Efficacy, Safety, and Tolerability of Abrocitinib in Subjects With Moderate to Severe Chronic Hand Eczema Refractory to Corticosteroid Therapy

This randomized, double-blind, placebo-controlled, multicenter, phase 2 study aims to evaluate the efficacy of abrocitinib in 84 adult subjects with moderate to severe chronic hand eczema, and its effects on skin biomarkers using a noninvasive method of tape stripping.

• Abrocitinib 200 mg (Drug), also known as CIBINQO: Abrocitinib will be available in 100 mg strength tablet
• Abrocitinib 100 mg (Drug), also known as CIBINQO: Abrocitinib will be available in 100 mg strength tablet
• Placebo (Drug), also known as Inert tablet: Placebo tablet

Primary outcomes

• Change from baseline in hand modified Total Lesion Symptom Score (mTLSS) [Week 16]: The mTLSS is an assessment of the severity of each of the following: erythema, scaling, lichenification/hyperkeratosis, vesicles, oedema, fissures, and pruritus/pain. Each of these are rated using a 4-point severity scale.These ratings are then 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).

Secondary outcomes

• Change from baseline in hand modified Total Lesion Symptom Score (mTLSS) [Weeks 2, 4 and 12]: The mTLSS is an assessment of the severity of each of the following: erythema, scaling, lichenification/hyperkeratosis, vesicles, oedema, fissures, and pruritus/pain. Each of these are rated using a 4-point severity scale.These ratings are then 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).
• Reduction from baseline in hand Physician's Global Assessment (PGA) [Weeks 2, 4, 12 and 16]: The PGA is a global assessment of the current state of the disease and will be completed specific to the hands. It is a 5-point scale of overall disease severity by rating the particular signs and symptoms of chronic hand eczema (erythema, scaling, hyperkeratosis/lichenification, vesiculation, oedema, fissures and pruritus/pain).
• Change from baseline in Hand Eczema Severity Index (HECSI) [Weeks 2, 4, 12 and 16]: The HECSI scoring system incorporates both the extent and the intensity of the disease. The total sum called the HECSI score will be calculated, varying from 0 to a maximum severity score of 360 points.
• Change from baseline in Extent of Disease affected with moderate to severe chronic hand eczema (CHE) [Weeks 2, 4, 12 and 16]: The Extent of Disease will be estimated by the physician as the percentage of hand area (palmar and dorsal) affected by eczema, both hands (both surface) cumulating 100%.
• Patient Global Assessment (PaGA) measurements [Weeks 2, 4, 12 and 16]: Using the PaGA chart, subjects will be asked by the investigator to grade their overall change from baseline in their CHE by selecting the description which best matches their perception of treatment effect.
• Change from baseline in hand Dermatology Life Quality Index (DLQI) [Weeks 2, 4, 12 and 16]: The DLQI is a simple 10-question validated questionnaire that has been used in more than 40 different skin conditions.
• Change from baseline in Quality of Life in Hand Eczema Questionnaire (QOLHEQ) [Weeks 2, 4, 12 and 16]: The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. The QOLHEQ total-score ranges from 0-127 points.
• Change from baseline in pain Numerical Rating Scale (NRS) [Weeks 2, 4, 12 and 16]: The intensity of pain related to CHE will be recorded using a NRS. Pain intensity will be evaluated by asking subjects to assign a numerical score representing of the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no symptoms and 10 indicating the worst imaginable symptoms.
• Change from baseline in itch Numerical Rating Scale (NRS) [Weeks 2, 4, 12 and 16]: The intensity of pruritus associated with CHE will be recorded using an NRS. This will be evaluated by asking subjects to assign a numerical score between 0 and 10 corresponding to their worst itching over the past 24 hours, with 0 indicating no itch and 10 indicating worst imaginable itch.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Adult subject, 18 years of age or older, at the time of consent.
2. Subject has a history of moderate to severe CHE for at least 6 months prior to Day 1.
3. Subject has refractory hand eczema
4. Subject has moderate to severe CHE at screening and Day 1, as defined by a hand PGA of 3 or 4.
5. Contraceptive use by women of childbearing potential or their male partners during the study and until ≥ 4 weeks after the last study product administration
6. Female subject of childbearing potential has had a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1.
7. Subject is willing to participate and is capable of giving informed consent.
8. Subjects must be willing to comply with all study procedures and must be available for the duration of the study.

Exclusion Criteria:

1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
2. Subject has known or suspected allergic contact dermatitis of the hands and is unable to avoid exposure to the causative allergen or subjects with suspected or expected changes in irritant or allergen exposures from screening through the end of the study.
3. Subject has active skin infections of the hands.
4. Subject has a history or has current active psoriasis.
5. Subject has a history of eczema herpeticum within 12 months prior to screening, and/or a history of 2 or more episodes of eczema herpeticum in the past.
6. Subject has a history of skin disease or presence of skin condition.
7. Subject has a history of cancer prior to Day 1.
8. Subject has any clinically significant medical condition (including psychiatric condition) or physical/laboratory/vital signs abnormality.
9. Subject has a current or past medical history of conditions associated with thrombocytopenia, coagulopathy, or platelet dysfunction.
10. Subject has a current or recent clinically significant viral, bacterial, fungal, or parasitic infection.
11. Subject has a history of clinically significant heart disease.
12. Subject is ≥ 50 years old AND has a history of heart attack, other clinically significant heart problems, stroke, or blood clots (in the opinion of the investigator).
13. Presence of laboratory abnormalities at the screening visit.
14. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half lives (whichever is longer) prior to Day 1.
15. Subject has used any topical treatments that could have an impact on CHE within 2 weeks prior to Day 1, including, but not limited to, topical corticosteroids, topical retinoids, crisaborole, calcineurin inhibitors, ruxolitinib, tars, bleach, bleach baths, antimicrobials, medical devices.
16. Subject has a known hypersensitivity to abrocitinib or its excipients.
17. Subject has a known history of clinically significant drug or alcohol abuse within 6 months prior to Day 1.

• Robert Bissonnette, MD, Principal investigator, Innovaderm Research Inc.