Clinical trial NCT02910011
Conditions: Dermatitis, Atopic
Sponsor: University of Florida
Start date: 2017-05-18; Completion date: 2018-11-30
Enrollment: 23 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Arms: arm 1: 2.5 grams of Nanodox 1% (doxycycline monohydrate hydrogel) will be applied topically to an indicated lesion daily for 28 days
Interventions: intervention 1: Nanodox 1% (doxycycline monohydrate hydrogel)
Intervention descriptions: intervention 1: 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

Protocol documents:
Prot_SAP_001.pdf: 
IRB#201601657 
PI: Anna De Benedetto, MD 
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Version 5 November 8, 2017 
 
 
A Phase 2, Exploratory Study to Investigate Safety and Efficacy of Doxycycline 
Monohydrate Hydrogel (NANODOX®) 1% In Atopic Dermatitis 
 
 
Protocol Approval 
 
As authorized representative of the organizations involved with this study, we hereby 
give our dated signatures in scientific approval of the obligations and procedures set 
forth in this investigator initiated protocol as an instrument of proprietary information 
and instructions for the indicated research project. 
 
Authorization: 
 
 
 
Sponsor 
 
 
 
 
 
 
 
Date 
James Talton, PhD 
Alchem Laboratories, Inc 
 
 
 
Principal Investigator 
 
 
 
 
 
 
Date 
Anna De Benedetto, MD 
University of Florida College of Medicine 
Department of Dermatology 
 
Study Site: 
UF Health Department of Dermatology 
4037 NW 86th Terrace- 4th Floor 
Gainesville Florida 32606 
 
 
 
 
 
 
 
 
 
 
 
 


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IRB protocol -  
A Phase 2, Exploratory Study to Investigate Safety and Efficacy of Doxycycline 
Monohydrate Hydrogel (NANODOX®) 1% In Atopic Dermatitis 
Principal Investigator:  Anna De Benedetto, MD – Department of Dermatology, UF  
Phone Number: office (352) 294-4427; adebenedetto@ufl.edu 
Co-Investigators:  
- 
Gregory Schultz, PhD – Department of Obstetrics & Gynecology, UF 
Other research staff:   
Sanjuana Rodriquez, PA-C, Department of Dermatology, UF 
Kiran Motaparthi, MD – Assistant professor, Department of Dermatology, UF 
Jennifer Schoch, MD- Assistant Professor, Department of Dermatology, UF 
Kathryn Potter, MD- Resident in Training, Department of Dermatology, UF 
Michael Montuno, MD- Resident in Training, Department of Dermatology, UF 
Alexandra L. Owens , MD- Resident in Training, Department of Dermatology, UF 
Jennifer Nicole Harb, MD- Resident in Training, Department of Dermatology, UF 
Bahram Dideban, MD Resident in Training, Department of Family Medicine, UF 
 
Mary Bohannon, CCRA Research Coordinator mebohan@ufl.edu 
Lenise Thomas, LPN Research Nurse 
Gina Martorana, EPIC specialist, Department of Dermatology, UF 
Peter Nadeau, Biological Scientist III in Dr. De Benedetto’s lab, Department of dermatology, UF 
1. PURPOSE AND BACKGROUND 
Atopic Dermatitis (AD) is the most common inflammatory skin disease, affecting about 17% of 
children and 6% adults in the USAi, ii.  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 itchiii,iv. 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 diseasev, vi. In the World Health Organization 2010 Global Burden of 
Disease survey, AD has ranked first among common skin diseasesvii. 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 viii, ix].  In addition to this direct inhibitory activity, doxycycline 
indirectly prevents tryptic kallikreins activation by MMPsx. 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 


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mediatorsxi.  Importantly, the doxycycline antimicrobial activity could lead to reduced 
Staphylococcus infection/colonization in AD skin, a known trigger of AD flares.  
 
Alchem Laboratories Corp has recently acquired from Nanotherapeutics, Inc the first topical 
formulation of doxycycline: NanoDOX® Hydrogel, a novel small particle gel suspension of 
doxycycline 1%. The topical 1% doxycycline monohydrate hydrogel product is available for 
clinical testing through a FDA-cleared IND obtained in 2008 to treat chronic skin wound and a 
phase 2 study to evaluate safety and efficacy completed in 2011 at VA hospital in Gainesville 
("Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers", Protocol 
2008-DOX-NT/003, ClinicalTrials.gov Identifier: NCT00764361).  An amendment to the IND 
77520 has been filed with the FDA by Alchem Lab for the new IND indication for use in AD.  
 
Safety preclinical studies of NANODOX® were previously evaluated by Nanotherapeutics.  
Briefly, Franz diffusion cells were used to analyze the amount of doxycycline released out of a 
NanoDOX® Hydrogel or particle suspension across an exact area with respect to time.  These 
conditions may be used to mimic an exposed wound and the resulting drug release out of the 
NanoDOX® Hydrogel into the body. Overall, less than 1% w/w of the 15 mg total doxycycline 
available in the donor chamber in the gel (11.18µg, or 0.08%) as well as the suspension 
(29.88µg, or 0.21% w/w) diffused across the membrane into the receptor chamber. In a rat 
wound healing study, NanoDOX® Hydrogel was tested at doxycycline concentrations of 0.0% 
(placebo hydrogel), 0.3%, 1%, and 3% w/w as well as untreated control.  The results of the 
study demonstrated no significant differences between the histological scoring for all 
concentrations and the control.  All concentrations were judged to be non-irritants versus the 
control. In humans, NanoDOX® Hydrogel treatment was evaluated in a pilot, randomized, 
controlled trial of chronic, diabetic, lower-extremity foot ulcers.  All four chronic ulcers of diabetic 
patients treated daily with topical 1% NanoDOX® Hydrogel healed in the 20-week treatment 
period, whereas only one of three patients treated with vehicle healed (p=0.05). No adverse 
events were attributed to NanoDOX® Hydrogel treatment13. 
 
Aim of this protocol is to investigate the safety and clinical efficacy of 1% topical 
Doxycycline Monohydrate (NanoDOX® Hydrogel) in AD.  It is our hypothesis that daily 
application of NanoDOX® hydrogel blocking cutaneous proteases activity in AD subjects will 
reduce severity of the disease, by restoring skin barrier function and reducing skin driven 
inflammation. Importantly, we will also monitor the anti-microbial activity of this product on AD 
skin, as colonization with Staph aureus is typically associated with disease severity. This work 
will likely be the first step to developing new therapeutics targeting skin proteases activity.  
2. CHARACTERISTICS OF THE RESEARCH POPULATION 
Number of subjects We intend to have 15, non-pregnant, non-lactating women and men of any 
race and ethnicity, ages 18 to 65 yrs, who are generally healthy except for atopic dermatitis 
diagnosed by the US Consensus criteria complete this study. This may require enrolling up to 
30 subjects depending on retention rates and dropouts. Patients can have other allergic 
conditions such as asthma, allergic rhinitis, food allergies, etc. All AD subjects must have 


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moderate-severe AD as defined at screening by an Eczema Area and Severity Score (EASI) ≥ 
10. 
Gender of subjects We will be recruiting both male and female subjects  
Age of subjects We will be including subjects between the ages of 18 and 65 years. 
Racial and Ethnic Origin We will not have any restrictions based on racial or ethnic origin. We 
based our target research population racial and ethnic distribution on the data of the 2000 
United States Census for the Alachua Area.  
Vulnerable subjects We will not be targeting vulnerable subjects, however staff and students 
of UF and Shands may be enrolled as part of the general population with AD 
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 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 EASI ≥ 10 and/or IGA 1-2. 
- 
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. 
 
 
 


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Exclusion Criteria: 
- 
As determined by the study doctor, a medical history that may interfere with study 
objectives (cancer, chronic illness) 
- 
Known allergy to tetracycline  
- 
Hand eczema only (no body involvement). 
- 
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 anticipate becoming pregnant during the 
study time frame  
- 
Subjects with a history of keloid formation  
- 
History of lidocaine, epinephrine or Novocain allergy 
- 
History of allergy to tape or other adhesive materials 
3. METHODS AND PROCEDURES  
 
 
 
 
 
 
Study Design. We will perform a 6 weeks, pilot, investigator-initiated, single-center, open-label 
clinical study to determine the effect of NANODOX® 1% hydrogel in adult AD patients.  The 
study will be conducted in the UF Health Dermatology Department - Springhill.  
Subjects that voluntarily agreed to participate will be consented and enrolled in the study. 
Qualified subjects will be required to come to UF Dermatology Clinic for at least four visits, 
approximately 2 weeks apart, with an optional pre-screening (up to 28 days +/- 2 prior to V1) 
visit if washout is needed and/or to allow subjects to be enrolled in pre-established enrollment 
dates. Each visit will last approximately 30-60 minutes. 
Subjects will be asked to apply NanoDOX® Hydrogel 1% once daily at bedtime for total of four 
weeks (or until complete clearance) on the chosen target eczematous and adjoining clinically 
normal (perilesional) area (to cover an area of the size of an index card). NanoDOX® Hydrogel 
1% will be provided to the patient in single dose package containing 1.5 cc of hydrogel (equal to 
15mg Doxycycline) which is enough to cover a skin area of the size of an index card. Alchem 
will provide drug for the study at no cost. Of note, for systemic use doxycycline is used at 
concentration from 100 mg (antimicrobial) twice daily to 40 mg (anti-inflammatory) daily for 
periods ranging from 14 days to several months. We included non-lesional/perilesional skin to 
evaluate the safety (e.g. irritant or toxic effects) of the compound on atopic skin, as those 
subjects have a lower irritancy threshold as is compared to non-atopic subjectsxii.   Also, skin 
barrier impairment (e.g. increase water loss & increase pH) can be already detected in normal 


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appearing skin in AD subjects. It is our hypothesis that by normalizing the proteases activities, 
treatment with NanoDOX® Hydrogel will normalize skin barrier integrity.  
Subjects that are on any topical treatment (e.g. steroids, calcineurin antagonist) will be asked to 
discontinue the use of those medications only in the selected area for one week before starting 
the study (washout period). During the study, subjects will be allowed to stay on anti-histamine 
and any topical treatment (except for the treatment area) on a stabilized dose, and expect to 
maintain this dose throughout the study. In case of acute flare (e.g. intense itch, increase 
redness, pain or oozing) in the treatment area subjects will be allowed to use rescue medication 
(e.g. topical steroid or calcioneurin inhibitors that they used before the study) under the PI 
supervision. The need for rescue topical treatment will be monitored and recorded during the 
study and it will be used as an indication of the efficacy of the treatment. 
 
