Study to Evaluate ASN002 in Subjects With Moderate To Severe Chronic Hand Eczema

Study Overview
=================
Brief Summary
-----------------
Randomized double-blind/placebo study to evaluate the efficacy of ASN002 in subjects with severe chronic hand eczema.

Detailed Description
-----------------
This is a placebo controlled study where subjects with severe chronic hand eczema will be randomized (1:1:1) to receive ASN002 at 40 mg, 80 mg, or placebo once daily for 16 weeks (Part A). Then, in Part B, subjects who were assigned to placebo in the first part of the study will receive the highest dose of ASN002 (80 mg) for the rest of the treatment period (up to Week 32). The subjects who were assigned ASN002 in the first part of the study will continue on the same assigned treatment dose during the second part of the study (Week 16 to Week 32). The total treatment period of 32 weeks will be followed by a 4 week follow-up period.This study will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling and three or four biopsies from subjects who consent.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of ASN002 in Subjects With Moderate To Severe Chronic Hand Eczema Refractory to Corticosteroid Therapy

Conditions
-----------------
Chronic Hand Dermatitis

Intervention / Treatment
-----------------
* Drug: ASN002
* Drug: Placebo Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent obtained prior to any study-related procedure being performed Male or female subject, aged 18 to 75 years, inclusive, at the time of consent. Subject has a history of severe CHE for at least 6 months prior to baseline Subject has hand eczema refractory to high potency or ultra-high potency topical corticosteroids Subject has moderate to severe CHE at Day 1, as defined by a hand PGA 3 or 4. Subject has been using an emollient on their hands and feet (except those containing urea or salicylic acid) every day at the same frequency for at least 1 week prior to Day 1 Subject has a body mass index (BMI) ≤ 38 kg/m2. Female subject of childbearing potential has had a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1. Willing and able to comply with clinical visits and study related procedures. Exclusion Criteria: Presence of any of the following laboratory abnormalities at the screening visit: Hemoglobin < 11 g/dL, White blood cell (WBC) < 3.0 x 103 /μL, Platelet count < 125 x 103 /μL, Neutrophils < 1.80 x 103 /μL, Lymphocytes <0.9 x 103 /μL, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN),Total bilirubin > 1.2x ULN (except for elevated indirect bilirubin secondary to Gilbert's syndrome), Creatinine > ULN A serious uncontrolled condition including hypertension, active 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. Active skin infections of the hands and/or feet Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the patient at risk, interfere with participation in the study, or interfere with the interpretation of study results Pregnant or breast-feeding women Known hypersensitivity to ASN002 or its excipients Prior treatment with SYK or JAK inhibitors for which the subject received no clinical benefit, or the subject relapsed whilst on therapy. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASN002 40 mg<br>40 mg ASN002 | Drug: ASN002<br>* Daily dose of ASN002 for 32 weeks<br>|
| Experimental: ASN002 80 mg<br>80 mg ASN002 | Drug: ASN002<br>* Daily dose of ASN002 for 32 weeks<br>|
| Placebo Comparator: Placebo oral tablet<br>Matching placebo for ASN002 doses | Drug: Placebo Oral Tablet<br>* Daily dose of Placebo Oral Tablet for 16 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) | Percent change from baseline in hand mTLSS at Week 16. The mTLSS is an assessment of the severity of each of the following: erythema, scaling, lichenification/hyperkeratosis, vesicles, edema, fissures, and pruritus/pain. Each of these are rated using a 4-point severity scale. The ratings are added to create a total mTLSS calculated as the sum of assigned individual scores with a maximum value of 21 (most severe disease) and a minimum of 0 (no disease) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hand Physician Global Assessment (PGA) | Proportion of participants with a response of Physicians Global Assessment achieving clear (0) or almost clear (1) | 16 weeks | 
| Change From Baseline in Hand Patient Global Assessment (PaGA) | Reduction of PaGA compared to baseline where marked improvement was noted with at least 75% clear | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
eczema, hand eczema, hand dermatitis