Conditions: Acne Vulgaris
Keywords: skin of color acne skin diseases
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
Acne vulgaris is a common skin disease characterized by inflammatory papules, pustules, and comedones that is prevalent in men and women of color. Research has demonstrated that Aczone ® (dapsone) gel, 7.5% used once daily is effective, safe, and well-tolerated for the treatment of acne in both men and women; however, limited data is available regarding its efficacy and safety in skin of color (SOC). The current study aims to investigate the therapeutic impact of Aczone gel 7.5% in SOC males and females ages 18 and older with acne vulgaris. The study will also evaluate the impact of Aczone ® gel on hyperpigmentation and PIH of the face.

Detailed description:
Acne vulgaris is a common skin disease characterized by inflammatory papules, pustules, and comedones that is prevalent in men and women of color. In fact, acne is the most common dermatologic diagnosis made in SOC populations. Although individuals of all skin types can develop acne vulgaris, there are important differences in darker skin types that are important to consider when choosing an optimal treatment.

Complications from acne are of great concern in this population, as keloids, hypertrophic scars, and post-inflammatory hyperpigmentation (PIH) are more common in skin of color. PIH may last for weeks to months and, in many cases, is more troublesome to patients than the acne itself. Overall, facial acne and its sequelae have a greater impact on perception of appearance, negative emotions, and social functioning in women of color than white women.

Dapsone is a sulfone compound with anti-inflammatory properties that has been shown to be effective in the treatment of acne vulgaris in SOC. Aczone ® (dapsone) gel, 5% administered twice daily has been associated with significant improvement in overall acne severity, acne signs, and impact on quality of life in women of color. Two phase III trials of a newer formulation of Aczone ® (dapsone) gel, 7.5% used once daily demonstrated that this product is effective, safe, and well-tolerated for the treatment of acne in both men and women; however, limited data is available regarding its efficacy and safety in SOC.

Further, some investigators of the phase IV study on the safety and efficacy of dapsone gel 5% in SOC anecdotally reported improvement in hyperpigmentation over 12 weeks, although this was not a planned efficacy outcome. Further research is needed on the potential effects of dapsone gel on hyperpigmentation and PIH in SOC.

The current study will investigate the therapeutic impact of Aczone gel 7.5% in SOC males and females ages 18 and older with acne vulgaris. The study will also evaluate the impact of Aczone gel on post-inflammatory hyperpigmentation using the Postacne Hyperpigmentation Index (PAHPI) and mexameter-measured melanin index (MI).

Arms:
arm 1: Acne Vulgaris in Patients With Skin of Color

Interventions: intervention 1: Aczone Gel
Intervention descriptions: intervention 1: Aczone Gel 7.5%

Protocol document:
Prot_SAP_000.pdf: 
 
An Open-label Study to Investigate the Efficacy and Tolerability of Aczone Gel, 7.5% in the Treatment of 
Acne Vulgaris in Men and Women With Skin of Color   
Saakshi Khattri 
NCT03681470 
Document Date: Feb 7, 2022 
 


 
Protocol Document for 17-01277 
Principal Investigator: Saakshi Khattri, M.D. 
Mount Sinai  
 
Brief Summary of Research  
Acne vulgaris is a common skin disease characterized by inflammatory papules, pustules, and 
comedones that is prevalent in men and women of color. Research has demonstrated that Aczone 
® (dapsone) gel, 7.5% used once daily is effective, safe, and well-tolerated for the treatment of 
acne in both men and women; however, no data is available regarding its efficacy and safety in 
skin of color (SOC). The current study aims to investigate the therapeutic impact of Aczone gel 
7.5% in SOC males and females ages 18 and older with acne vulgaris. The study will also evaluate 
the impact of Aczone ® gel on hyperpigmentation and PIH of the face. 
 
Objectives 
The purpose of this study is to evaluate the safety and efficacy of Aczone ® gel, 7.5% administered once 
daily for 24 weeks in males or females with skin of color (SOC), defined as Fitzpatrick Skin Types IV, V, 
or VI, for the treatment of facial acne vulgaris. 
 