 
Screening visit (optional): 
1) Consenting and confirmation of inclusion & exclusion criteria 
2) Identification of the target area to be treated with NANODOX® and digital picture of the 
targeted lesion. The picture will not include subjects’ identifiers (e.g. facial features, tattoo, ect) 
3) possible washout period (topical only in the chosen area – treatment and biopsy sites) 
4) scheduling visit 1 
 
Visit 1 (Day 0):  
1) Consenting and confirmation of inclusion & exclusion criteria 
2) General History and Physical Exam (including review of concomitant medications) 
3) Urine Pregnancy test for woman of childbearing potential. Counseling on acceptable birth 
control measures to use throughout treatment period (28 days) and until 30 days after 
stopping study drug 
4) Questionnaire to clinically characterize AD  
5) Clinical score for atopic dermatitis  
6) Identification of the target area to be treated with NANODOX® and skin biopsy locations. 
Arms will be the preferable areas if lesions are present, otherwise trunk or lower extremity 
7) Digital pictures of the target area and area used for biopsy 
8) Non-invasive skin barrier Measurements: TransEpidermal Water Loss (TEWL). Optional: pH 
and Stratum Corneum (SC) hydration measurements may also be performed 
9) Repeated tape strippings (0, 5, 10, 15 tape-strippings with Cuderm™ tape) of non-lesional 
and lesional locations from treated area will be collected as part of the TEWL assessment 
and to assess for SC cohesion/integrity (rate of change in TEWL with repeated strippings). 


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Serial measurements of TEWL will be performed after tape stripping as previously 
describedxiii. This will also allow collecting proteins (eluded from the tape) for proteases 
activity assessment.  
10) Skin swab 
11) Optional Skin biopsy (5 mm punch) of a representative skin in the same anatomical area or 
symmetrical, avoiding the area that will be treated.  This biopsy may be performed on D28 at 
the same time as the post treatment biopsy. 
12) Venous blood draw to monitor AD biomarkers 
13) Dispense NANODOX® for two following weeks (14 +/- 2 monodose packages) 
- 
Subjects will be instructed to keep the NANODOX refrigerated at + 4C; subjects will be 
provided a cooler and ice packs keep the products refrigerated during transport.  
13) Provide instructions to complete at home diary.   
14) Provide date of Visit 2 and “morning of appointment” instructions 
 
Visit 2 (Day 14 +/-2):  
1) Review subject diary and address any questions, concerns, or missed doses 
2) Questionnaire to clinically characterize AD, review of medications and possible SE 
2) Clinical score for atopic dermatitis  
3) Digital pictures of the targeted area 
4) Non-invasive skin barrier Measurements: transepidermal water loss. Optional: pH and SC 
hydration measurements may also be performed. 
5) Repeated tape strippings (0, 5, 10, 15 tape-strippings with Cuderm™ tape)  
6) Dispense NANODOX® for two following weeks (14 +/-2 monodose packages) 
7) Suture removal at pre-treatment biopsy site, if applicable 
8) Review Diary instructions 
9) Provide date of Visit 3 and “morning of appointment” instructions 
 
In case of complete resolution of the treated area at V2, post treatment biopsy and swab and 
Venous blood draw will be performed at this visit (instead V3) and patient will only come back 
for 2 weeks post treatment. 
 
Visit 3 (Day 28 +/-2):  
1) Review subject diary and address any questions, concerns, or missed doses 
2)Questionnaire to clinically characterize AD, review of medications and possible SE 
3) Clinical score for atopic dermatitis  
4) Digital pictures of the targeted area 
5) Non-invasive skin barrier Measurements: transepidermal water loss. pH and SC hydration 
measurements may also be performed. 
6) Repeated tape strippings (0, 5, 10, 15 tape-strippings with Cuderm™ tape)  
7) Skin swab of treatment area 
8) Optional skin biopsy (5 mm punch) from treatment site and non-treatment site if not 
performed at Day 1 visit. 
9) Venous blood draw 
10) Provide date of Visit 4 and “morning of appointment” instructions 


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Visit 4 (Day 42 +/-5):  
1) Questionnaire to clinically characterize AD, review of medications and possible SE 
2) Clinical score for atopic dermatitis  
3) Take digital pictures of the targeted area 
4) Non-invasive skin barrier Measurements: transepidermal water loss. pH and SC hydration 
measurements may also be performed. 
5) Repeated tape strippings (0, 5, 10,15 tape-strippings with Cuderm™ tape)  
6) Suture removal at biopsy site(s) 
 
Study procedures & methods 
- 
Disease status assessment: 1) Investigator Global Assessment (IGA), which will 
provide information of the overall disease (four point scale: clear, mild, moderate, 
severe) and it is the score requested by FDA for clinical study and 2) Eczema Area and 
Severity Index (EASI), a well-accepted and validated scoring system for general disease 
activityxiv. It is the sum of the intensity scores (0 to 3) for four signs: erythema, induration, 
excoriation, lichenification and it is recorded for targeted treatment areas as well as four 
regions of the body (i.e., head, trunk, lower and upper extremities). Data will be reported 
as percent change in EASI score from baseline and each visit. Proportion of participants 
achieving EASI50 and EASI75 will be determined at each study timepoints. The 
presence or absence of skin irritation (e.g. macular/papular eruption), redness, atrophy 
and telangiectasia will be noted at each study visit.  
3) The pruritus intensity will be assessed using the 5-D Pruritus Scale.  The pruritus 
categorical scale is a 4-point scale commonly used in clinical studies of AD and has less 
of a “middling” effectxv The scale is rated as follows: 0: absence of pruritus; 1: mild, 
pruritus (occasional slight itching/scratching); 2: moderate pruritus (constant or 
intermittent itching/scratching that does not disturb sleep) and 3: severe pruritus 
(bothersome itching/scratching that disturbs sleep).  
- 
Digital pictures: A digital picture will be taken with a dedicated digital camera. The 
pictures will be labeled with the subject’s study ID and date. Pictures will not include 
identifying information (e.g. facial features, tattoo, etc). Pictures will be taken at a 
distance for easy identification of the anatomical area and closer to better capture 
clinical changes. Digital photographs will be used to record the location and monitor the 
size of target lesions.  Quantification of change in size will be obtained using Image J 
software.   
At conclusion of the study, two trained physicians/dermatologists will be asked to score 
clinical pictures (0-4 scale, clear, mild, moderate, severe) in a blind fashion (i.e., pictures 
will be de-identified and presented randomly/ not in chronologic order). This would allow 
to objectively confirm the clinical score taken during the study.   
- 
Skin swab: Skin swabs will be collected for microbiologic analysis to obtain a semi-
quantification of skin bacteria pool, including S. aureus spp. and to determine antibiotic 
sensitivity. Skin swabs are performed by swiping and rolling a sterile cotton-tipped 
applicator 4-5 times across the target area.  Swabs will be obtained from NanoDOX® 
Hydrogel sites pre and post treatment and may be repeated as needed to monitor 


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bacteria growth during study. The microbiology assay will be run by the Clinical 
microbiology laboratory at the University of Florida (Rocky Point Lab). 
- 
Optional Skin biopsy: One skin biopsy sample (5 mm ≈ pencil eraser size) will be 
obtained if possible within 4 cm from the treatment area or on the contralateral side. 
Second biopsy will be obtained from the treatment area post-treatment.  Biopsy will be 
performed after injecting a local anesthetic (Lidocaine +/- epinephrine) to minimize pain 
and bleeding. The biopsy will consist of removing a piece of skin with a sterile 5-mm skin 
biopsy punch. At the biopsy site one or two sutures will be placed to ensure better 
healing, minimize blood loss and to provide a more aesthetic scar formation. A pressure 
bandage will be applied to the biopsy site to minimize the risk of bleeding and infection. 
We will provide each subject with a wound care instruction sheet. 
Each biopsy will be used for analysis of proinflammatory cytokines (TSLP, IL33, TNFa, 
IL-1b, and IL-6) and epidermal barrier related protein (e.g. filaggrin, loricrin, claudin1, 
S100A7) as well as proteases activity (MMPs, elastase) that are typically upregulated in 
inflammatory skin. This will be done in collaboration with Dr. Gregory Schultz (Professor 
of Obstetrics/Gynecology & Ophthalmology at the University of Florida, co-PI in the 
study). It is our hypothesis that NanoDOX® Hydrogel by reducing the proteases activity 
in the epidermis will enhance the integrity of epidermal barrier structure.  Secondarily, 
we will evaluate changes in inflammatory (and pro-inflammatory) pathways downstream 
to proteases activity before and after treatment with NanoDOX® Hydrogel. We expect 
that normalization of molecular pattern parallels clinical improvement (and restore of skin 
barrier integrity). 
- 
Tape stripping for proteases activity measurements: the most superficial layers of 
the skin will be collected by tape stripping using D-squame (D-squame®, CuDerm, 
Dallas TX, USA – Figure 2). This is a well-established method used in clinical research 
to gently perturb the skin barrier. The first tape will be discarded to eliminate dirt and 
remnants of skin products. Each tape will be gently pressed against the skin with 
standardized pressure for 10 seconds (sec) using a standardized pressurizer (D500–D-
squame® pressure instrument, CuDerm, Dallas, TX, USA – Figure 2).  Non-lesional skin 
samples will be collected from the volar side of the forearm and lesional skin samples 
will be collected from an easily accessible area, such as arms or lower legs. 
All subjects will have 20 consecutive tapes collected from lesional skin and 20 
consecutive tapes from non-lesional skin. Once the tapes have been collected, as part of 
this study, we will test different methods to elute the skin proteins from the tapes. 
The corneocytes (cells in the most superficial layer of the skin) or their cellular contents 
that adhere to the discs must be released from the adhesive coating for subsequent 
analytical steps. So far several groups were able to use this non-invasive method to 
analyze for the presence of biomolecules, drugs and other cellular constituents. 
- 
Skin barrier measurements: Transepidermal water loss/TEWL, +/- pH and SC 
hydration measurements will be obtained on treatment area at a non-lesional site and on 
a site of inflammation. For each of the specific measurements, a probe will be gently 
applied on the skin surface for few (up to 30) seconds. We will perform all 
measurements in a climate-controlled examination room with temperatures ranging 20-
22°C and consistent humidity (preferably 40%).  The patient must be very comfortable in 


