Study to Evaluate ASN008 Topical Gel (TG)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Dermatitis, Atopic, Pruritus, Dermatitis Eczema

Intervention / Treatment
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* Drug: ASN008 TG
* Drug: Placebo TG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1, multicenter, double-blind, vehicle-controlled, randomized ascending doses trial.
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |