Study to Evaluate Long-Term Safety of ASN002 in Subjects With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This is a randomized open label study to evaluate the long term safety of ASN002 in subjects with moderate to severe atopic dermatitis (AD).

Detailed Description
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This is a randomized open label study where subjects with moderate to severe atopic dermatitis will roll over from the Phase 1 ASN002AD-101 (NCT03139981) and ASN002AD-201 (NCT03531957) Ph2b study and be randomized to receive ASN002 at 40mg, 60mg, or 80mg once daily for up to 24 months. This study will also characterize the pharmacokinetics of ASN002 through blood sampling from subjects who consent.

Official Title
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A Phase 2, Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of ASN002 in Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: ASN002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject with a history of moderate to severe atopic dermatitis who participated in the preceding ASN002AD-201 and ASN002AD-101 study Subject must be a candidate for prolonged open label ASN002/gusacitinib treatment according to the investigator's judgment. Subject has been using an emollient daily for at least 1 week prior to Day 1 and agrees to continue using that same emollient daily throughout the study. Men and women participating in the study must use medically acceptable birth control or total abstinence from sexual intercourse Subject is willing to participate and is capable of giving informed consent. Note: Consent must be obtained prior to any study-related procedures. Subjects must be willing to comply with all study procedures and must be available for the duration of the study. Subject has a body mass index (BMI) ≤ 38 kg/m2. Exclusion Criteria Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study. Subject has clinically infected atopic dermatitis. A serious uncontrolled condition including hypertension, history of tuberculosis, hepatitis B or C infection, immune deficiency, heart disease, heart conduction disorder, diverticulitis, diabetes, reflux disease requiring protocol pump inhibitor therapy, malabsorption syndrome, or cancer Subject has a history of skin disease or presence of skin condition that, in the opinion of the investigator, would interfere with the study assessments. Subject has a history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past. Willing to comply with discontinuation of certain treatments for AD, as directed by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASN002 40 mg<br>ASN002 40 mg | Drug: ASN002<br>* Daily dose of ASN002 for up to 110 weeks<br>|
| Experimental: ASN002 60 mg<br>ASN002 60 mg | Drug: ASN002<br>* Daily dose of ASN002 for up to 110 weeks<br>|
| Experimental: ASN002 80 mg<br>ASN002 80 mg | Drug: ASN002<br>* Daily dose of ASN002 for up to 110 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Eczema Area Severity Index (EASI) Score | The Eczema Area and Severity Index (EASI) is a composite score ranging from 0 to 72, the higher the value the worse the disease, that takes into account the degree of erythema, induration/infiltration (papules), excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the percentage of BSA involved for each body region and for the proportion of the body region to the whole body. Due to early termination of the study, all efficacy analyses were descriptive in nature | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (1) | The IGA is a global assessment of the current state of the disease. It is a 5-point (0-4) morphological assessment of overall disease severity. The IGA is selected using descriptors that best describe the overall appearance of the lesions at any given point. Signs like inflammation, redness, oozing, and crusting are evaluated. The 0 is the least severe and 4 is the most severe. Due to early termination of the study, all efficacy analyses were descriptive in nature. | 3 months | 
| Change From Baseline in 5-D Pruritus (Itch) Scale | The 5-D Pruritus Scale is a validated questionnaire used in clinical trials to assess the degree, duration, direction, disability, and distribution of the itch to rate the their symptoms over the preceding 2-week period. Each symptoms is scored on a scale of 1 to 5, with 5 being the most affected. The total score of 5-D pruritus is a sum of the 5 scores to provide a total score range from 5 (best) to 25 (worst). Due to early termination of the study, all efficacy analyses were descriptive in nature | 3 months | 
| Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS) | Intensity of itch will be measured using an NRS to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where 0 represents no itching and 10 represents worst itching imaginable Due to early termination of the study, all efficacy analyses were descriptive in nature | 3 months | 
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) | POEM developed by Charman et al. is a self-assessment of disease severity by the participant. The POEM includes 7 questions to evaluate the number of days the signs and symptoms of eczema over the last week. The answer to each question is categorized by the frequency of the sign or symptom from no days to 7 days. Each question is scored from 0 to 4 and the sum of the questions if the POEM score. The score ranges from 0 to 28 with 0 being the least frequency and 28 showing that all the signs and symptoms occur every day. Therefore, the higher the score, the more severe the eczema. Due to early termination of the study, all efficacy analyses were descriptive in nature | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eczema