Background 
Acne vulgaris is a common skin disease characterized by inflammatory papules, pustules, and 
comedones that is prevalent in men and women of color. In fact, acne is the most common 
dermatologic diagnosis made in SOC populations (1). Although individuals of all skin types can 
develop acne vulgaris, there are important differences in darker skin types that are important to 
consider when choosing an optimal treatment (2). 
From a diagnosis standpoint, acne in women of color is more likely to present on the cheek area, 
as opposed to a chin and cheek predominance in white women (2). Complications from acne are of 
great concern in this population, as women of color are more likely to develop keloids, 
hypertrophic scars, and post-inflammatory hyperpigmentation (PIH) as a result of acne lesions (3). 
PIH may last for weeks to months and, in many cases, is more troublesome to patients than the 
acne itself (2). Overall, facial acne and its sequelae have a greater impact on perception of 
appearance, negative emotions, and social functioning in women of color than white women (2). 
Dapsone is a sulfone compound with anti-inflammatory properties that has been shown to be 
effective in the treatment of acne vulgaris in SOC (4). Aczone ® (dapsone) gel, 5% administered 
twice daily has been associated with significant improvement in overall acne severity, acne signs, 
and impact on quality of life in women of color (4). Two phase III trials of a newer formulation of 
Aczone ® (dapsone) gel, 7.5% used once daily demonstrated that this product is effective, safe, 
and well-tolerated for the treatment of acne in both men and women (5); however, no data is 
available regarding its efficacy and safety in SOC.  
Further, some investigators of the phase IV study on the safety and efficacy of dapsone gel 5% in 
SOC anecdotally reported improvement in hyperpigmentation over 12 weeks, although this was 
not a planned efficacy outcome (4). Further research is needed on the potential effects of dapsone 
gel on hyperpigmentation and PIH in SOC.  


 
The current study will investigate the therapeutic impact of Aczone gel 7.5% in SOC males and 
females ages 18 and older with acne vulgaris. The study will also evaluate the impact of Aczone 
gel on post-inflammatory hyperpigmentation using the Postacne Hyperpigmentation Index 
(PAHPI) and mexameter-measured melanin index (MI). 
 
 
Setting of the Human Research 
All research activity will take place at Mount Sinai Department of Dermatology. 
 
Resources Available to Conduct the Human Research 
 
The research team consists of the Principal Investigator, Sub-Investigator and Research Coordinator. We 
do not foresee any difficulties in recruiting the suggested number of patients for this research study. 
 
All members of the study team have several years of research experience and have all completed the 
required trainings and certifications mandated by our IRB.  
 
All research team members have read and understand the protocol and all study related procedures. 
 
 
Study Design 
 
a) Recruitment Methods 
 
Subjects will be recruited from the dermatology faculty practices and the dermatology 
resident clinics in the Mount Sinai Health System. Once approved by the Sponsor, we will 
use IRB approved flyers, online advertisements (including social media postings and 
clinical trials listing services) as well as questionnaires and phone scripts. 
 
b) Inclusion and Exclusion Criteria 
Inclusion: 
1. Provide written, signed and dated informed consent prior to initiating any study-related 
activities. 
2. Male or female subjects who are ≥ 18 years of age 
3. Subjects with Fitzpatrick Skin Type IV, V, or VI 
4. Subjects with moderate to severe acne as defined by investigator-assessed Global Acne 
Assessment Score (GAAS) of 3 or 4 at screening 
5. Facial acne vulgaris with 20 to 50 (inclusive) inflammatory lesions and 30 to 100 
(inclusive) noninflammatory lesion 
6. Stable non-progressive or regressive acne vulgaris in the investigator’s opinion 


