Study to Evaluate ASN008 Topical Gel (TG)

• ClinicalTrials.gov Identifier: NCT03798561
• Recruitment Status: Completed
• First Posted: January 10, 2019
• Last Update Posted: May 9, 2023
• Sponsor: Asana BioSciences
• Information provided by (Responsible Party): Asana BioSciences

Tracking Information

• First Submitted Date: January 4, 2019
• First Posted Date: January 10, 2019
• Last Update Posted Date: May 9, 2023
• Actual Study Start Date: January 14, 2019
• Actual Primary Completion Date: March 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 9, 2019)

Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B) [ Time Frame: Part A: 14 days; Part B: 22 days ]

Analyze incidence of treatment-emergent adverse events (TEAE)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 9, 2019)

• Calculate area under the plasma concentration versus time curve (Part A and B) [ Time Frame: 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) [ Time Frame: 7 days and 16 days ]
  Derive maximum blood plasma concentration of Time required for ASN008 concentration to decrease by 50%
• Calculate the Pharmacokinetic maximum concentration (Part A and B) [ Time Frame: 7 days and 16 days ]
  Maximum concentration of ASN008 achieved after dosing
• Change from baseline in pruritus NRS in AD subjects (Part B) [ Time Frame: 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
• Change from baseline in Eczema Area and Severity Score (EASI) in AD subjects (Part B) [ Time Frame: 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) [ Time Frame: 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase 1, multicenter, double-blind, vehicle-controlled, randomized ascending doses trial.

Masking: Double (Participant, Investigator)
Masking Description:

Part A: Double blinded, with exception of unblinded dispensing pharmacist Part B: Double blinded

Primary Purpose: Treatment

Condition

• Dermatitis, Atopic
• Pruritus
• Dermatitis Eczema

Intervention

• Drug: ASN008 TG
  ASN008 TG
• Drug: Placebo TG
  Placebo TG

Study Arms

• 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: 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)
  Interventions:

  • Drug: ASN008 TG
  • Drug: Placebo TG

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2019): 24
• Original Estimated Enrollment (submitted: January 9, 2019): 68
• Actual Study Completion Date: March 20, 2020
• Actual Primary Completion Date: March 20, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03798561
• Other Study ID Numbers: ASN008-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Asana BioSciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Asana BioSciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Niranjan Rao, PhD; Asana BioSciences

• PRS Account: Asana BioSciences
• Verification Date: May 2020