MedPath

Study to Evaluate ASN008 Topical Gel (TG)

Phase 1
Completed
Conditions
Pruritus
Dermatitis Eczema
Dermatitis, Atopic
Interventions
Registration Number
NCT03798561
Lead Sponsor
Asana BioSciences
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
82 µg/cm2 ASN008 TG or PlaceboPlacebo TGPART A: ASN008 TG 82 µg/cm2 single application in 7 days or Placebo TG (6 subjects ASN008: 2 subjects placebo) (6:2)
328 µg/cm2 ASN008 TG or PlaceboASN008 TGPart A: ASN008 TG 328 µg/cm2 single application in 7 days or Placebo (6:2)
ASN008 TG TBD Cohort 1 or PlaceboASN008 TGPart B: ASN008 TG Cohort 1 daily application for 15 days or Placebo (9 subjects ASN008: 3 subjects Placebo) (9:3)
ASN008 TG TBD Cohort 1 or PlaceboPlacebo TGPart B: ASN008 TG Cohort 1 daily application for 15 days or Placebo (9 subjects ASN008: 3 subjects Placebo) (9:3)
ASN008 TG TBD Cohort 3 or PlaceboASN008 TGPart B: Placebo TG Cohort 3 daily application for 15 days or Placebo (9:3)
ASN008 TG TBD Cohort 3 or PlaceboPlacebo TGPart B: Placebo TG Cohort 3 daily application for 15 days or Placebo (9:3)
ASN008 TG TBD Cohort 2 or PlaceboASN008 TGPart B: ASN008 TG Cohort 2 daily application for 15 days or Placebo (9:3)
328 µg/cm2 ASN008 TG or PlaceboPlacebo TGPart A: ASN008 TG 328 µg/cm2 single application in 7 days or Placebo (6:2)
164 µg/cm2 ASN008 TG or PlaceboPlacebo TGPART A: ASN008 TG 164 µg/cm2 single application in 7 days or Placebo (6:2)
492 µg/cm2 ASN008 TG or PlaceboPlacebo TGPart A: ASN008 TG 492 µg/cm2 single application in 7 days or Placebo (6:2)
82 µg/cm2 ASN008 TG or PlaceboASN008 TGPART A: ASN008 TG 82 µg/cm2 single application in 7 days or Placebo TG (6 subjects ASN008: 2 subjects placebo) (6:2)
164 µg/cm2 ASN008 TG or PlaceboASN008 TGPART A: ASN008 TG 164 µg/cm2 single application in 7 days or Placebo (6:2)
ASN008 TG TBD Cohort 2 or PlaceboPlacebo TGPart B: ASN008 TG Cohort 2 daily application for 15 days or Placebo (9:3)
492 µg/cm2 ASN008 TG or PlaceboASN008 TGPart A: ASN008 TG 492 µg/cm2 single application in 7 days or Placebo (6:2)
Primary Outcome Measures
NameTimeMethod
Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B)Part A: 14 days; Part B: 22 days

Analyze incidence of treatment-emergent adverse events (TEAE)

Secondary Outcome Measures
NameTimeMethod
Change from baseline in pruritus NRS in AD subjects (Part B)22 days

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

Calculate the Pharmacokinetic maximum concentration (Part A and B)7 days and 16 days

Maximum concentration of ASN008 achieved after dosing

Calculate area under the plasma concentration versus time curve (Part A and B)7 days and 16 days

A plot of the concentration of ASN008 in plasma over time

Calculate the Pharmacokinetic Half-life (Part A and B)7 days and 16 days

Derive maximum blood plasma concentration of Time required for ASN008 concentration to decrease by 50%

Change from baseline in Eczema Area and Severity Score (EASI) in AD subjects (Part B)22 days

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

Change from baseline in Investigator Global Assessment Score in AD subjects (Part B)22 Days

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)

Trial Locations

Locations (5)

Progressive Clinical Research

🇺🇸

San Antonio, Texas, United States

Dermatology Consulting Services, PLLC

🇺🇸

High Point, North Carolina, United States

Certified Research Associates

🇺🇸

Cortland, New York, United States

Innovaderm Recherches Inc

🇨🇦

Montréal, Quebec, Canada

Spaulding Research Clinic, Inc

🇺🇸

West Bend, Wisconsin, United States

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