 
7. Females of childbearing potential (FCBP) must have a negative pregnancy test at 
Screening and Baseline. A female is considered not to be of childbearing potential if 
she is post-menopausal with at least 12 consecutive months of amenorrhea or has 
undergone surgical sterilization. While on investigational product and for at least 28 
days after taking the last dose of investigational product, FCBP who engage in activity 
in which conception is possible must use one of the approved contraceptive options 
described below:  
Option 1:  Any one of the following highly effective methods:  hormonal 
contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine 
device (IUD); tubal ligation; or partner’s vasectomy; 
OR  
Option 2:  Male or female condom (latex condom or nonlatex condom NOT made 
out of natural [animal] membrane [for example, polyurethane]; PLUS one 
additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with 
spermicide; or (c) contraceptive sponge with spermicide. 
8. Must be in general good as judged by the Investigator 
9. Subject is willing to avoid excessive or prolonged exposure of the treated skin to ultraviolet 
light (i.e. sunlight, tanning beds) throughout the study 
10. Subject is willing to follow study instructions and complete study assessments without 
assistance and is likely to complete all required visits 
 
Exclusion: 
1. Diagnosis of other dermatologic diagnosis that, in the opinion of the investigator, 
would interfere with diagnosis, examination, or treatment of the studied condition 
(i.e. psoriasis, atopic dermatitis, lupus, dermatomyositis, seborrheic dermatitis, 
perioral dermatitis, etc.) 
2. Subjects with severe cystic acne, acne conglobate, acne fulminans, or secondary acne 
(chloracne or drug-induced acne) 
3. Uncontrolled systemic disease(s) that, in the opinion of the investigator, would put 
the patient at significant risk if enrolled in the study or would interfere with subject’s 
participation in the study 
4. Subjects with a history of clinically significant hemolysis, anemia, or enteritis 
(regional enteritis, ulcerative colitis, pseudomembranous colitis, antibiotic-associated 
colitis) 
5. Subjects with allergy or sensitivity to the study drug or its components 
6. Subjects who have not complied with the proper wash-out periods: 
a. Topical anti-inflammatory medications, salicylic acid, corticosteroids, 
antibiotics, antibacterials, peroxide-containing products, or retinoids within 2 
weeks of baseline 
b. Systemic antibiotics, corticosteroids, antimalarials or oral dapsone within 4 
weeks of baseline 


 
c. Other anti-acne medication, including isotretinoin or spironolactone, within 6 
months of baseline 
d. Chemical peels or other facial acne procedures (laser therapy, light therapy) 
within 3 months of baseline 
e. Treatment with botulinum toxin of any serotype in the face within 6 months of 
baseline 
f. Estrogens/Birth control pills must have been started ≥ 90 days prior to baseline 
and use must be continued during the study without alteration or 
discontinuation. 
7. Pregnant or breastfeeding.  
8. Subjects with evidence of alcohol or substance abuse. 
9. Use of any investigational drug within 4 weeks prior to randomization, or 
5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer). 
 
c) Number of Subjects 
Up to 40 subjects with acne vulgaris will be screened with a goal of 20 total subjects 
randomized. All 20 randomized subjects are expected to complete all study procedures. 
Individuals who provide informed consent and fail to meet all of the inclusion and 
exclusion criteria during the initial evaluation will be considered a “screening failure.” 
 
d) Study Timelines 
The study will consist of 6 in-person visits and one phone visit (7 total visits) over up to 28 
weeks (4 week screening period plus 24 weeks enrolled in study). Study visits will be 
conducted at Screening (Visit 1), Baseline (Visit 2, Week 0), Week 4 (Visit 3), Week 8 
phone visit (Visit 4), Week 12 (Visit 5), Week 18 (Visit 6), Week 24 (Visit 7). 
Enrollment will occur over a 24-36 month period from January 2018 to December 2020. 
The study is anticipated to be completed by December 2021. 
 
e) Endpoints 
 
Primary Endpoint:  
1. Mean change from baseline to week 12 in Global Acne Assessment Score (GAAS) 
 
Secondary Endpoints: 
1. Change from baseline in Global Acne Assessment Score (GAAS) at week 4, 18, and 24. 
2. Change from baseline in Post Acne Hyperpigmenation Index (PAHPI) at weeks 12, 18, and 
24. 
3. Change from baseline in Melanin Index (MI) of target lesion at weeks 12, 18, and 24 
4. Change from baseline in the proportion of subjects with score of 0 or 1 on ASIS “dark spot” 
score at weeks 4, 12, 18, and 24. 
5. Proportion of subjects with GAAS of 0 (none) or 1 (minimal) at weeks 4, 12, 18, and 24 


 
6. Percent change from baseline in all lesion counts (inflammatory, noninflammatory, and total) 
at weeks 4, 12, 18, and 24. 
 
 
f) Procedures Involved in the Human Research 
This is a single-center, single-group, open-label study using Aczone ® (dapsone) gel 7.5%. 
All subjects will receive the study medication. Aczone ® gel is an off-white to yellow gel 
with suspended particles. It is supplied in an airless pump containing a polypropylene 
bottle with a high density polyethylene piston. It will be dispensed as a 60g pump. 
Subject will apply Aczone ® once daily to the entire face. Study drug must not be applied 
to other areas of the body, including the upper chest, upper back or shoulders. 
Prior to the start of the study, potential subjects will be given an IRB-approved Informed Consent 
Document (ICD) containing a Health Insurance Portability and Accountability Act (HIPAA) 
disclosure agreement to read, understand, and sign. All questions about the study should be 
answered to the satisfaction of the candidate subject. They will have all of their study-related 
questions answered by the PI or designee, and if they agree to participate, the subject will sign two 
original copies of the ICD. The subjects will retain one original copy and one original copy will be 
kept in the study file. The subjects who sign an ICD will be assigned a screening number. 
 
After providing informed consent, subjects will be assessed for study eligibility at the Screening 
visit (day -28 to day -1), which includes review of medical history and concomitant, acne lesion 
counting and severity ratings, and serum pregnancy test (if applicable). The PI or a medically 
qualified designee must review this information (i.e. medical history, concomitant medication, and 
eligibility review) for each subject to confirm their eligibility before enrollment. A total of 20 
subjects who meet eligibility criteria will undergo Baseline / Day 0 assessments. Subjects will 
return for visits at weeks 4, 12, 18, and 24. There will be a phone visit at week 8.  
 
Study Assessments and Efficacy Measures: 
 
Global Acne Assessment Score (GAAS): 
The subject’s acne severity will be assessed by the investigator using a 5-point GAAS at screening, 
baseline, and weeks 4, 12, 18, 24. 
 
Grade 
Description 
0 
None 
No evidence of facial acne vulgaris 
1 
Minimal 
Few noninflammatory lesions are present; a few inflammatory lesions 
(papules/pustules) may be present; no nodulo-cystic lesions present 
2 
Mild 
Several to many noninflammatory lesions are present; a few inflammatory 
lesions are present; no nodulo-cystic lesions present. 
3 
Moderate 
Many noninflammatory and inflammatory lesions are present; no nodulo-
cystic lesions are present. 
4 
Severe 
Significant degree of inflammatory disease; papules and pustules are a 
predominant feature; a few nodulo-cystic lesions are present (no more than 2) 
 
 
 
Lesion Counts: 
The lesion counts, including inflammatory and non-inflammatory lesions, will be performed at screening, 
baseline, and weeks 4, 12, 18, and 24. Inflammatory lesions (papules, pustules, nodules/cysts) and 


 
noninflammatory lesions (open comedone, closed comedone) will be counted individually. The sum of the 
inflammatory lesion counts and non-inflammatory lesion counts will be totaled. 
 
ASIS ®: 
Acne Symptom and Impact Scale (ASIS ®) will be given to subjects’ for completion at baseline and weeks 
4, 12, 18, and 24. The ASIS ® contains 9 items assessing symptom severity and 8 items assessing the 
psychosocial impact of acne vulgaris (6). High scores on the ASIS® indicate the presence of more severe 
symptoms, whereas higher scores on the ASIS indicate better outcomes on acne health-related quality of 
life. 
 
PAPHI: 
The postacne hyperpigmentation index (PAHPI) has been shown to be a reliable and valid score measuring 
post-inflammatory hyperpigmentation from acne (7). PAHPI will be scored using the following formula: 
 
Total PAHPI = S + I + N 
PAHPI Score can range from 6-22. 
 
