Clinical trial NCT03798561: Study to Evaluate ASN008 Topical Gel (TG)
Official title: A Phase 1, Randomized, Double-Blind, Vehicle-Controlled Ascending Doses Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ASN008 Topical Gel in Healthy Volunteers and Subjects With Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dermatitis, Atopic
Pruritus
Dermatitis Eczema
Lead sponsor: Asana BioSciences
Sponsor class: INDUSTRY
First posted: 2019-01-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1, multicenter, double-blind, vehicle-controlled, randomized ascending doses trial.
Primary purpose: TREATMENT

Brief summary: This is an ascending dose escalation study to test the safety, tolerability and preliminary efficacy of ASN008 TG in first-in-human subjects

Detailed description: This is a two part, randomized, blinded, vehicle-controlled study to determine a safe and tolerable dose of ASN008 TG. Part A will asses a single ascending dose of ASN008 TG in cohorts of healthy volunteers, while Part B will assess multiple ascending doses of TG, to be determined (TBD) based on Part A safety and tolerability, in patients with mild-to-moderate dermatitis. Results from Part A and B will characterize safety, tolerability and pharmacokinetics. Part B patients will be assessed for changes in pruritus based on a numerical rating scale (NRS) of pruritus at baseline and on Day 15.

Eligibility criteria: Inclusion Criteria:

Part A - Healthy Volunteers:

* Written informed consent obtained prior to any required study-related procedure
* Healthy female or male subject aged 18 to 65
* Willing to use medically effective methods of birth control
* Females of reproductive potential must have a negative serum pregnancy test at screening and negative serum or urine pregnancy test prior to first study drug application on Day 1
* Non-smoker (no nicotine products for at least 6 months prior to screening)
* BMI ≥18.5 kg/m2 and ≤32.0 kg/m2 with minimum weight of 60 kg

Part B- Subjects with AD:

* Written informed consent obtained prior to any required study-related procedure
* Confirmed diagnosis of active atopic dermatitis (AD)
* History of AD for at least 6 months prior to Day 1 with an investigator global assessment ≥3 and body surface area covered with 1-10% AD
* Pruritus score (NRS)≥ 5 at screening and NRS ≥7 on Day 1

Exclusion Criteria:

Both Part A and Part B:

* Pregnant or breast-feeding women
* Skin disease that may interfere with study assessments
* Febrile illness within 6 days prior to Day 1, history of cancer within 5 years of Day 1, major surgery within 8 weeks prior to Day1, known immunodeficiencies, positive for hepatitis B or C or HIV infection
* Significant medical/surgical history or condition or current physical/laboratory/ECG/ vitals signs abnormality that might compromise the subject
* Corrected QT duration ≥450 milliseconds or other significant ECG abnormality
* Received marketed or investigational biological agent within 12 weeks prior to Day 1 or JAK inhibitor or nonbiological product or device within 4 weeks of Day 1 or within 8 weeks of Day 1 if investigational product used or any drug/ substance that is a strong inhibitor or inducer of CYP3A4 or CYP2D6
* Suspected hypersensitivity/allergy to lidocaine
* Significant drug or alcohol abuse or mental illness in 2 years prior to Day 1

Part A Only- Healthy Volunteers:

-Used medications or skin emollients within 2 weeks prior to Day 1 unless approved by investigator and sponsor

Part B Only - Subjects with AD:

* Has infected atopic dermatitis
* Used dupilumab 12 weeks prior to Day 1
* Used doxepin, hydroxyzine or diphenhydramine, urea containing topical products within 1 week prior to Day 1
* Used systemic antibiotics or topical medicated treatment or other systemic treatments that could affect AD 2 weeks prior to Day 1
* Received any UV-B phototherapy, excimer laser treatment or psoralen-UV-A treatment within 4 weeks prior to Day 1

Primary outcomes:
measure: Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B)
timeFrame: Part A: 14 days; Part B: 22 days
Secondary outcomes:
measure: Calculate area under the plasma concentration versus time curve (Part A and B)
timeFrame: 7 days and 16 days
measure: Calculate the Pharmacokinetic Half-life (Part A and B)
timeFrame: 7 days and 16 days
measure: Calculate the Pharmacokinetic maximum concentration (Part A and B)
timeFrame: 7 days and 16 days
measure: Change from baseline in pruritus NRS in AD subjects (Part B)
timeFrame: 22 days
measure: Change from baseline in Eczema Area and Severity Score (EASI) in AD subjects (Part B)
timeFrame: 22 days
measure: Change from baseline in Investigator Global Assessment Score in AD subjects (Part B)
timeFrame: 22 Days
Other outcomes:
Locations:
city: Cortland
country: United States
facility: Certified Research Associates
state: New York
city: High Point
country: United States
facility: Dermatology Consulting Services, PLLC
state: North Carolina
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: West Bend
country: United States
facility: Spaulding Research Clinic, Inc
state: Wisconsin
city: Montréal
country: Canada
facility: Innovaderm Recherches Inc
state: Quebec
Study officials:
affiliation: Asana BioSciences
name: Niranjan Rao, PhD
role: STUDY_DIRECTOR
References:
citation: Ramachandran R, Thompson SK, Malkmus S, Mieda T, Lin JH, Gupta S, Yaksh TL. Topical Application of ASN008, a Permanently Charged Sodium Channel Blocker, Shows Robust Efficacy, a Rapid Onset, and Long Duration of Action in a Mouse Model of Pruritus. J Pharmacol Exp Ther. 2020 Sep;374(3):521-528. doi: 10.1124/jpet.120.265074. Epub 2020 Jul 2.