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the room in which they are being tested to ensure that perspiration due to stress or 
acclimatization does not alter the TEWL. TEWL will be measured at baseline and after 
tapestripping. SC hydration and surface pH will be assessed on non-lesional and 
lesional skin using the Corneometer® CM825 and Skin-pH-Meter® PH 905, respectively 
(Courage and Khazaka Electronic GmbH, Kohn GE – Figure 1). TEWL will be assessed 
using the AquaFlux (Biox, London UK). These measurements should provide data to 
determine if the treatment has an effect on skin barrier integrity. 
- 
Venous blood sample: (4 ml) will be obtained to evaluate biomarkers of disease 
severity. 4mLs will be collected into a redtop serum blood collection tube and allowed to 
clot at room temperature for minimum of 30 minutes. Blood will be spanned down and 
serum pipetted into Eppendorf tubes to be stored in -80°C. Tubes will be labeled with 
study subject ID, data and Visit number, not subject identifying information Tubes will be 
stored in Dr. De Benedetto’s laboratory for measurement of Th2 biomarkers (markers of 
disease severity), including serum total IgE and TARC/CCL17. 
 
4. RISK, BENEFITS and PROTECTION AGAINST RISKS 
 
Risks Associated with Digital Picture 
There are no known risks for the digital picture. The image will not include identifying features 
and will be labeled with study subject ID and date. Pictures will be taken with a dedicated 
camera, stored on a secure server and transferred into RedCap database. 
Risks Associated with Barrier Assessments 
There are no known risks for the barrier assessments. 
Risks Associated with Tape Stripping 
The risks associated with tape stripping, theoretically, include the rare possibility of an allergic 
reaction to the tape and infection.  Since the tape is removed immediately after application, the 
risk of reaction is extremely low.  We will exclude study subjects with known allergy to tapes or 
adhesive material. In previous and ongoing studies involving tape stripping, it has been noted 
that a very mild erythema may develop immediately after a series of tape strippings on one 
localized area of skin, presumably due to the mild mechanical disturbance.  The erythema is 
expected to resolve within 12 hours without sequelae.  The risk of skin infection is extremely low 
since only superficial skin layers are removed.  Subjects will be provided with wound care 
information and a department phone number to contact should they have any concerns.  
Risks of Phlebotomy 
The risks of having blood drawn include some pain when the needle goes in, and a small risk of 
bruising and/or infection at that site. Some people will get lightheaded, nauseous, or faint. 4mLs 
is approximately 1 teaspoon of blood and is not likely to cause lightheadedness, however 
subjects will be observed after blood draw to be sure they are comfortable with deambulation. 
Subjects will be encouraged to drink plenty of water prior to the blood draw. Phlebotomy will be 
performed at the antecubital fossa to minimize pain and bruising. Subjects will be seated during 


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the blood draw to minimize dizziness and any risk of falling. Pressure will be applied to the site 
after the draw and a band-aid will be applied to minimize the risk of bleeding and infection. 
 
 
Risks of Punch Biopsy 
The biopsies will be no larger than 5 mm in diameter (about a pencil eraser head). A 
nonabsorbable suture (1-2 stiches) will be placed in each site for hemostasis and enhanced 
wound healing. A small scar will remain at the site. The scar will be smaller than the initial 
biopsy but may also be hypo- or hyperpigmented. Sutures will be removed in 14 (+/- 2) days. 
The risks of this procedure include adverse reaction to anesthesia (lidocaine), pain, bleeding, 
infection and hypertrophic scars or keloids. Patients with a history of Novocain or lidocaine 
allergy or a history of keloid formation will not be allowed to participate in order to minimize the 
risk of adverse reactions. Biopsy will be performed after injecting a local anesthetic to minimize 
pain. A pressure bandage will be applied to the biopsy site to minimize the risk of bleeding and 
infection. Written wound care instruction will be provided to the subjects after the procedure. In 
case of increased redness, pain or oozing of the sites subjects will be instructed to call the 
dermatology department if appropriate subjects will be asked to come to clinic in the next 24-48 
hours for wound check. 
 
Risks of NANODOXY® 1% hydrogel 
Subjects may experience local irritation including redness, pain, stinging or burning sensation in 
the treatment area. Systemic doxycycline can enhance sensibility to the sun light. It is possible 
that topical application might temporarily enhance risk of sunburn in the treated site. To 
minimize risk of sunburn we will instruct the subjects to apply the topical at bedtime and rinse off 
in the morning. In case of sun exposure subjects should use appropriate sun protection (SPF 
>30 or clothing). Some patients may experience some irritation from the NANODOX® hydrogel 
especially in areas of open skin from scratching. Some patients may experience increased 
dryness from the hydrogel formulation.  All patients will be advised to moisturize in the morning 
and use gentle body wash to minimize these potential side effect.  
 
As for any antibiotic, there might be a risk of inducing antibiotic resistance. To minimize the risk 
the drug will be used only until the lesion is active/visible. Also we will be monitoring for bacteria 
growth during the study to determine possible change in bacteria contamination as well as 
antibiotic resistance. 
  
Preclinical studies have shown that over time (12-24 hours) the color of leftover products in the 
package might change from a white transparent tone to a more yellow-brown color. Change in 
color has not been associated with change in efficacy. To minimize risk of skin discoloration we 
will advise the subjects to rinse off the site in the morning.  
 
Subjects with sensitivity to doxycycline might develop an allergic drug reaction, which could vary 
from local irritation to more severe systemic reaction. Subjects with sensitivity/allergy to 


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tetracycline will not be enrolled in the study.  
 
In case of any abnormal reaction we will instruct the subjects to call the dermatology office and 
stop using NANODOX® until discussing symptoms with study team.  
 
Risks to children or pets are not known and subjects will be instructed to keep the products out 
of reach from children and pets. Because this is an investigational medication/formulation some 
side effect may not yet be known. Any adverse reaction will be accounted. 
 
Based on preliminary data, we do not anticipate any complications associated with the use of 
topical doxycycline.  
 
Common skin reactions with taking oral 
doxycycline include:  
• 
Redness  
• 
Swelling  
• 
Blistering rash  
 
Common allergic reactions with taking oral 
doxycycline include:  
• 
Hives  
• 
Shortness of breath  
• 
Swelling of the face, lip, tongue, or     
         throat  
 
Common systemic reactions with taking oral 
doxycycline include:  
• 
Headache  
• 
Dizziness  
• 
Fever  
• 
Chills  
• 
Rash  
• 
Nausea  
• 
Vomiting  
• 
Diarrhea  
• 
Thrush  
• 
Vaginitis  
If a subject experiences an unexpected reaction to the investigational product, it should be 
recorded as an AE or SAE.  
 
The study agent (NanoDOX™ Hydrogel) consists of doxycycline gel 1% w/w.  The 1% w/w 
doxycycline formulation of NanoDOX™ Hydrogel contains:  1% w/w doxycycline monohydrate in 
carboxymethylcellulose (CMC), a hydrogel.  CMC functions as the vehicle for the doxycycline 
active ingredient and assists in providing a moist wound environment.  The primary function of 
doxycycline in NanoDOX™ Hydrogel is to promote wound healing by harnessing doxycycline's 
inhibition of matrix metalloproteinase (MMPs) and TNF-a converting enzyme (TACE).  This 
property of doxycycline is hypothesized as the mechanism of action of NanoDOX™ Hydrogel for 
enhanced wound-healing. 
 
Alchem will prepare, package and label the investigative material in easy-to-open 1.5 gram 
disposable packets.  Each packet of doxycycline gel will have a two-part tear-off label.  The gel 
should be refrigerated between applications.  
 
Bench Testing  
Systemic absorption of the doxycycline component in NanoDOX® Hydrogel through the skin 
was evaluated by Nanotherapeutics.  Briefly, Franz diffusion cells were used to analyze the 
amount of doxycycline released out of a NanoDOX® Hydrogel or particle suspension across an 
exact area with respect to time.  These conditions may be used to mimic an exposed wound 
and the resulting drug release out of the NanoDOX® Hydrogel into the body. Overall, less than 
1% w/w of the 15 mg total doxycycline available in the donor chamber in the gel (11.18µg, or 
0.08%) as well as the suspension (29.88µg, or 0.21% w/w) diffused across the membrane into 
the receptor chamber. 


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Animal Testing  
In a rat wound healing study, NanoDOX® Hydrogel was tested at doxycycline concentrations of 
0.0% (placebo hydrogel), 0.3%, 1.0%, and 3.0% w/w as well as untreated control. The results of 
the study are:  
a) No significant differences between the histological scoring for all concentrations and the 
control; and,  
b) All concentrations were judged to be non-irritants versus the control.  
 
Details relating to additional in vivo and in vitro nonclinical pharmacology and nonclinical 
toxicology studies of NanoDOX® Hydrogel can be found in the Investigator’s Brochure. 
Reproductive Risks 
The effects of topical doxycycline on an unborn fetus or nursing (breast feeding) infant are 
unknown. It is possible that use of NANODOX® hydrogel may be associated with unanticipated 
risks to a pregnancy or fetus. Women of child bearing potential will be counseled to use 
acceptable birth control methods. Women will not be allowed to participate in this study if they 
are pregnant, become pregnant, or are nursing an infant. 
 
Property damage risks 
Objects in contact with NANODOX® may have discoloration (e.g. bedding, towels, clothes). 
Subjects are advised to be careful handling the opened NANODOX® packages and to rinse the 
excess of product from their skin if the observe change in color to minimize the likelihood of 
stain on towels, rugs or other clothing.  
General Risks 
When participating in any research study there is a possibility for invasion of privacy or breach 
of confidentiality.  
Adverse Event Reporting 
An adverse event (AE) is any observation whether or not considered to be product related, that 
is unfavorable and unintended and that occurs after any use of an investigational medicinal 
product. 
Any observation of abnormality will be documented on the Adverse event form.  The 
Investigator will document the date of occurrence, severity, resolution, and will assess the 
relationship of the adverse event to the study drug by assigning a causality assessment. 
Results from laboratory evaluations which are outside of the laboratory reference range will 
constitute an adverse event only if the Investigator determines that the result is clinically 
significant.  
Severity will be assessed by the following system:  
• 
Mild: easily tolerated, causing minimal discomfort  
• 
Moderate: sufficiently discomforting to interfere with every day activities  
• 
Severe: prevents normal every day activities 


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Serious Adverse Events 
FDA definition: A serious adverse event results in death, is life-threatening, requires inpatient 
hospitalization or prolongation of existing hospitalization, results in persistent or significant 
disability / incapacity, results in a congenital anomaly / birth defect. Events fitting these 
descriptions will be considered adverse events if they occur after treatment with the study drug. 
As soon as reasonably possible, subjects will contact the Investigator to report any unfavorable 
events. The Investigator will assess the case, determine the need for treatment, and consult 
with Alchem Laboratory, Inc, particularly in the occurrence of: 
 
A serious adverse event. 
 
An unusual frequency of non-serious adverse events. 
 
Death, even if this does not appear to be related to therapy with the study drug.  
The Investigator will notify the sponsor (Alchem Laboratory, Inc and CTSI) and the UF 
Institutional Review Board within approximately 3 working days if a serious adverse event 
occurs.  
Causality assessments 
 
Probable 
              All of the following apply: 
 
Reasonable association in time between the administration of the study drug and 
onset and duration of the reported event. 
 
Description of the clinical phenomenon should be consistent with, or at least 
plausible, given the known pharmacology and toxicology of the product. 
 
There should be no other equally plausible explanation(s) of the case. In particular, 
concurrent use of other products (and possible interactions) or concurrent disease 
should be taken into account in the assessment. 
Possible 
 
The causality is one (of other) possible and plausible causes for the described 
event, but the data do not meet the criteria for inclusion in Category A. 
Unknown 
 
An association with the study drug cannot be discounted, but other factors prevent 
a conclusion from being drawn. 
Unlikely 
 
Sufficient information exists to establish beyond reasonable doubt that the product 
was not likely to be the cause of the event. 
Classification of adverse events 
At the conclusion of the study, Medicinal Dictionary for Drug Regulatory Authorities (MeDDRA) 
terms will be assigned to all adverse events and will be included in the final study report.  
Stopping Criteria 
If more than 5 patients report a greater than moderate local side effect (irritation, worsening of 
rash, etc) or if the clinical dermatological score in the target lesion area as assessed by the 
clinician has worsened by more than 50% from baseline in more than 5 patients, then all 


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patients will stop medication until further review and changes made to the protocol.  If any 
unanticipated serious adverse effects are noted all subjects will be notified and changes will be 
made to future protocols and submitted for approval. 
5. DATA ANALYSIS AND DATA MONITORING 
Primary Outcomes:  
1. Assessment of safety and tolerability of NanoDOX® Hydrogel in AD subjects on lesional and 
non-lesional (clinically normal appearing) skin, including pain and dermatologic/skin toxicity 
(incidence, severity, frequency, duration and causality) in lesional skin at target site 
(NanoDOX® Hydrogel). 2. Improvements rate of IGA and EASI score in lesional skin treated 
with NanoDOX® Hydrogel before and after treatment. We will quantify clinical improvement as: 
IGA (0-4) fold improvement from baseline; percent of subjects reaching EASI50 (50% 
improvement over baseline) or EASI75 (75% improvement over baseline) at each time point 
post treatment (V2 and V4). 3. Objective Clinical improvement based on digital photography 
scoring (0-4 scale and size of active lesion), measured as fold improvement over baseline at 
each time point (V2 and V4). 
Secondary Outcomes:  
1. Improvements of itch score (0-5 scale) in lesional skin, before and after treatment at each 
time point. 2. Will evaluate Staphylococcal Aureus rate of colonization (positive or negative), 
difference in number of growth (0 to 3+++) and antibiotic sensitivity pre and post treatment.  
Doxycycline could have an effect on AD lesions just by reducing the Staphylococcal Aureus 
colonization. By integrating these findings with clinical outcomes, drug penetration and 
molecular changes we will be able to start to address this question. 3. Improvement of barrier 
function in non-lesional (normal appearing) and lesional skin pre and post treatment (V1 to V3). 
We will expect that clinical improvement parallels with improvement of barrier function, such as 
reduced TEWL, increased stratum corneum hydration and reduced pH in active treatment 
areas. On the other hand, worsening of the measurement will suggest damaging effect of the 
treatment on the skin, which could be indication of subclinical irritation induced by the treatment 
and/or vehicle. 
The purpose of this study is a proof of concept.  We are adopting a similar strategy to Phase II 
cancer trials that seek a clinically significant response.   Using exact binomial methods, we shall 
obtain point and interval estimates for the fraction of subjects who respond as (a) At least EASI 
50% by visit 2 or 4 and (b) At least EASI 75% by visit 2 or 4. We shall also tabulate the IGA 
score from baseline to visit 4.    We would consider 6 or more responses (a) in 15 subjects as 
promising.  The probability of declaring a promising result when the true response rate is 60% or 
higher is over 96% (power). 
 
Side effects and baseline characteristics will be tabulated qualitatively.  The blinded pre-vs post 
evaluation will be analyzed for IGA scores by the Wilcoxon sign-rank test.    
 
Data Storage and Confidentiality 


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All data from the clinical trial will be securely stored using the REDCap. We have already 
obtained funding to work with CTSI to build the REDCap database for the study. 
Only the minimal necessary data is being collected.  This includes: Name, contact information, 
age, sex, MRN, history of allergies, dermatologic diagnosis, history of other medical conditions, 
current medications and clinical scores.  This information will be stored in REDcap.   
Samples will be assigned unique identifiers and stored separately from the key linking the 
sample to the identifiers.  The electronic key will be stored in REDcap file, accessible only to 
study personnel.  Any paper documents containing identifiers will be kept in a binder in a locked 
cabinet accessible only to study personnel.   
 
 
Data Monitoring 
 
The study will be monitored in compliance with the relevant parts of 21 CFR and according to 
the ICH GCP Guidelines. 
 
A Monitor will visit the Study Center on a pre-arranged schedule to monitor adherence to the 
protocol and to applicable FDA regulations; and the maintenance of adequate and accurate 
clinical records.  A Case Report Form will be completed for every subject that was enrolled to 
participate in the Study.  The Case Report Form (CRF) will be reviewed in detail, for which the 
Monitor will have access to subject study records, laboratory data, and other source 
documentation.   
 
Case Report Forms will be completed as information becomes available or within five days of a 
Study Visit. 
 
Case Report Forms will be reviewed in detail by the Monitor who will make a decision as to their 
acceptability.  If errors or omissions are found in the course of a data audit, or if clarification of 
data is required, the Case Report Form(s) in question will be corrected by the Investigator or 
his/her designee.  Data Resolution or Query Forms may be generated on omissions or 
clarifications, to be completed, signed and dated, and maintained as a part of the CRF. 
 
The Principal Investigator or a Sub-investigator will sign and date the indicated places of the 
Case Report Form.  This signature will indicate that thorough inspection of the data therein has 
been made and will thereby certify the contents of the form.   
 
The procedures outlined in the protocol and case report forms will be carefully reviewed by the 
Sponsor, Investigator and staff prior to Study Initiation to ensure appropriate interpretation and 
implementation.  No deviations from the protocol shall be made except in emergency situations 
where alternative treatment is necessary for the protection, proper care and well being of 
subjects. 
 


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Amendments will be submitted to the IRB for their review and approval prior to implementation.  
When an amendment to a protocol substantially alters the study design or increases potential 
risk to the study subject, the Informed Consent form will be revised and if applicable, subject’s 
consent to continue participation will again be obtained. 
 
5. SUBJECTS IDENTIFICATION, RECRUITMENT AND CONSENT 
Method of subject identification and recruitment 
Dr. Anna De Benedetto will identify potential subjects from the CTSI consent2share cohort, UF 
dermatology clinics, the IRB-approved Dermatology Research database (IRB201600411) or 
from advertisements (UF website, fliers and newspaper advertisements) directed at the general 
population. In the case of clinical subjects, Dr. De Benedetto will provide the subject with a 
contact phone number for the study coordinator who is approved to enroll and consent subjects. 
While Dr. De Benedetto will be available for questions, consent might be obtained by other 
study personnel for subjects she sees in her clinical practice. It will be made clear to the 
potential subjects that their participation is voluntary and their care at the Department of 
Dermatology will not be affected by their decision to participate in this study. 
 
Process of consent  
Dr. De Benedetto or other team members (e.g. coordinator, nurse, co-investigator) will be 
meeting directly with the subjects in a private suite. The consent form will be discussed with the 
potential subject. Time allotted to consenting will be dependent on the subjects’ needs, 
questions, and comprehension of the information in the consent form.  Each subject will be 
encouraged to read the consent form on his/her own and ask any specific questions. At the time 
of consent, subjects will be offered the option to provide permission to be contacted in the future 
regarding this and other dermatologic studies.  Those who provide permission for future contact 
will be added to the IRB201600411 approved database. 
Subject capacity  
We will not be recruiting subjects incapable of giving informed consent. 
Subject/representative comprehension  
The subject’s capacity to comprehend the information in the consent form will be assessed by 
asking questions about the content and encouraging the subject to describe briefly the study 
procedures. 
Documentation of consent  
The consent will be documented by signing the consent form by both the study subject and the 
person obtaining consent. A copy of the consent form will be provided to the subject. 
Costs to the subject  
Procedures performed during the study will be at no cost to the subject. 
Payment for participation  
Subjects that agree to participate in the study will receive compensation for their time:  $25.00 


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for the screening visit.  Each study visit will be $45.00 and an additional $45.00 for the optional 
biopsy. The Final visit (Follow up Visit) will also be $25.00. For a total of up to $275.00 including 
the 2 biopsies or $185.00 without the biopsy if all visits are completed.  UF VISA cards will be 
used for the reimbursement. Payments will be issued to VISA card within 7 business days of 
completed study visit. 
 
Potential benefits to the subjects  
There are no benefits for the individual participant. The investigational medication may 
temporally improve or worsen the lesion in the target area of application. The nature of this pilot 
study does not promise benefit for the individual. We hope that this research will lead to a better 
understanding of atopic dermatitis pathogenesis and pave the way for development of topical 
medications that aim to repair skin barrier and skin driven inflammation.  
 
 
Figure 1: Multi probe System MPA5 – Courage & Khazaka (Germany) and Aquaflux (Biox, 
London UK).  
 
 
 
Figure 2: D500–D-squame® pressure instrument and D-squame® - CuDerm (Dallas, TX) 
 
 
                                                          
i NEJM 2008 Apr 3;358(14):1483-94 
ii JAAD 2002 Mar;46(3):361-70 


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iii JID 2009 Aug;129(8):1892-908 
iv J Clin Invest. 2012 Feb;122(2):440-7 
v J Eur Acad Dermatol Venereol 2013;27:239-42 
vi BJD 2006; 154(4):719-25 
vii Lancet 2012;380:2197 
 
viii Wounds, 15:315-323, 2003 
ix Biol Res Nurs. 2010 Apr;11(4):336-44 
x JID 2012;132:1435 
xi J. Periodontology 2015;2:10 
xii Arch Dermatol. 1994 Nov;130(11):1402-7 
xiii Br J Dermatol, 2011. 165(2): p. 329-34 
xiv Br J Dermatol. 2015 Aug;173(2):316-7. 
xv Allergy, 2006. 61(3): p. 375-81. 

ICF_000.pdf: 
IRB #201601657 
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IRB Version: 10/19/2011
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INFORMED CONSENT FORM
to Participate in Research, and
AUTHORIZATION 
to Collect, Use, and Disclose Protected 
Health Information (PHI)
INTRODUCTION
Name of person seeking your consent:
Place of employment & position: 
Please read this form, which describes the study in some detail. A member of the 
research team will describe this study to you and answer all of your questions.  Your 
participation is entirely voluntary.  If you choose to participate you can change your mind 
at any time and withdraw from the study.  You will not be penalized in any way or lose any 
benefits to which you would otherwise be entitled if you choose not to participate in this 
study or to withdraw.  If you have questions about your rights as a research subject, 
please call the University of Florida Institutional Review Board (IRB) office at (352) 273-
9600.   
GENERAL INFORMATION ABOUT THIS STUDY
1.
Name of Participant ("Study Subject")
___________________________________________________________________ 
2.
What is the Title of this research study?
A Phase 2, Exploratory Study to Investigate Safety and Efficacy of Doxycycline 
Monohydrate Hydrogel (NANODOX® HYDROGEL 1%) In Atopic Dermatitis
Study ID:IRB201601657   Date Approved: 11/29/2017   Expiration Date: 8/10/2018


