Safety and Efficacy of ARQ-252 Cream in Subjects With Chronic Hand Eczema

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of ARQ-252 cream in subjects with chronic hand eczema

Detailed Description
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This is a Phase 1/2b multiple dose, parallel group, double blind, vehicle-controlled study of the safety and efficacy of ARQ-252 cream in subjects with chronic hand eczema

Official Title
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A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group, Double Blind, Dose Ranging, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream 0.3% in Subjects With Chronic Hand Eczema

Conditions
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Chronic Hand Eczema

Intervention / Treatment
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* Drug: ARQ-252 cream 0.3%
* Drug: ARQ-252 cream 0.1%
* Drug: ARQ-252 Vehicle Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants legally competent to sign and give informed consent. Males and females 18 years of age and older (inclusive) at the time of consent. Clinical diagnosis of chronic hand eczema, defined as hand eczema persistent for more than 3 months, or returned twice or more within the last 12 months. Generally stable disease for 6 weeks. Chronic hand eczema involving at least 0.3% body surface area total (i.e., approximately a third of one handprint) lesions on both hands added together Female subjects of childbearing potential (FOCBP) must have a negative serum pregnancy test at Screening and negative urine pregnancy test at Baseline. For FOCBP involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective contraceptive method for at least 4 weeks prior to Day 1. Additionally, from Day 1 until at least 4 weeks after the last investigational product administration, these subjects must agree to use at least 1 highly effective contraceptive method in addition to 1 barrier method according to the Contraception Requirements Section of the protocol. Females of non-childbearing potential must either be post-menopausal with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization. Males, if engaging in sexual intercourse with a female who is pregnant or a female of childbearing potential, must agree to use a condom every time during the study and every and every time subsequently until 4 weeks after the last dose of investigational product. Subjects in good health as judged by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry labs, hematology values, and urinalysis. Exclusion Criteria Concurrent skin diseases on the hands which, in the opinion of the Investigator, could confound the study (e.g., tinnea manuum). Subjects with any presence or history of psoriasis. History of a positive patch test with continued exposure to allergen. Subjects must have undergone diagnostic patch testing within 3 years prior to Baseline (Visit 2). Subjects who cannot discontinue systemic and/or topical therapies for the treatment of chronic hand eczema prior to Baseline and during the study Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Baseline Pregnant or lactating women or women planning to become pregnant during the study and / or within 28 days following the last dose of investigational product. Subjects with any serious medical condition or clinically significant laboratory, ECG, vital signs or physical examination abnormality that would prevent study participation or place the subject at significant risk, as judged by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: There are 2 cohorts of subjects. Cohort 1 (Phase 1) is a multiple dose cohort in which subjects with chronic hand eczema will be assigned to ARQ-252 cream 0.3% QD x 2 weeks to be applied to both hands (approximately 4% of BSA). Cohort 2 (Phase 2b) is a parallel group, double blind, vehicle-controlled cohort in which subjects with chronic hand eczema will be randomized to ARQ-252 cream 0.3% QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1% QD, vehicle cream BID or vehicle cream QD x 12 weeks to be applied to both hands (approximately 4% of BSA).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARQ-252 cream 0.3% QD (once daily)<br>Active Comparator | Drug: ARQ-252 cream 0.3%<br>* ARQ-252 cream 0.3%<br>|
| Active Comparator: ARQ-252 cream 0.3% BID (twice daily)<br>Active Comparator | Drug: ARQ-252 cream 0.3%<br>* ARQ-252 cream 0.3%<br>|
| Active Comparator: ARQ-252 cream 0.1% QD (once daily)<br>Active Comparator | Drug: ARQ-252 cream 0.1%<br>* ARQ-252 cream 0.1%<br>|
| Placebo Comparator: Vehicle cream BID (twice daily)<br>Placebo Comparator | Drug: ARQ-252 Vehicle Cream<br>* ARQ-252 Vehicle Cream<br>|
| Placebo Comparator: Vehicle cream QD (once daily)<br>Placebo Comparator | Drug: ARQ-252 Vehicle Cream<br>* ARQ-252 Vehicle Cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Safety, as measured by incidence of adverse events | The number of subjects reporting treatment-emergent adverse events | Week 3 | 
| Cohort 1: Safety, as measured by severity of adverse events | The severity of treatment-emergent adverse events | Week 3 | 
| Cohort 1: Safety, as measured by changes in hematology laboratory parameters | Number of subjects with changes in hematology laboratory parameters | Week 3 | 
| Cohort 1: Safety, as measured by changes in chemistry laboratory parameters | Number of subjects with changes in chemistry laboratory parameters | Week 3 | 
| Cohort 1: Safety, as measured by tolerability | The incidence of application site reactions as assessed by both the investigator and subject | Week 3 | 
| Cohort 1: Safety, as measured by pharmacokinetics | Plasma drug concentrations at pre-dose will be summarized using descriptive statistics | Week 3 | 
| Cohort 2: Investigator's Global Assessment (IGA) score of 'clear' or 'almost clear' at Week 12 | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4). Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 2: The rate of achievement of Investigator's Global Assessment (IGA) of 'clear' or 'almost clear' PLUS at least a 2-point improvement from Baseline | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability.This global assessment scale is an ordinal scale with five severity grades ranging from 0-Clear to 4-Severe. | Weeks 2, 4, 8 and 12 | 
| Cohort 2: The rate of achievement of at least a 2-point improvement in Investigator's Global Assessment (IGA) from Baseline | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability.This global assessment scale is an ordinal scale with five severity grades ranging from 0-Clear to 4-Severe. | Weeks 2, 4, 8 and 12 | 
| Cohort 2: Achievement of Investigator's Global Assessment (IGA) of 'clear' or 'almost clear' | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability.This global assessment scale is an ordinal scale with five severity grades ranging from 0-Clear to 4-Severe. | Weeks 2, 4, and 8 | 
| Cohort 2: Time to Investigator's Global Assessment (IGA) of 'clear' or 'almost clear' | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability.This global assessment scale is an ordinal scale with five severity grades ranging from 0-Clear to 4-Severe. | Week 12 | 
| Cohort 2: Change in Time to Investigator's Global Assessment (IGA) score compared to Baseline | The IGA is a static evaluation of qualitative overall chronic hand eczema severity. Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions that minimizes inter-observer variability.This global assessment scale is an ordinal scale with five severity grades ranging from 0-Clear to 4-Severe. | Weeks 2, 4, 8, and 12 | 
| Cohort 2: Change in Worst Itch Numeric Rating Scale (WI-NRS) pruritus score compared to Baseline | The WI-NRS has been developed as a simple, single item to assess the patient-reported severity of this symptom at its highest intensity during the previous 24-hour period. The WI-NRS will be determined by asking the subject's assessment of worst itch over the past 24 hours. The scale is from '0 to 10' (no itch to worst imaginable itch). | Weeks 2, 4, 8, and 12 | 
| Cohort 2: The rate of achievement of ≥4-point reduction from Baseline in Worst Itch Numeric Rating Scale (WI-NRS) pruritus score in subjects with Baseline WI-NRS pruritus score of at least 4 | The WI-NRS has been developed as a simple, single item to assess the patient-reported severity of this symptom at its highest intensity during the previous 24-hour period. The WI-NRS will be determined by asking the subject's assessment of worst itch over the past 24 hours. The scale is from '0 to 10' (no itch to worst imaginable itch). | Weeks 2, 4, 8, and 12 | 
| Cohort 2: Time to the first achievement of ≥4-point reduction from Baseline in Worst Itch Numeric Rating Scale (WI-NRS) pruritus score in subjects with Baseline WI-NRS pruritus score of at least 4 | The WI-NRS has been developed as a simple, single item to assess the patient-reported severity of this symptom at its highest intensity during the previous 24-hour period. The WI-NRS will be determined by asking the subject's assessment of worst itch over the past 24 hours. The scale is from '0 to 10' (no itch to worst imaginable itch). | Week 12 | 
| Cohort 2: Percent change in Hand Eczema Severity Index (HECSI) score compared to Baseline | HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). | Weeks 2, 4, 8, and 12 | 
| Cohort 2: Change in Numerical Rating Scale (NRS) for Pain score compared to Baseline | The NRS-Pain Scale is the most widely used instrument for pain screening. Subjects will select the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours, where 0 represents 'no pain at all' and 10 'the worst pain possible'. | Weeks 2, 4, 8, and 12 | 
| Cohort 2: The rate of achievement of ≥4-point reduction from Baseline in Pain Numerical Rating Scale (NRS) score in subjects with Baseline Pain NRS score of at least 4 | The NRS-Pain Scale is the most widely used instrument for pain screening. Subjects will select the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours, where 0 represents 'no pain at all' and 10 'the worst pain possible'. | Weeks 2, 4, 8, and 12 | 
| Cohort 2: Time to the first achievement of ≥4-point reduction from Baseline in Pain Numerical Rating Scale (NRS) score in subjects with Baseline Pain NRS score of at least 4 | The NRS-Pain Scale is the most widely used instrument for pain screening. Subjects will select the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours, where 0 represents 'no pain at all' and 10 'the worst pain possible'. | Week 12 | 
| Cohort 2: Change from Baseline in overall Quality of Life in Hand Eczema Questionnaire (QOLHEQ) score at each visit | The QOLHEQ is an instrument to assess disease specific Health Related Quality of Life (HRQOL) in patients suffering from hand eczema. The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. It consists out of 30 items which can be summarized according to four domains of HRQOL: Impairments because of (1) symptoms, (2) emotions, (3) limitations in functioning or (4) because of treatment and prevention. | Weeks 2, 4, 8, 12, 13 | 
| Cohort 2: Percent Body Surface Area (BSA) affected by disease and percent change from baseline in BSA affected by disease | The BSA affected by chronic hand eczema will be determined by the subject's hand method, where the subject's hand (including fingers) surface area is assumed to equal 1% of body surface area. | Weeks 2, 4, 8, 12 |