Study to Evaluate ASN008 Topical Gel (TG)

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

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

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic; Pruritus; Dermatitis Eczema
• Intervention / Treatment: Drug: ASN008 TG; Drug: Placebo TG

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2K4L5
      • Innovaderm Recherches Inc
• United States
  • New York
    • Cortland, New York, United States, 13045
      • Certified Research Associates
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services, PLLC
  • Texas
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Research Clinic, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 82 µg/cm2 ASN008 TG or Placebo; PART A: ASN008 TG 82 µg/cm2 single application in 7 days or Placebo TG (6 subjects ASN008: 2 subjects placebo) (6:2)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: 164 µg/cm2 ASN008 TG or Placebo; PART A: ASN008 TG 164 µg/cm2 single application in 7 days or Placebo (6:2)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: 328 µg/cm2 ASN008 TG or Placebo; Part A: ASN008 TG 328 µg/cm2 single application in 7 days or Placebo (6:2)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: 492 µg/cm2 ASN008 TG or Placebo; Part A: ASN008 TG 492 µg/cm2 single application in 7 days or Placebo (6:2)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: ASN008 TG TBD Cohort 1 or Placebo; Part B: ASN008 TG Cohort 1 daily application for 15 days or Placebo (9 subjects ASN008: 3 subjects Placebo) (9:3)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: ASN008 TG TBD Cohort 2 or Placebo; Part B: ASN008 TG Cohort 2 daily application for 15 days or Placebo (9:3)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG
Experimental: ASN008 TG TBD Cohort 3 or Placebo; Part B: Placebo TG Cohort 3 daily application for 15 days or Placebo (9:3)	Drug: ASN008 TG; ASN008 TG; Drug: Placebo TG; Placebo TG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B)	Analyze incidence of treatment-emergent adverse events (TEAE)	Part A: 14 days; Part B: 22 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculate area under the plasma concentration versus time curve (Part A and B)	A plot of the concentration of ASN008 in plasma over time	7 days and 16 days
Calculate the Pharmacokinetic Half-life (Part A and B)	Derive maximum blood plasma concentration of Time required for ASN008 concentration to decrease by 50%	7 days and 16 days
Calculate the Pharmacokinetic maximum concentration (Part A and B)	Maximum concentration of ASN008 achieved after dosing	7 days and 16 days
Change from baseline in pruritus NRS in AD subjects (Part B)	Numeric Rating Scale ranging from 0 to 10; 0 indicates no itching; 10 indicates worst possible itching; Rating of pruritis based degree, duration, direction, disability, and distribution	22 days
Change from baseline in Eczema Area and Severity Score (EASI) in AD subjects (Part B)	Measurement of area and severity of atopic dermatitis based on composite score 0 to 72 encompassing degree of erythema, induration, excoriation and lichenification; each scored from 0 to 3 with 0 indicating none and 3 indicating severe	22 days
Change from baseline in Investigator Global Assessment Score in AD subjects (Part B)	5 point morphological assessment of overall disease severity scored from 0 to 4 with 0 indicating clear (no inflammation) and 4 indicating severe (marked erythema)	22 Days

Collaborators and Investigators

• Sponsor: Asana BioSciences
• Investigators: Study Director: Niranjan Rao, PhD, Asana BioSciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Actual): March 20, 2020
• Study Completion (Actual): March 20, 2020

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Manifestations; Skin Diseases, Eczematous; Dermatitis; Pruritus; Dermatitis, Atopic
• Other Study ID Numbers: ASN008-101

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