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3.
Who do you call if you have questions about this research study?
Principal Investigator: Anna De Benedetto, MD – Department of Dermatology, UF 
Phone Number: (352) 594-1500, a 24-hour number that can be used after hours and 
on weekends and holidays 
Other research staff:  
Mary Bohannon, CCRA - Research Coordinator
Phone Number: (352) 594-1547
Email: mebohan@ufl.edu
Lenise Thomas, LPN - Research Nurse 
Gregory Schultz, PhD – Co-Investigator
Kiran Motaparthi, MD – Sub-Investigator
Kathryn Potter, MD - Sub-Investigator
Alex Owens, MD– Sub-Investigator
Jennifer Harb, MD  – Sub-Investigator
Jennifer Schoch, MD- Sub-Investigator
Bahram Dideban, MD- Sub- Investigator
Michael Montuno, MD- Sub-Investigator
Sanjuana Rodriguez, PA-C- Sub-Investigator
Gina Martorana – EPIC specialist and technology support
Peter Nadeau – Laboratory Bioscientist 
4.  Who is paying for this research study? 
The sponsors of this study include University of Florida Clinical and Translational 
Science Institute, College of Medicine Department of Dermatology, and Alchem 
Laboratories Inc.
5. Why is this research study being done? 
Atopic Dermatitis (AD), also known as eczema, is the most common inflammatory 
skin disease, affecting about 17% of children and 6% adults in the United States of 
America.  AD is characterized by skin barrier disruption/open sores, an exaggerated 
inflammatory response to environmental triggers, susceptibility to skin bacterial 
infections and hard to control itch. The intense itch and skin infections contribute to 
the disease and are major drivers of the reduced quality-of-life. So far, AD treatments 
have targeted inflammation with the widespread use of topical (applied directly to the 
skin) and more intermittent use of systemic (taken by mouth or injection) 
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corticosteroids. Despite its high prevalence, effects on quality-of-life and economic 
burden – there are few effective treatments for AD. 
Doxycycline are tetracycline antibiotic, commonly used to treat inflammatory-
dermatologic conditions and are often prescribed as oral pill. Several studies in 
human and animal models have shown doxycycline has anti-inflammatory and pro-
healing properties, mainly by blocking activity of certain proteins in the skin.  
The purpose of this research study is to investigate the safety and clinical efficacy of a 
novel 1% topical Doxycycline Monohydrate (NanoDOX® Hydrogel 1%) in Atopic 
Dermatitis (AD).  This investigational drug has been approved by the FDA for use in 
this study but is not yet commercially available.  We are investigating whether the 
daily application of NanoDOX® Hydrogel 1% blocks activity of specific proteins 
(cutaneous proteases) in the skin in patients with AD and reduces severity of the 
disease, by restoring skin barrier function and reducing skin driven inflammation. 
Throughout the remainder of this form, NanoDOX® Hydrogel 1% will be referred to as 
Study Drug.  Importantly, during the study we will also monitor the anti-microbial 
activity of this product on AD skin, as colonization with Staphylococcal aureus is 
typically associated with disease severity. 
The study drug will be provided to you in single-dose package containing 1.5 cc of 
hydrogel with 1% nanodoxy (equal to 15mg Doxycycline). Of note, for systemic use 
doxycycline is taken orally at doses of 40 mg to 100 mg twice a day, for 2 weeks to 
several months; this is about 3-14 times the amount that is in the skin gel .   We want 
you to apply the study drug on the target area that will be described to you during 
your study examination.  This target area will include an area with an active dermatitis 
lesion and the surrounding area.  We will be testing both areas throughout the study. 
You are being asked to be in this research study because you have previously been 
diagnosed with atopic dermatitis and may meet the inclusion criteria.
WHAT CAN YOU EXPECT IF YOU PARTICIPATE IN THIS STUDY?
6.   What will be done as part of your normal clinical care (even if you did not 
participate in this research study)? 
All the study procedures will be for research purpose only. We will schedule the 
research visits at a different time than your routine dermatologic visits. 
7.  What will be done only because you are in this research study? 
If you agree to be in this study, we will ask you to come to the Department of 
Dermatology for at least four visits. 
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Pre-Screening visit (optional, <28days from Day 0): 
This visit will take approximately 30 minutes.  We will review this consent form with 
you. If you agree to participate, you will be asked to sign this consent form.  A copy of 
the form will be given to you.  We will review your medical history medical history 
including medications and you will have a dermatology exam (a physician from the 
study team will look at your skin).  If you meet the inclusion criteria, the use of certain 
medications will be discussed with you, including stopping the use of these 
medications if necessary until your participation is complete.  You will be scheduled to 
return to the clinic for Visit 1.
Visit 1 (Day 0): This visit will take approximately 2 hours.
At Visit 1, we will review the consent form with you and address any questions or 
concerns that you may have.  If you continue to agree to participate in this study, we 
will confirm that you still meet the study requirements.  The following study related 
procedures will be performed as part of this visit.
1) Urine Pregnancy test for woman of childbearing potential 
We will ask you to provide a urine sample for a urine pregnancy test. This test   
will need to be negative to be enrolled on the study.  The study doctor will                      
counsel you on acceptable birth control measures to use throughout treatment   
period (28 days) and until 30 days after stopping the study drug.
2) General History, Physical Exam, and Skin Exam (including review of medications)
         We will do a short exam to make sure that you qualify for the study.  We will   
         ask you to wear a gown for the skin exam. This will take about 15 
         minutes.  During this exam, we will ask you questions about your skin.  The             
         Doctor will score different areas of your skin for redness, scratch-marks, 
         thickness and other clinical signs of skin disturbance and signs of eczema 
        (atopic dermatitis).  You will be asked to describe your skin’s itchiness.
3) Target Area Identification
An area of your body will be identified as the target area to be treated with the 
study drug and skin biopsy locations will be selected. Arms will be the preferable         
areas if lesions are present, otherwise legs or torso areas may be chosen.
 4) Digital Photographs
           We will take digital photographs of the target area and area used for biopsy.
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5) Skin Barrier Measurements
           The study team will apply special tools/probes on your skin to measure your 
           skin.  These tools measure water loss from the skin: 
             TransEpidermal Water Loss, (TEWL), the pH of the surface of skin, and how 
              moisturized the skin may be (Stratum Corneum Hydration).  This procedure 
              will be repeated at each visit. We call this testing Skin Barrier Measurements. 
6) Tape Stripping
           The study team will also place circular tape (approximately the size of a        
            quarter) onto your skin. This tape has a special adhesive (glue-like) material 
            that will remove some of the cells of your skin.  Tapes will be placed and 
            removed multiple times one after another to remove the uppermost layer of    
            cells and debris that may be on the surface of your skin. These tapes will be    
            placed in an area of an eczema lesion and in an area that does not have a    
            lesion. We will repeat the TEWL skin barrier measurement tool on the areas 
            where the tape was removed.   
7) Skin Swab
          The study team will use a cotton swab to collect a sample from the surface of     
           your skin in the  target lesion area. 
8) Optional Skin Biopsy
           A  5mm punch biopsy approximately the size of pencil eraser  will be taken    
           from an area of  skin that is similar to the location of the target lesion. For 
           example, if the target lesion is on the right arm, we would ask to take the first 
           biopsy from the left arm. The area will be numbed with numbing medicine 
           before to reduce any pain in the area. The numbing medicine will be injected 
           into the skin. You will have the option to have this biopsy performed at 
           Visit 3 at the same time as the optional post-treatment biopsy.
9) Blood Draw
           Approximately 1 teaspoon (5mL) of blood will be drawn from a vein.
In the Study procedures & method section of this consent form you will find more 
detailed information about the study procedures. Please feel free to ask any of the 
study team member any question you might have.
10) Study Drug Instructions
        The study team will give you enough study drug until your next visit                  
         (approximately 14 day supply)
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          - Instructions will be provided on how and where to apply the product including   
            an at home diary to be completed and special instructions for the morning of   
            upcoming appointments. The target lesion location will be identified on a body   
            map for reference.
          - You  will be instructed to keep the study drug refrigerated (40°F); We will              
            will be provided with a cooler and ice pack for transport of the study drug   
            so that it remains in a refrigerated environment. 
          - You will be asked to bring the cooler with you to your next visit and to return 
            the study drug packages, empty or unused.
At home, we will ask you to apply the study drug once daily at bedtime on the chosen 
target lesion and on the surrounding area (to cover an area of approximately the size 
of an index card). In the morning rinse the area with water and soap to remove 
possible leftover study drug. When taken orally, doxycycline can make your skin more 
sensitive to the sun, during the day when you are exposed to sun make sure you 
keep the area covered or apply sunscreen (SPF 30 or higher).
If you take any topical treatment for your current skin condition you will be asked to 
discontinue the use of those medications only in the target lesion and perilesional area 
for one week before starting the study (washout period) and until study completion. 
During the study, you will be allowed to stay on anti-histamine and any topical 
treatment in other lesional areas (except for the target area) as long as the dose of 
medication does not change. If you have any worsening change in the target area 
(intense itch, increase redness, pain or oozing) you will be asked to contact the study 
doctor using the 24-hour number provided.  The study doctor will discuss with you 
what rescue medication you can use (e.g. topical steroid that you have used before 
the study).  You may be asked to return to the clinic. 
Visit 2 (Day 14 +/-2): This visit will take approximately 1 hour.
1) Review subject diary and address any questions, concerns, or missed doses
2) Brief Physical Exam and Skin Exam
3) Suture removal at pre-treatment biopsy site, if applicable
4) Digital photographs of the targeted area
5) Skin Barrier Measurements: TEWL, +/- pH and SC hydration
6) Repeated tape strippings and repeat TEWL.
7) Dispense the study drug for two following weeks and provide at home diary with 
study instructions and next visit date.
In case of complete resolution of the treated area at V2, post treatment biopsy and 
swab and Venous blood draw will be performed at this visit (instead V3) and subject’s 
final visit will be performed at Day 28.
Visit 3 (Day 28 +/-2): This visit will take approximately 1 hour and 30 minutes.
1) Review subject diary and address any questions, concerns, or missed doses
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2) Brief Physical Exam, and Skin Exam 
3) Digital photographs of the targeted area
4) Skin Barrier Measurements: TEWL, +/- pH and SC hydration
5) Tape strippings and repeat TEWL 
6) Skin swab of treatment area
7) 2 Optional skin biopsies (5 mm punch) 1) from treatment site and 1) from not 
treated site
8) Venous blood draw
9) Provide at home diary with study instructions and next visit date
Visit 4 (Day 42 +/-5): This visit will take approximately 45 minutes.
1) Review subject concerns or questions since last visit
2) Brief Physical Exam and Skin Exam
3) Suture removal at biopsy site
4) Take digital photographs of the targeted area
5) Skin barrier Measurements: TEWL, +/- pH and SC hydration
6) Repeated tape strippings and repeat TEWL 
7) Discharge from study, including counseling on birth control measures through 30 
days after last application of study drug.
Study procedures & method-
Clinical Score: Subjects will be assessed by:
1)  Investigator Global Assessment (IGA), which will provide information of the overall 
disease (four point scale: clear, mild, moderate, severe).
2) Eczema Area and Severity Index (EASI), It is the sum of the intensity scores for 
four signs (0 to 3): erythema, induration (hardening), excoriation (scratch-like marks 
on the skin), lichenification (thickening of the skin) and it is recorded for targeted 
treatment areas as well as four regions of the body (i.e., head, trunk, lower and upper 
extremities). The presence or absence of skin irritation will be noted at each study 
visit.
 
3) Pruritus Scale (5-D): The pruritus (itch) categorical scale is a 4-point scale 
commonly used in clinical studies of AD.  The scale is rated as follows: 
0: absence of pruritus; 1: mild pruritus (occasional slight itching/scratching); 2: 
moderate pruritus (constant or intermittent itching/scratching that does not disturb 
sleep) and 3: severe pruritus (bothersome itching/scratching that disturbs sleep).
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4) Digital photographs: A digital picture will be taken with a dedicated digital camera. 
The photographs will be labeled with the subject’s study ID and date. Photographs will 
not include identifying information (e.g. facial features, tattoo, etc.). Photographs will 
be taken at a distance for easy identification of the anatomical area and closer to 
better capture clinical changes. Digital photographs will be used to record the location 
and monitor the size of target lesions.  At conclusion of the study, two medical doctors
on the study team will be asked to score (0-4 scale, clear, mild, moderate, severe) in a 
blind fashion (i.e., photographs will be de-identified and presented randomly/ not 
inchronologic order). This would allow objective confirmation of the clinical score taken 
during the study.  
Skin swab: Skin swabs will be collected for microbiologic analysis to look for bacteria 
on your skin, including S. aureus spp. and to determine antibiotic sensitivity. Skin 
swabs are performed by swiping and rolling a sterile cotton-tipped applicator 4-5 
times across the target area.  Swabs will be obtained from target lesion areas pre and 
post treatment. These swabs may be repeated as needed throughout the study to 
monitor bacterial growth.
Optional Skin biopsy: The biopsy will consist of removing a piece of skin with a 
sterile 5-mm skin biopsy punch. One skin biopsy sample (5 mm ≈ pencil eraser size) 
will be obtained within the surrounding area of the target lesion (if possible) or on the 
contralateral side before and after treatment with study drug.  Biopsy will be 
performed after injecting a local anesthetic (Lidocaine +/- epinephrine) to minimize 
pain and bleeding. At the biopsy sites, one or two sutures will be placed to ensure 
better healing, minimize blood loss and to provide a more aesthetic scar formation. A 
pressure bandage will be applied to the biopsy site to minimize the risk of bleeding 
and infection. We will provide each subject with a wound care instruction sheet.
Each biopsy will be used for analysis of proteins that are typically upregulated in 
inflammatory skin. Secondarily, we will evaluate changes in inflammatory and pro-
inflammatory pathways in study-drug treated and non-treated skin. The biopsies are 
optional.  
Tape stripping: The most superficial layers of the skin will be collected by tape 
stripping using D-squame and Cuderm™ tape.  Tapes will be applied and removed 
immediately one after the other: 0, 5, 10, and 15 tape-strippings. This is a well-
established method used in clinical research to gently disturb the skin barrier. The first 
tape will be discarded to eliminate dirt and remnants of skin products. Each tape will 
be gently pressed against the skin using a standardized pressurizer instrument (D-
squame). Non-lesional skin samples will be collected from the volar side of the 
forearm and lesional skin samples will be collected from the target area in an easily 
accessible area, such as arms or lower legs. 
This method collects most superficial layer of the skin to analyze for the presence of 
proteins important in skin inflammation.
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Skin barrier measurements: Transepidermal water loss (TEWL), pH and skin 
hydration measurements will be obtained on treatment area at a non-lesional site and 
on a site of inflammation. For each of the specific measurements, a probe will be 
gently applied on the skin surface for up to 90 seconds. We will perform all 
measurements in a climate-controlled examination room with consistent temperatures 
humidity after the patient has become comfortable in the room to ensure that 
perspiration due to stress or acclimatization does not alter the TEWL. TEWL will be 
measured at baseline and after tape stripping at each visit. Optional measurements: 
Skin hydration and surface pH will be assessed on non-lesional and lesional skin 
before tape stripping at each visit when equipment is available. These measurements 
should provide data to determine if the treatment has an effect on skin barrier 
integrity.
Blood Sample: A blood sample (4 ml, approximately 1 teaspoon) will be obtained to 
evaluate biomarkers of disease severity.  This blood sample will be drawn at 2 visits: 
Day 0 before treatment and Day 14 (if lesion is resolved) or Day 28 after treatment 
period is complete.
Test Results: Results of the tests will not be shared with you since it is not known 
what importance they would have for your medical care.  Knowing the test results 
would not change your medical care.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  This Web site will not include information that can identify you.  
At most, the Web site will include a summary of the results. You can search this Web 
site at any time. 
8.
How long will you be in this research study?
This study consists of up to 5 visits, including the screening visit, during an 
approximate 70-day time period. The study treatment period is expected to be 42 
days (6 weeks).  Some subjects may complete the study in approximately 28 days if 
resolution of lesion is noted at the 14-day visit.
9.
How many people are expected to take part in this research study?
We hope 15 subjects will complete all protocol-required visits. Up to 30 subjects will 
be recruited from the University of Florida Department of Dermatology. 
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WHAT ARE THE RISKS AND BENEFITS OF THIS STUDY AND 
WHAT ARE YOUR OPTIONS?
10. What are the possible discomforts and risks from taking part in this research 
study?
Risks Associated with Digital Photographs
There are no known risks for the digital photographs. The image will not include 
identifying features and will be labeled with study subject ID and date. Photographs 
will be taken with a dedicated camera, stored on a secure server and transferred into 
secure database.
Risks Associated with Barrier Assessments
There are no known risks for the barrier assessments. 
Risks Associated with Tape Stripping
The risks associated with tape stripping, theoretically, include the rare possibility of an 
allergic reaction to the tape and infection.  The tape used is approximately the size of 
a quarter and is a gentle adhesive specifically designed for this measurement.  Each 
tape is removed 10seconds after application, thus the risk of reaction is extremely 
low.  We will exclude study subjects with known allergy to tapes or adhesive material. 
In previous and ongoing studies involving tape stripping, it has been noted that a very 
mild erythema may develop immediately after a series of tape stripping on one 
localized area of skin, presumably due to the mild mechanical disturbance.  The 
erythema is expected to resolve within 12 hours without further effect.  The risk of skin 
infection is extremely low since only superficial skin layers are removed.  Subjects will 
be provided with wound care information and a department phone number to contact 
should they have any concerns. 
Risks of blood draws
The risks of drawing blood from a vein include discomfort at the site of puncture; 
possible bruising and swelling around the puncture site; rarely an infection; and, 
uncommonly, faintness from the procedure. 
Subjects will be encouraged to drink plenty of water prior to the blood draw. 
Phlebotomy will be performed on the interior side of the elbow to minimize pain and 
bruising. Subjects will be seated during the blood draw to minimize dizziness and any 
risk of falling. Pressure will be applied to the site after the draw and a Band-Aid will be 
applied to minimize the risk of bleeding and infection.
Risks of punch biopsy and injection of local anesthesia
The biopsies will be no larger than 5 mm in diameter (about a pencil eraser head). At 
the biopsy site, one or two sutures will be placed to ensure better healing, minimize 
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blood loss and to provide a more aesthetic scar formation. A pressure bandage will be 
applied to the biopsy site to minimize the risk of bleeding and infection.  A small scar 
will remain at the site. The scar will be smaller than the initial biopsy but may also be 
hypo- or hyper-pigmented. Sutures will be removed in 14 days. The risks of this 
procedure include adverse reaction to anesthesia (lidocaine), pain, bleeding, infection 
and hypertrophic scars. Biopsy will be performed after injecting a local anesthetic to 
minimize pain. Patients with a history of Novocain or lidocaine allergy or a history of 
keloid formation will not be allowed to participate in order to minimize the risk of 
adverse reactions. Written wound care instruction will be provided for at home care 
after the procedure. In case of increased redness, pain or oozing of the sites subjects 
will be instructed to call the dermatology department and if appropriate, subjects will 
be asked to come to clinic in the next 24-48 hours for wound check.
Risks of NANODOX® HYDROGEL 1% ®
Some patients may experience some irritation from the NANODOX® hydrogel 
especially in areas of open skin from scratching. Subjects may experience local 
irritation including redness, pain, stinging or burning sensation in the area. Some 
subjects might also experience a blistering rash or swelling. Some subjects may 
experience increased dryness from the hydrogel formulation.  All patients will be 
advised to moisturize in the morning and use gentle body wash to minimize these 
potential side effect. Preclinical studies have shown that over time (12-24 hours) the 
color of leftover products in the package might change from a white transparent tone 
to a more yellow-brown color. Change in color has not been associated with change 
in efficacy. To minimize risk of skin discoloration we will advise the subjects to rinse 
off the site in the morning. 
As with any antibiotic, long term use might increase the risk of  developing 
antibacterial resistance. 
Subjects with sensitivity to doxycycline might develop an allergic drug reaction, which 
could vary from local irritation to more severe systemic reaction. Subjects with known 
sensitivity/allergy to tetracycline will not be enrolled in the study.
In case of any abnormal reaction, we will instruct the subjects to call the dermatology 
office and stop using NanoDOX® Hydrogel 1% until discussing symptoms with study 
team. 
Risks to children or pets are not known and subjects will be instructed to keep the 
products out of reach from children and pets. Because this is an investigational 
medication/formulation, some side effect may not yet be known. Any adverse reaction 
will be accounted.
Based on preliminary data, we do not anticipate any complications associated with 
the use of topical doxycycline. 
Risks related to Oral Doxycycline
Common skin reactions with taking 
oral doxycycline include: 
•Redness 
•Swelling 
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•Blistering rash 
Common 
allergic 
reactions 
with 
taking oral doxycycline include: 
•Hives 
•Shortness of breath 
•Swelling of the face, lip, tongue, or     
    throat 
Common systemic reactions with 
taking oral doxycycline include: 
•Headache 
•Dizziness 
•Fever 
•Chills 
•Rash 
•Nausea 
•Vomiting 
•Diarrhea 
•Thrush 
•Vaginitis 
General Risks
When participating in any research study there is a possibility for invasion of privacy 
or breach of confidentiality. 
Property damage risks
Objects in contact with the study drug may have discoloration (e.g. bedding, towels, 
and clothes). Subjects are advised to be careful handling the opened study drug 
packages and to rinse the excess of product from their skin if they observe change in 
color to minimize the likelihood of stain on towels, rugs or other clothing.
Reproductive Risks
The effects of topical doxycycline on an unborn fetus or nursing (breast-feeding) 
infant are unknown. It is possible that use of the study drug may be associated with 
unanticipated risks to a pregnancy or fetus. Women of childbearing potential will be 
counseled to use acceptable birth control methods. Women will not be allowed to 
participate in this study if they are pregnant, become pregnant, or are nursing an 
infant.
Researchers will take appropriate steps to protect any information they collect about 
you.  However, there is a slight risk that information about you could be revealed 
inappropriately or accidentally.  Depending on the nature of the information, such a 
release could upset or embarrass you, or possibly affect your insurability or 
employability.  Questions 17-21 in this form discuss what information about you will 
be collected, used, protected, and shared.
This study may include risks that are unknown at this time.
Participation in more than one research study or project may further increase the risks 
to you.  If you are already enrolled in another research study, please inform Dr. Anna 
De Benedetto or one of the research team members listed in question 3 of this form at 
(352) 594-1547 or the person reviewing this consent with you before enrolling in this 
or any other research study or project.
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Throughout the study, the researchers will notify you of new information that may 
become available and might affect your decision to remain in the study. 
If you wish to discuss the information above or any discomforts you may experience, 
please ask questions now or call one of the research team members listed in question 
3 in this form.
11a. What are the potential benefits to you for taking part in this research study?
There are no benefits for the individual participant. The investigational medication 
may temporally improve or worsen the lesion in the target area of application. The 
nature of this pilot study does not promise benefit for the individual. 
11b. How could others possibly benefit from this study?
We hope that this research will increase our understanding of AD and hopefully this 
will lead to development of new therapeutics aiming at repairing skin barrier and skin 
driven inflammation.  
11c. How could the researchers benefit from this study?
In general, presenting research results helps the career of a scientist. Therefore, the 
Principal Investigator Dr. Anna De Benedetto and co-Investigators may benefit if the 
results of this study are presented at scientific meetings or in scientific journals.
12. What other choices do you have if you do not want to be in this study? 
Your participation in this study is voluntary.  You may decide not to participate or you 
may leave the study at any time.  Your decision will not result in any penalty or loss of 
benefits to which you are entitled.
13a. Can you withdraw from this study?
You are free to withdraw your consent and to stop participating in this study at any 
time.  If you do withdraw your consent, you will not be penalized in any way and you 
will not lose any benefits to which you are entitled.  If you decide to withdraw your 
consent to participate in this study for any reason, please contact Dr. Anna De 
Benedetto by calling (352) 594-1547 or one of the research team members listed in 
question 3 of this form.  They will tell you how to stop your participation safely. If you 
experience adverse drug reactions, you will be followed until resolution or stabilization 
of the adverse event, or until you start a new treatment regimen.  If you are removed 
from the study for unacceptable adverse events, you will be followed in the same 
manner.  In addition, you may have to undergo additional tests, based on the 
condition of your health.
If you have any questions regarding your rights as a research subject, please call the 
Institutional Review Board (IRB) office at (352) 273-9600.
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13b.If you withdraw, can information about you still be used and/or collected?
If you withdraw from the study samples and data already collected from you may still 
be used for research.  Additional clinical data or samples will not be collected from 
you. 
13c. Can the Principal Investigator withdraw you from this study? 
You may be withdrawn from the study without your consent for the following reasons:

Your disease worsens, you experience unacceptable toxicity, or you decide to 
withdraw from the study.

Discovery of unexpected, unacceptable risks to participants.

Your failure to follow the study doctor’s instructions.

You become pregnant.

If it is in your best interest.

If you do not later consent to any future changes that may be made in the 
study plan.
WHAT ARE THE FINANCIAL ISSUES IF YOU PARTICIPATE?
14. If you choose to take part in this research study, will it cost you anything?
Study Drug
NanoDOX® Hydrogel 1% will be provided at no cost to you while you are 
participating in this study.
Study Services
The Sponsor will pay for all services required as part of your participation in this 
study as described above in the question “What Will Be Done Only Because You 
Are In This Research Study”. If you receive a bill for these services, please contact 
Dr. Anna De Benedetto and the study team by calling (352) 594-1547
Items/Services Not Paid for by the Sponsor 
All other medical services provided to you that are not directly required by this study 
will be billed to you or your insurance company in the usual manner. 
15. Will you be paid for taking part in this study?
You will be paid for each completed study visit, $ 25 for screening and follow up visit, 
$45.00 each visit, and an additional $45.00 for each biopsy for a total of up to $275.00 
(2 biopsies) or $185.00 (without biopsies), according to the following schedule:
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Screening visit=$25 (if needed) 
Visit 1= $45(+$45 biopsy, or at Day28)= maximum of $90 
Visit 14d= $45 
Visit 28d= $45+$45post treatment biopsy+($45 for non-treatment biopsy, if not 
performed at Visit 1)= maxiumum of $135  
Visit 42d= $25 (if needed) 
Visa cards will be provided at Study Visit 1 and the cards will be loaded with the 
amount listed above within 7 business days of each completed visit.
If you are paid more than $75 for taking part in this study, your name and social 
security number will be reported to the appropriate University employees for 
purposes of making and recording the payment as required by law. You are 
responsible for paying income taxes on any payments provided by the study. If the 
payments total $600 or more or you are a nonresident alien, payment will be 
processed through the University of Florida Accounts Payable department and the 
University must report the amount you received to the Internal Revenue Service 
(IRS). The IRS is not provided with the study name or its purpose. If you have 
questions about the collection and use of your Social Security Number, please visit: 
http://privacy.ufl.edu/SSNPrivacy.html. 
Your payment for participation in this research study is handled through the 
University of Florida’s Human Subject Payment (HSP) Program.  Your information 
which will include your name, address, date of birth, and SSN (depending on 
amount of money you are paid) is protected.  Access to the (HSP) Program site is 
limited to certain staff with the assigned security role.  You will be randomly 
assigned a specific identification (ID) number to protect your identity.
The study team will provide you with an informational form called the Prepaid Card 
Facts document.  If you have any problems regarding your payment call the HSP 
Office (352) 392-9057.
University employees are no longer paid through the University payroll system.  
Instead, UF employees will be paid in a manner consistent with other participants in 
this research study.
16. What if you are injured because of the study?
If you are injured as a direct result of your participation in this study, only the 
professional services that you receive from any University of Florida Health Science 
Center healthcare provider will be provided without charge.  These healthcare 
providers include physicians, physician assistants, nurse practitioners, dentists or 
psychologists. Any other expenses, including Shands hospital expenses, will be 
billed to you or your insurance provider. 
You will be responsible for any deductible, co-insurance, or co-payments. Some 
insurance companies may not cover costs associated with research studies or 
research-related injuries. Please contact your insurance company for additional 
information. 
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The Principal Investigator will determine whether your injury is related to your 
participation in this study. 
No additional compensation is offered. The Principal Investigator and others 
involved in this study may be University of Florida employees. As employees of the 
University, they are protected under state law, which limits financial recovery for 
negligence.
Please contact Dr. Anna De Benedetto and the study team by calling (352) 594-
1547 or the Department of Dermatology triage nurse at (352) 594-1500 if you 
experience an injury or have questions about any discomforts that you experience 
while participating in this study.
17. How will your health information be collected, used and shared?
If you agree to participate in this study, the Principal Investigator or a research team 
member will create, collect, and use private information about you and your health. 
This information is called protected health information or PHI. In order to do this, the 
Principal Investigator needs your authorization.  The following section describes what 
PHI will be collected, used and shared, how it will be collected, used, and shared, 
who will collect, use or share it, who will have access to it, how it will be secured, and 
what your rights are to revoke this authorization. 
Your protected health information may be collected, used, and shared with others to 
determine if you can participate in the study, and then as part of your participation in 
the study.  This information can be gathered from you or your past, current or future 
health records, from procedures such as physical examinations, x-rays, blood or urine 
tests or from other procedures or tests.  This information will be created by receiving 
study treatments or participating in study procedures, or from your study visits and 
telephone calls.  More specifically, the following information may be collected, used, 
and shared with others: 

Complete past medical history to determine eligibility criteria 

Records of physical exams

Laboratory and other test results

Records about study medications or drugs

Your social security number [for compensation purposes]
This information will be stored in locked filing cabinets or on computer servers with 
secure passwords, or encrypted electronic storage devices. 
Some of the information collected could be included in a "limited data set" to be used 
for other research purposes.  If so, the limited data set will only include information 
that does not directly identify you.  For example, the limited data set cannot include 
your name, address, telephone number, social security number, photographs, or 
other codes that link you to the information in the limited data set.  If limited data sets 
are created and used, agreements between the parties creating and receiving the 
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limited data set are required in order to protect your identity, confidentiality, and 
privacy.
18. For what study-related purposes will your protected health information be 
collected, used, and shared with others?
Your PHI may be collected, used, and shared with others to make sure you can 
participate in the research, through your participation in the research, and to evaluate 
the results of the research study.  More specifically, your PHI may be collected, used, 
and shared with others for the following study-related purpose(s):

to study if the study drug is safe and well-tolerated in humans

to study whether the study drug has an effect on atopic dermatitis
Once this information is collected, it becomes part of the research record for this 
study.  
19. Who will be allowed to collect, use, and share your protected health 
information?
Only certain people have the legal right to collect, use and share your research 
records, and they will protect the privacy and security of these records to the extent 
the law allows. These people include:

the study Principal Investigator (listed in question 3 of this form) and research 
staff associated with this project.

other professionals at the University of Florida or Shands Hospital that provide 
study-related treatment or procedures.

the University of Florida Institutional Review Board (IRB; an IRB is a group of 
people who are responsible for looking after the rights and welfare of people 
taking part in research).  
20. Once collected or used, who may your protected health information be shared 
with?
Your PHI may be shared with:

The study sponsor, Alchem Laboratories will review your research records for 
quality assurance and data analysis purposes.  Alchem will not give out any 
information which will let researchers know who you are.

Alchem needs to review your PHI in order to analyze the information to find out 
whether the drug that is being tested if effective and to monitor your safety.

United States governmental agencies who are responsible for overseeing 
research, such as the Food and Drug Administration, the Department of Health 
and Human Services, and the Office of Human Research Protections.
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
Government agencies who are responsible for overseeing public health 
concerns such as the Centers for Disease Control and federal, state and local 
health departments.
Otherwise, your research records will not be released without your permission unless 
required by law or a court order. It is possible that once this information is shared with 
authorized persons, it could be shared by the persons or agencies who receive it and 
it would no longer be protected by the federal medical privacy law.  
21. If you agree to take part in this research study, how long will your protected 
health information be used and shared with others?
Your PHI will be used and shared with others until the end of the study.
You are not required to sign this consent and authorization or allow researchers to 
collect, use and share your PHI. Your refusal to sign will not affect your treatment, 
payment, enrollment, or eligibility for any benefits outside this research study. 
However, you cannot participate in this research unless you allow the collection, use 
and sharing of your protected health information by signing this consent and 
authorization.
You have the right to review and copy your protected health information.  However, 
we can make this available only after the study is finished.
You can revoke your authorization at any time before, during, or after your 
participation in this study.  If you revoke it, no new information will be collected about 
you.  However, information that was already collected may still be used and shared 
with others if the researchers have relied on it to complete the research.  You can 
revoke your authorization by giving a written request with your signature on it to the 
Principal Investigator.
Study ID:IRB201601657   Date Approved: 11/29/2017   Expiration Date: 8/10/2018


IRB #201601657 
Page 19 of 19
IRB Version: 10/19/2011
PI Version: Version 5_8November2017
SIGNATURES
As an investigator or the investigator’s representative, I have explained to the participant 
the purpose, the procedures, the possible benefits, and the risks of this research study; 
the alternative to being in the study; and how the participant’s protected health 
information will be collected, used, and shared with others: 
Signature of Person Obtaining Consent and 
Authorization
Date
You have been informed about this study’s purpose, procedures, possible benefits, and 
risks; the alternatives to being in the study; and how your protected health information will 
be collected, used and shared with others.  You have received a copy of this Form.  You 
have been given the opportunity to ask questions before you sign, and you have been 
told that you can ask   questions at any time.  
You voluntarily agree to participate in this study. You hereby authorize the collection, use 
and sharing of your protected health information as described in sections 17-21 above.  
By signing this form, you are not waiving any of your legal rights.
Signature of Person Consenting and Authorizing
Date
 
Study ID:IRB201601657   Date Approved: 11/29/2017   Expiration Date: 8/10/2018