Topical NanoDox® for Atopic Dermatitis

Atopic Dermatitis (AD) is the most common inflammatory skin disease, affecting about 17% of children and 6% adults in the USA , . AD is characterized by skin barrier disruption, an aberrant adaptive immune response (i.e., Th2 polarized) to environmental allergens, susceptibility to cutaneous bacterial infections and intractable itch , . The intense pruritus and cutaneous infections contribute to the morbidity of AD and are major drivers of the reduced quality-of-life associated with this disease , . In the World Health Organization 2010 Global Burden of Disease survey, AD has ranked first among common skin diseases . So far, AD treatments have targeted inflammation with the widespread use of topical and more intermittent use of systemic corticosteroids. In summary, despite its high prevalence, effects on quality-of-life and economic burden - there are few effective treatments for AD.

Doxycycline are tetracycline antibiotics broadly used systemically to treat inflammatory-dermatologic conditions. Several studies in human and animal models have shown doxycycline have anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. Doxycycline have been reported to nonselectively inhibit members of the metalloproteinases (MMP) superfamily [reviewed in , ]. In addition to this direct inhibitory activity, doxycycline indirectly prevents tryptic kallikreins activation by MMPs . Growing body of evidence suggests that the tetracycline might also directly downregulate Protease Activator receptor (PAR)-2 expression and function, which was also found to play a role in induction of local inflammatory mediators . Importantly, the doxycycline antimicrobial activity could lead to reduced Staphylococcus infection/colonization in AD skin, a known trigger of AD flares

Inclusion criteria

• Male or female, 18 through 65 years of age, inclusive who are generally healthy except for active atopic dermatitis diagnosed by the following criteria.
• Active Atopic Dermatitis: Subjects must have within the last 3 months according to medical records, patient account or by medical exam of the investigator:

• Pruritus
• Eczema (acute, subacute, chronic)
• Chronic or relapsing history

Most subjects will have (seen in most cases, adding support to the diagnosis):

• Early age at onset
• Atopy
• Personal and/or family history
• Xerosis

Subjects may have (these clinical associations help to suggest the diagnosis of AD but are too nonspecific for defining or detecting AD for research or epidemiological studies):

• Atypical vascular responses (e.g., facial pallor, white dermographism, delayed blanch response)
• Keratosis pilaris/hyperlinear palms/ichthyosis
• Ocular/periorbital changes
• Other regional findings (e.g., perioral changes/periauricular lesions)
• Perifollicular accentuation/lichenification/prurigo lesions

• Moderate to Severe AD: clinical score based on Eczema Area and Severity Score (EASI) ≥ 10
• If receiving antihistamines, are on a stabilized dose, and expect to maintain this dose throughout the study
• All female subjects of childbearing potential must have a negative pregnancy test at screening visit and must be on an acceptable methods of contraception from the Screening Visit continuously until 30 days after stopping study drug.

Exclusion criteria

• As determined by the study doctor, a medical history that may interfere with study objectives (cancer, chronic illness)
• Known allergy to tetracycline
• Subjects with a systemic infection requiring a course of systemic antibiotics or antivirals within the last 2 weeks
• Unstable AD or any consistent requirement for systemic immune-modulant Rx (e.g. systemic steroids, phototherapy, Cyclosporine)
• History of use of biologic therapy (including intravenous immunoglobulin)
• Recent or anticipated concomitant use of systemic therapies that might alter the course of AD
• Recent or current participation in another research study
• Females who are breastfeeding, pregnant, or with plans to get pregnant during the participation in the study
• Subjects with a history of keloid formation
• History of lidocaine, epinephrine or Novocain allergy
• History of allergy to tape or other adhesive materials
• Hand eczema only (no body involvement).