Topical NanoDox® for Atopic Dermatitis

A Phase 2, Exploratory Study to Investigate Safety and Efficacy of Doxycycline Monohydrate Hydrogel (NANODOX® HYDROGEL 1%) In Atopic Dermatitis

This study will investigate the safety and clinical efficacy of a novel doxycycline topical formulation in subjects with Atopic Dermatitis (AD). The investigators hypothesize that daily application of the study drug in AD subjects will reduce severity of the disease, by reducing skin driven inflammation and restoring skin barrier function. The investigators will also monitor the anti-microbial activity of this product on AD skin, as colonization with Staph aureus is typically associated with disease severity.

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: Nanodox 1% (doxycycline monohydrate hydrogel)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF HealthStreet
    • Gainesville, Florida, United States, 32653
      • UF Health Springhill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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):

1. Atypical vascular responses (e.g., facial pallor, white dermographism, delayed blanch response)
2. Keratosis pilaris/hyperlinear palms/ichthyosis
3. Ocular/periorbital changes
4. Other regional findings (e.g., perioral changes/periauricular lesions)

5. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical Administration of Study Drug; 2.5 grams of Nanodox 1% (doxycycline monohydrate hydrogel) will be applied topically to an indicated lesion daily for 28 days	Drug: Nanodox 1% (doxycycline monohydrate hydrogel); Subjects will be asked to apply NanoDOX® Hydrogel 1% once daily at bedtime for up to four weeks or until complete clearance whichever is sooner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	comparing dermatological scores of treated lesions vs non treated lesions and treated peri-lesional areas with non-treated non-lesional areas	up to 4 weeks of study drug use

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus	(positive or negative), difference in number of growth (0 to 3+++)	up to 4 weeks of study drug use
Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area	1 point reduction of IGA score in Target area pre-treatment compared to post treatment (v3)	4 weeks of topical therapy

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Alchem Laboratories, Inc
• Investigators: Principal Investigator: Anna De Benedetto, UF COM Department of Dermatology

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: September 1, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: IRB201601657 - A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No