFrame: Day 1 (0,1, 2, 3, and 4 hours post Dose)
Locations:
city: San Diego
country: United States
facility: TCR Medical Corporation
state: California
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation
state: Connecticut
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Philadelphia
country: United States
facility: Paddington Testing Co., Inc
state: Pennsylvania
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
Study officials:
affiliation: Sponsor GmbH
name: Zachary Rome, BS
role: STUDY_DIRECTOR
References: