Topical Collagen Powder as a Wound Healing Adjuvant for Acute Full-thickness Punch Biopsy-induced Human Wounds: a Pilot Study
Phase: NA
Conditions: Wound of Skin, Wound Heal
Sponsor: Adam Friedman

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Version Date: January 29, 2018 
Topical collagen powder as a wound healing adjuvant for acute full-thickness 
punch biopsy-induced human wounds: a pilot study 
 
 
 
 
 
 
STUDY PROTOCOL 
 
 
 
 
 
 
 
 
GWU IRB # 121745 
 
PRINCIPAL INVESTIGATOR: 
 
Adam Friedman, MD 
Associate Professor of Dermatology 
George Washington University 
 
Medical Faculty Associates 
2150 Pennsylvania Avenue, NW  
Washington, DC 20037  
(202) 741-2625 
 
 
 
 

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TABLE OF CONTENTS 
 
1. 
STATEMENT OF HYPOTHESIS AND OBJECTIVES 
 
2. 
BACKGROUND, SIGNIFICANCE, AND RATIONALE 
 
3. 
RESEARCH DESIGN AND METHODS 
 
3.1 
OVERVIEW OF DESIGN 
 
3.2 
SAMPLE SIZE, INCLUSION AND EXCLUSION CRITERIA 
 
3.3 
SCREENING PHASE 
 
3.4 
TREATMENT PHASE 
 
3.5 
STUDY COMPLETION AND WITHDRAWAL CRITERIA 
 
3.6 STRENGHTS AND LIMITATIONS OF PROPOSED RESEARCH 
 
4. 
DATA VARIABLES, COLLECTION, AND EVALUATION 
 
4.1 
DATA VARIABLES 
 
4.2 
DATA COLLECTION 
 
4.3 
STATISTICAL CONSIDERATIONS 
 
5. 
HUMAN SUBJECTS PROTECTION 
 
5.1 
SUBJECT SELECTION 
 
5.2 
RISKS AND BENEFITS 
 
5.3 
CONFIDENTIALITY 
 
5.4 
ADVERSE EVENTS AND SAFETY MONITORING 
 
6. 
REFERENCES 
 
 

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1. STATEMENT OF HYPOTHESIS AND OBJECTIVES: 
 
Surgical procedures are an essential piece of a dermatologist’s practice. In fact, it has been 
reported that dermatologists perform over 25 million minor surgical procedures annually. A 
major focus of these procedures is to restore the integrity of the skin while minimizing scarring 
and potential complications. With dermatologic surgeries being so numerous, there is much 
discussion about how to optimize post-surgical wound care while decreasing potential barriers to 
healing. Recent advances in wound therapy have resulted in the development of advanced wound 
care therapies, such as collagen-based dressings, for use as adjunctive therapies to combat the 
molecular defects present in wounds. 
 
We have designed a pilot study investigating the efficacy of NuvagenTM (collagen powder) in 
treating skin punch biopsy wounds. The objectives of the study are as follows:   
 
Primary objective: 
 
1. To evaluate the effect of NuvagenTM (collagen powder) on complete wound healing using 
punch biopsy sites as an acute full-thickness human wound model based on clinical 
wound closure. 
2. To evaluate the effect of NuvagenTM (collagen powder) on complete wound healing using 
punch biopsy sites as an acute full-thickness human wound model based on histology of 
wound site at 4 weeks following injury. 
 
2. BACKGROUND, SIGNIFICANCE, AND RATIONALE 
  
Wound healing is complex process which requires the restoration of hemostasis, inflammation, 
proliferation, and remodeling, all of which work in concert to repair the damaged skin barrier in 
acute wounds.1,2 Recent advances in wound therapy have resulted in the development of 
advanced wound care therapies, such as collagen-based dressings, for use as adjunctive therapies 
to combat the molecular defects present in wounds. 
 
Collagen is a naturally occurring protein that comprises three-quarters of the weight of human 
skin.3  Fibroblasts synthesize collagen molecules, which are composed of three polypeptide 
chains that together form a triple-helical structure, allowing covalent cross-linking and formation 
of larger fibrils and fibers.4 Collagen’s unique structure makes it an essential component of the 
extracellular matrix (ECM), providing remarkable tensile strength and structural support to skin 
and other connective tissues.4–6 During normal wound healing, collagen acts as a scaffold for 
cellular ingrowth and organized collagen deposition.5,7 In addition, proteases that degrade native 
collagen release polypeptide fragments that act as chemotactic molecules to recruit inflammatory 
mediators, promote keratinocyte migration, and stimulate the proliferation of fibroblasts and 
subsequent collagen deposition.5,7,8 
 
Powdered or fractionated collagen products are developed through a proprietary process that 
involves the breakdown of natural collagen into smaller components.5,7,9 These collagen particles 
exhibit minimal cross-linking and are hypothesized to quickly replace degraded collagen 
fragments by bypassing enzymatic breakdown within the wound environment. Furthermore, 

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powdered collagen can act as a signaling molecule directly upon application, recruiting 
inflammatory cells and fibroblasts and supporting keratinocyte migration and ECM 
production.10,11 
 
Additionally, collagen powders have the potential to satisfy many requirements of an ideal 
adjunctive wound therapy. Collagen is biodegradable, non-toxic, and naturally biocompatible 
with low antigenicity.3 Collagen itself promotes thrombosis and hemostasis while having 
hydrophilic properties useful for absorbing fluid in exuding wounds and maintaining moisture 
balance.12,13 Collagen is also a poor culture medium and can be left in wounds without risk of 
enhancing bacterial growth.14 Lastly, collagen powders are easy to apply and are indicated for 
use in most wound types, including infected wounds.  
 
We have designed a pilot study to investigate the effect and potential utility of topical 
NuvagenTM (collagen powder) on the rate and quality of wound healing in healthy volunteers 
using the punch biopsy method. After inducing an acute full-thickness wound, the rate of 
complete healing of a wound treated with topical NuvagenTM (collagen powder) will be 
compared to the rate of complete healing of a wound treated with primary closure with sutures, 
the current gold standard. Qualification and semi-quantification of histologic and 
immunohistochemical markers will be used to assess the maturity and structural stability of the 
wound bed. Positive findings would suggest that NuvagenTM (collagen powder) may be capable 
of stimulating the healing of acute wounds in a similar or even superior manner to primary 
closure, suggesting collagen powder may be used in place of sutures, and encouraging further 
studies to characterize its therapeutic potential in dermatologic surgery. 
 
3. RESEARCH DESIGN AND METHODS 
 
3.1 Overview of Design 
 
All participants will be patients that have been screened at the Department of Dermatology at the 
George Washington Medical Faculty Associates. Individuals taking part in the study will meet 
all of the inclusion criteria and none of the exclusion criteria (see Section 3.2). After completing 
the screening phase, subjects will receive 2 punch biopsy wounds on the thighs of each leg in 
their first study visit. Prior to dressing the wounds, 1 wound will be treated with primary closure, 
while the other will be treated with NuvagenTM (collagen powder). Each wound will continue to 
be treated with the treatment designated in visit 1 (primary closure or collagen powder) for the 
duration of the 12-week study. After visit 1, patients will be provided with instructions and 
supply for daily self-administration of NuvagenTM (collagen powder) for the wound designated 
for collagen powder treatment. Subjects will return weekly for 2 weeks, for suture removal if 
needed, photographs, wound measuring, assessment of healing, assessment of adverse events, 
and determination for need of further treatment with NuvagenTM (collagen powder). Subjects will 
then return at week 4 for 2 additional punch biopsies at the same sites wounded at the first visit, 
and will be provided with similar treatment instructions as they were provided in week 1. 
Patients will return in 2 weeks (visit 5) for suture removal, photographs, wound measuring, 
assessment of healing, assessment of adverse events, and determination for need of further 
treatment with NuvagenTM (collagen powder). The last study visit will be a 6 weeks after visit 5, 

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during which wounds will be measured and assessed for healing, while subjects will be 
photographed and assessed for adverse events. 
 
Study Population 
 
3.2 Sample Size, Inclusion and Exclusion criteria 
  
We will enroll a total of 8 patients for this study. The inclusion and exclusion criteria for the 
study are as follows: 
 
Inclusion criteria: 
• Outpatient, male or female subjects of any race, 18-75 years of age 
• Able to understand the requirements of the study and sign Informed Consent/HIPAA 
Authorization forms 
• Patients willing to refrain from using topical medications to punch biopsy sites 
• Patients who are willing to follow protocol instructions and return for follow-up visits 
• Patients that are able to give signed informed consent for the study 
 
Exclusion: 
• Patients less than 18 years and greater than 75 years of age 
• Patients that have any medical or skin condition that could impair wound healing 
• Patients that have used systemic medications that suppress the immune system within 5 
half-lives (if known), or 2 months of enrollment (i.e. corticosteroids) 
• Patients that have applied topical steroids to the thigh(s) in the 2 weeks prior to 
enrollment 
• Patients that are currently participating in an investigational study of a drug or device or 
have participated within 4 weeks of enrollment 
• Patients that in the opinion of the investigator demonstrate evidence of unwillingness or 
inability to follow instructions or to complete the study 
• Patients currently using systemic antimicrobials 
• Patients with a history of diabetes mellitus 
• Patients with a history of bleeding disorders or concomitant treatment with aspirin or  
anticoagulants (including heparin, low molecular weight heparin, warfarin, fondaparinux, 
or rivaroxaban) 
• Patients with a history of keloids or hypertrophic scars 
• Patients with other conditions considered by the investigator to be reasons for 
disqualification that may jeopardize subject safety or interfere with the objectives of the 
trial (e.g., acute illness or exacerbation of chronic illness) 
• Patients with a known allergy or sensitivity to any component of the test medication 
(including bovine and/or collagen products) or local anesthetic agent used 
• Current or previous users of tobacco products 
• Recent alcohol or drug abuse is evident 

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• Pregnant females or nursing mothers. Eligible women of reproductive age will be 
required to have a negative urine pregnancy test at screening. They will also be required 
to be on at least 1 reliable form of effective birth control [examples: barrier method 
(condoms, diaphragm), oral, injectable, implant birth control or abstinence] during the 
course of this study and 30 days following the last treatment period. 
 
3.3 Screening Phase 
 
Prior to wounding and treatment, potential participants will be evaluated for study eligibility. All 
inclusion and exclusion criteria must be met prior to study entry and enrollment. 
 
The patient’s first visit will comprise both screening and wounding. During the screening phase, 
after obtaining signed informed consent, subject’s personal data will be recorded. Data will 
include age, gender, medical and medication history and skin type. The physical examination 
will be performed and vital signs will be obtained. If the subject qualifies, visit 1 procedures will 
follow in the same visit. 
 
3.4 Treatment Phase 
 
On the first visit, eligibility criteria will be confirmed. Investigators will select 1 area on each 
anterior, proximal thigh of each volunteer where one 4 mm punch biopsies will be performed. 
The 2 areas will be cleansed using an alcohol swab, and anesthetized using 1 mL of 2% lidocaine 
with epinephrine. An Integra Miltex 4.0 mm Standard Biopsy Punch instrument will be used to 
create 2 full-thickness wounds, one on each thigh on each leg. Hemostasis will be obtained using 
Aluminum Chloride 20%, application of pressure, and gauze. Each wound will be photographed 
with a measurement instrument and then cleaned with normal saline prior to treatment. One 
wound will be selected for treatment with collagen, while the contralateral wound will undergo 
primary closure with sutures (1-2 epidermal sutures, 4-0 ProleneTM Polypropylene Sutures, 
Ethicon, Somerville, NJ). 
 
