Dermatitis, Atopic
Conditions
Brief summary
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.
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
Interventions
DRUGNanodox 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
Sponsors
Alchem Laboratories, Inc
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | up to 4 weeks of study drug use | comparing dermatological scores of treated lesions vs non treated lesions and treated peri-lesional areas with non-treated non-lesional areas |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus | up to 4 weeks of study drug use | (positive or negative), difference in number of growth (0 to 3+++) |
| Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area | 4 weeks of topical therapy | 1 point reduction of IGA score in Target area pre-treatment compared to post treatment (v3) |
Countries
United States
Participant flow
Recruitment details
23 were consented but 15 assigned to receive the intervention
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Topical Administration of Study Drug |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 36.5 years STANDARD_DEVIATION 16 |
| Baseline Investigator's Global Assessment IGA for Target Area Almost Clear | 1 Participants |
| Baseline Investigator's Global Assessment IGA for Target Area Clear | 5 Participants |
| Baseline Investigator's Global Assessment IGA for Target Area Mild | 9 Participants |
| Baseline Investigator's Global Assessment IGA for Target Area Moderate | 5 Participants |
| Baseline Investigator's Global Assessment IGA for Target Area Not performed | 2 Participants |
| Baseline Investigator's Global Assessment IGA for Target Area Severe | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian/ Alaskan Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized More than one Race | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or OPI | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 4 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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
Time frame: up to 4 weeks of study drug use
Population: 0 pts with treatment related adverse events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topical Administration of Study Drug | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 0 Participants |
Secondary
Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus
(positive or negative), difference in number of growth (0 to 3+++)
Time frame: up to 4 weeks of study drug use
Population: Number of patients with reduction in growth of skin flora including S.Aureus
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Topical Administration of Study Drug | Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus | Reduction of Staph species | 7 Participants |
| Topical Administration of Study Drug | Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus | Reduction of Other flora | 2 Participants |
| Topical Administration of Study Drug | Number of Participants With Reduction in Growth of Skin Flora Including S.Aureus | No growth or normal flora at V1 | 6 Participants |
Secondary
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)
Time frame: 4 weeks of topical therapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Topical Administration of Study Drug | Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area | Reduction of 1 pt | 6 Participants |
| Topical Administration of Study Drug | Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area | Reduction of </=2 pt | 7 Participants |
| Topical Administration of Study Drug | Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area | no reduction in IGA | 1 Participants |
| Topical Administration of Study Drug | Number of Participant With a Change in Investigator's Global Assessment (IGA) in Target Area | Worsening of IGA | 1 Participants |