The wound selected for collagen treatment will receive 1 gram of topical NuvagenTM (collagen 
powder) directly on the wound with pressure applied using a dry gauze and forceps. Once 
hemostasis has occurred between 1 and 5 minutes later, the wound will be covered with a sterile 
dressing. The other wound will undergo primary closure. Both punch biopsy sites will be 
covered with a non-adherent dressing and a waterproof film dressing. 
 
The patient will be provided with a 2-week supply of NuvagenTM (collagen powder) in 1-gram 
containers and dressings along with instructions. Instructions will detail the following procedure: 
1) Irrigate the wound with tap water or saline solution, 2) Dry the wound with a dry gauze pad 
pat using gentle pressure, 3) Apply 1 gram of NuvagenTM (collagen powder) to the wound, and 4) 
Apply a sterile dressing which covers the entire wound. Assistance from a caregiver will be 
permitted in any instance in which this procedure is difficult for the patient to carry out for him 
or herself. This procedure is to be repeated daily for 2 weeks. On days of study visits, patients 
will be instructed to bring the day’s 1 gram of NuvagenTM (collagen powder) to the clinic for 
study coordinators to apply the corresponding day’s collagen treatment. 
 

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One week after wounding, the patient will return for visit 2. Patients will perform the Patient 
Overall Assessment Score, wounds will be measured, photographs will be taken, and inquiry will 
be made about any possible adverse events. The patient’s wound treated with collagen will then 
be treated and dressed in the office. 
 
One week after visit 2, the patient will return for visit 3. Sutures will be removed, and the wound 
treated with collagen will be evaluated for further collagen treatment. The principal investigator 
will determine if another 2 weeks of NuvagenTM (collagen powder) treatment will be warranted. 
If further collagen treatment is advised, the patient will be provided with another 2-week supply 
of NuvagenTM (collagen powder) and dressings. Patients will perform the Patient Overall 
Assessment Score, wounds will be measured, photographs will be taken, and inquiry will be 
made about any possible adverse events. The wound treated with collagen will be treated and 
dressed in the office. 
 
Two weeks after visit 3, the patient will return for visit 4. Both wound sites will be photographed 
and then biopsied again following the procedure from visit 1. Each wound will be treated 
identically (either with primary closure or with collagen powder) as it was in visit one. Patients 
will be provided with adequate supplies for at-home collagen treatment for 2 weeks. Patients will 
perform the Patient Overall Assessment Score, wounds will be measured, photographs will be 
taken, and inquiry will be made about any possible adverse events. 
 
Two weeks after visit 4, the patient will return for visit 5. Sutures will be removed, and the 
wound treated with NuvagenTM (collagen powder) will be evaluated for further collagen 
treatment. The principal investigator will determine if another 2 weeks of NuvagenTM (collagen 
powder) treatment will be warranted. If further collagen treatment is advised, the patient will be 
provided with another 2-week supply of NuvagenTM (collagen powder) and dressings. Patients 
will perform the Patient Overall Assessment Score, wounds will be measured, photographs will 
be taken, and inquiry will be made about any possible adverse events. The wound treated with 
collagen will be treated and dressed in the office. 
 
Six weeks after visit 5, the patient will return for visit 6. Patients will perform the Patient Overall 
Assessment Score, wounds will be measured, photographs will be taken, and inquiry will be 
made about any possible adverse events. 
 
3.5 Study Completion and Withdrawal Criteria 
 
It is the right and duty of the Investigator to discontinue the study participation of a subject when 
the subject's health or well-being is threatened by continuation in the study. Such subjects should 
be withdrawn from the study and not continued under a modified regimen. 
 
The following are circumstances that would result in the subject's discontinuation from the study: 
• 
The subject experiences a serious adverse event rendering them unable to continue study 
participation; 
• 
The subject is unable to physically or mentally tolerate the use of the lest medication; 
• 
An exclusion criterion becomes apparent at any time during the study, or the subject 
voluntarily withdraws. 

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In the event of premature discontinuation from the study, the Investigator should determine the 
primary reason for discontinuation. A subject who is withdrawn from the study prior to initiation 
of treatment may be replaced. 
 
3.6 Strength and Limitations of Proposed Research 
 
Strengths of the study include its relatively simple design and the potential for its completion 
within a short period of time due to the small number of participants (eight).  
 
Limitations of this study include the inability to conduct robust statistical analysis due to its 
small sample size.  However, the results of this project may lead to the development of larger 
studies that will have the statistical power to detect improvements.  
 
4. DATA VARIABLES, COLLECTION, AND EVALUATION 
4.1 Data Variables 
 
The following data will be evaluated in patients fulfilling inclusion and exclusion criteria and 
who agree to participate in the study. 
 
1. Sociodemographic Variables: Age, gender, and race. 
 
2.   Clinical History: 
a. Past medical history: All current and past medical conditions will be documented, 
allowing us to screen for the presence of any condition that, in the opinion of any of the 
investigators, would make the patient unsuitable for study inclusion. Allergies to 
medications will also be noted. 
b. Current medications: All medications will be recorded.   
c. Social History: We will screen for the presence of tobacco product use in addition to 
any drug or alcohol abuse within the past 6 months as determined by the medical record 
or patient interview. 
 
4.2 Wound specific variables 
 
Characterization of wound healing: Photographs of the wounds will be taken on week 0, 1, 2, 
and 4, at which time the areas will be re-sampled for histologic analysis, and then photographed 
again at the 4 week time point, followed by week 6 and then 12.  Photographs will be used to 
follow gross visual wound healing as assessed by the area of the wound uncovered by the 
migrating epithelia as measured digitally using ImageJ software. Digital measurements will be 
performed by 2 different members of the research team. 
Morphometric analysis of wound sections: Wound re-epithelialization will be measured in 
Hematoxylin and Eosin stained sections from the center of the wound. Dermatopathology 
procedures will be carried out by HistoWiz, Inc., Broolyn, NY. The distance between the wound 
edges, defined by the distance between the first hair follicle encountered at each end of the 
wound, and the distance that the epithelium had traversed into the wound, will be analyzed using 

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ImageJ. The percentage of re-epithelialization [(distance traversed by epithelium)/(distance 
between wound edges) x 100] will be calculated and averaged for 2 sections per wound. The 
quality of the epidermis and dermis will also be evaluated as a measure of wound maturation at 
the 4 week time point. 
Collagen deposition: Dermatopathology procedures will be carried out by HistoWiz, Inc., 
Broolyn, NY. Staining will be performed using Masson’s trichrome stain and the percentage of 
blue collagen-stained area relative to the total area of the wound bed after taking digital images. 
This will be quantified by counting the number of pixels staining above a threshold intensity and 
normalizing to the total number of pixels. 
Angiogenesis: Dermatopathology procedures will be carried out by HistoWiz, Inc., Broolyn, 
NY. Wound sections will be stained using CD31 antibody (also called platelet-derived 
endothelial cell adhesion molecule-1). Digital images at 40x magnification covering the majority 
of the wound bed will be taken. The percent area stained in each image will be quantified by 
counting the number of pixels staining above a threshold intensity and normalizing to the total 
number of pixels. Threshold intensity will be set such that only clearly stained pixels are 
counted. Staining identified as artifact, large vessels, and areas deemed to be outside the wound 
bed will be excluded. 
Patient Overall Assessment Scale. Patients will assess the overall improvement of their wounds 
using a 4-point scale, where 1 = excellent improvement, 2 = good / moderate improvement, 3 = 
no change, 4 = worsening. This assessment will be performed prior to every follow up visit after 
wounding at week 0, and upon study completion for each wound. Improvement will be indicated 
by a decrease by ≥ 1 point compared to the previous assessment. Worsening will be indicated by 
an increase in this scale by ≥ 1 point compared to the previous assessment. Patients will also be 
asked preference between the NuvagenTM (collagen powder) and primary closure. 
 
Pruritus Numerical Rating (NRS) Scale. Patients will also score pruritus on the validated NRS 
scale, which ranges from 1-10.  This assessment will be performed prior to every follow up visit 
after wounding at week 0, and upon study completion for each wound. Improvement will be 
indicated by a decrease by ≥ 2 points compared to the previous assessment. Worsening will be 
indicated by an increase in this scale by ≥ 2 points compared to the previous assessment. 
 
4.2 Data Collection 
 
All data variables will be stored in a secure database using coded identifiers in place of name.  
Most of the data will initially be recorded on approved study forms containing the participant's 
study ID code. After transfer of data into the computerized database, all paper forms will be kept 
in a secure locked cabinet within a locked office within the department.  Photographs will be 
stored with a secure electronic file and will be labeled with the participant's study ID code and 
date they were taken.  
 
4.3 Statistical Considerations 
 
Since this is a pilot study, we will perform only basic descriptive statistical analysis of our 
results.  Due to the small number of subjects, it is unlikely that any statistical test would have the 
power to detect a significant difference in any of the measured variables. Instead, we will look at 

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wound closure, quality of forming scar histologically, and assess patient experience and 
preference. The results of this project may lead to the development of larger studies that will 
have the statistical power to detect significant differences in these variables after treatment with 
NuvagenTM (collagen powder).  
 
5. HUMAN SUBJECTS PROTECTION 
 
5.1 Subject Selection 
 
At the time of recruitment, each potential subject will be provided with an informed consent 
form to read. The potential subject will be allowed to take the consent form home to discuss its 
content with family members or friends. All individuals will be given a contact number that they 
may call to obtain answers to any questions regarding the study and their participation.  All 
subjects must sign a consent form prior to any study procedures being performed. 
 
Involvement of special subjects such as pregnant women, institutionalized individuals, prisoners, 
or impaired and non-competent individuals are not anticipated in this study. Eligible women of 
reproductive age will be required to be on 1 reliable form of effective birth control during the 
treatment period. They will also be required to have a negative urine pregnancy test during the 
screening period and prior to each treatment session for the duration of the study. Individuals 
from all racial/ethnic groups, regardless of gender, and those that are economically and 
educationally disadvantaged are eligible for this study if they meet the eligibility requirements. 
 
5.2 Risks and Benefits 
 
Risks from punch biopsies include the possibility of pain, bleeding, itching, or infection at the 
biopsy site. Further, there is the possibility of persistent bruising, swelling, or scarring. Pain at 
the biopsy site will be minimized by use of a local anesthetizing agent. Excessive bleeding will 
be prevented by excluding patients with known coagulation disorders, patients taking aspirin, or 
patients taking anticoagulants (including heparin, low molecular weight heparin, warfarin, 
fondaparinux, or rivaroxaban). Further, bleeding will be minimized by applying adequate 
pressure using gauze on the biopsy sites. Previous work has shown that wound infections can 
occur in about 1 in every 6 outpatient skin biopsies.15 This study failed to subcategorize infection 
rate for each biopsy type, however, and included patients with medical co-morbidities which 
contribute to poor wound healing and development of infections. Risk of infection in our study 
will be minimized by excluding smokers, patients with diabetes mellitus, and patients with other 
medical or skin conditions that impair wound healing. Collagen is also a poor culture medium 
and can be left in wounds without risk of enhancing bacterial growth.14 
 
Patients may have an allergy or allergic reaction to the numbing agent used, but every attempt to 
prevent this will be made by asking the patient about his or her allergy history. Furthermore, 
there is a potential risk of allergy to the interventional type I NuvagenTM (collagen powder). 
Although studies have shown that it is possible to develop monoclonal antibodies to mammalian 
collagen, type I collagen has shown to be very poorly immunogenic.3,16,17 Nonetheless, there 
have been sparse reports of allergy to topical bovine-derived collagen.18 Minor amounts of non-
collagen proteins in collagen products have also been implicated in immunogenicity of collagen 

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products.19 Risk of allergy to the investigational agent used will be minimized further by 
excluding patients with history of known allergy or sensitivity to any component of the test 
medication (including bovine and/or collagen products). 
 
There is a potential risk of loss of privacy. All possible precautions will be taken to respect 
privacy and the confidentiality of patient information, and a secured database with coded 
identifiers will be used to keep privacy breach risk minimal. 
 
There is no guarantee of direct benefit from study involvement. Information from this study will 
be used to improve wound care practices after skin biopsies. Subjects could receive up to 
$590.00 total for participation if all study visits are attended. For each biopsy procedure, subjects 
will be compensated $125.00, for a total of $500.00 for all 4 planned biopsies obtained during 
the study (2 biopsies in visit 1, and 2 more biopsies in visit 4). In addition, subjects will be 
reimbursed $15.00 for travel expenses for each visit, for a total of $90.00 for all 6 planned study 
visits. Subjects will only receive payment for study visits attended and biopsy procedures already 
performed should he or she decide to stop the study early. Payments are to be made in full to the 
subject within 2 months after the final visit for the study. 
 
5.3 Confidentiality 
 
      All information collected as part of this study will be treated as confidential. Subject 
consent forms and data collection sheets will be stored in a locked office in the MFA 
Dermatology Department. These documents will be accessible to study investigators only. 
A computer database will be created. This database will not contain any subject identifiers. 
The data within the database will be labeled with each subject's study identification 
number. Database information will be maintained in a password-protected file. All the data 
included in this study will only be accessible to the investigators listed on the title page, 
and they will not be released for use by other researchers. 
 
5.4  Adverse Events and Safety Monitoring 
 
Patients will be closely monitored for any adverse events experienced during this study, as 
described in Section 5.2: Risks and Benefits. Adverse events monitoring will be performed by 
the principal investigator during each treatment session starting at visit 2. Any event occurring 
more than 8 weeks after the second pair of punch biopsies at visit 4 will not be considered an 
adverse event. Patients will be educated as to the possible side effects and complications related 
to punch biopsies and NuvagenTM (collagen powder), and will be instructed to notify any 
investigator should they experience signs or symptoms of an adverse event.  Because the 
anticipated risks associated with this study are low, we feel that an independent monitoring board 
will not be necessary. 
 
All events that meet the Prompt Reporting Requirements (HRP-801) (including but not limited to 
new or increased risk, harm experienced by the subject, noncompliance with the federal 
regulations governing human research, and state medical board actions) will be reported to the 
GW OHR via a Problem Report and Promptly Reportable Information Form (HRP-204) within 5 
business days of knowledge of the event.  

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Table 1: Example Study Schedule of Events* 
 
Week 
Screen*
* 
W0** 
W1 
W2 
W4 
W6 
W12 
Visit 
V1 
V1 
V2 
V3 
V4 
V5 
V6 
Informed Consent 
X 
 
 
 
 
 
 
Clinical History/ Screening 
Form 
X 
 
 
 
 
 
 
Wounding (punch biopsies) 
 
X 
 
 
X 
 
 
Wound measurements 
 
X 
X 
X 
X 
X 
X 
Patient Overall Assessment 
Scale 
 
 
X 
X 
X 
X 
X 
Pruritus Numerical Rating 
Scale 
 
 
X 
X 
X 
X 
X 
Photographs 
 
X*** 
X 
X 
X***
* 
X 
X 
Adverse Events 
 
 
X 
X 
X 
X 
X 
 
*Actual schedule and time between treatments may vary for each subject. **Screen and W0 procedures 
will take place in the same visit, V1. ***Photographs will be obtained immediately after the biopsy 
procedures. ****Photographs will be obtained immediately before and immediately after the biopsy 
procedures. 
 
 
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