 
Lesion Size (S) 
Weighted 
Score (S) 
Median 
Lesion size 
2 
<3mm 
4 
3-6mm 
6 
7-10mm 
8 
>10mm 
 
Lesion Intensity (I) 
Weighted 
Score (I) 
Median Lesion Intensity 
3 
Slightly darker than surrounding 
skin 
6 
Moderately darker than 
surrounding skin 
9 
Significantly darker than 
surrounding skin 
 
  
Lesion Number (N) 
Weighted 
Score (N) 
Number of 
Lesions 
1 
1-15 
2 
16-30 
3 
31-45 
4 
46-60 
5 
>60 


 
Melanin Index: 
A narrowband reflectance spectrophotometer (mexameter MX-16) will be used to measure the 
degree of pigmentation of involved and adjacent uninvolved skin of one representation facial PIH 
lesion (8). 
The mexameter contains 16 light emitting diodes arranged circularly that emit light at 
wavelengths of 568nm (green), 660nm (red), and 880nm (near infrared). The machine then 
measures the amount of light absorbed and reflected by the skin to measure the melanin content 
(melanin index or “M” – red and near infrared light) and hemoglobin content (erythema index or 
“E” – green and right light).  
One target lesion will be chosen by the investigator, which will be the darkest spot involved by 
post-inflammatory hyperpigmentation without evidence of active acne lesion (inflammatory or 
non-inflammatory lesion). The target lesion must be on the face and easily accessible with the 
mexameter probe. The probe will be applied to the target lesion on the skin with light, constant 
pressure. Both the “M” and “E” indices will be recorded. The location of the target site will be 
recorded using distance from anatomic landmarks. 
 
Skin Phototype Assessment: 
At screening, Fitzpatrick skin type (FST) will be rated by the investigator: 
I: always burns, never tans (very pale) 
II: always burns, tans minimally (pale) 
III: burns moderately, tans gradually (light brown) 
IV: burns minimally, always tans well (moderate brown) 
V: rarely burns, tans profusely (dark brown) 
VI: never burns, deeply pigmented (very dark brown) 
 
Photography: 
Standardized photographs will be taken by study personnel at baseline and weeks 12, 18, and 24 
using standardized cameras and photographic equipment.  
 
Subject Safety Measures: 
The following safety measures will be collected: 
- 
Adverse events 
o The investigator will question the subject at all scheduled visits and one phone visit 
to determine whether adverse events were experienced since the prior visit. The 
adverse event and all applicable information (date of onset, date of stop, duration, 
outcome, severity, relationship to study drug, action or treatment required) will be 
obtained and recorded on the source documents and adverse event CRF. 
- 
Local tolerability assessments  
o Investigator will ask subject to rate subjective burning/stinging using the following 
scale: 0 = absent (normal, no discomfort), 1 = trace (an awareness, but no discomfort 
and no intervention required), 2 = mild (noticeable discomfort causing intermittent 
awareness), 3 = moderate (noticeable discomfort causing continuous awareness),  4= 
marked (definite discomfort causing continuous awareness, interfering occasionally 
with normal daily activities), 5 = severe (definite, continuous discomfort interfering 
with normal daily activities) 
o Investigator will rate erythema, dryness, peeling, and oiliness using the following 
scale: 
 
 
Score 
Erythema 
Dryness 
Peeling 
Oiliness 
0=absent 
No redness 
None 
Smooth 
Normal 


 
1=trace 
Faint red or pink 
coloration, barely 
perceptible 
Barely perceptible dryness by 
palpation with no accentuation 
of skin markings, skin 
desquamation (flakes) or fissure 
formation 
Fine peeling, 
barely perceptible 
Mild and localized 
2=mild 
Light red or pink 
coloration 
Easily perceptible dryness by 
palpation with accentuation of 
skin markings but no skin 
desquamation (flakes) or fissure 
formation 
Slight peeling 
Mild and diffuse 
3=moderate 
Medium red 
coloration 
Easily noted dryness with 
accentuation of skin markings 
and skin desquamation (small 
flakes) but no fissure formation 
Definitely 
noticeable peeling 
Moderate and diffuse 
4=severe 
Beet red 
coloration 
Easily noted dryness with 
accentuation of skin marking, 
desquamation (large flakes) 
and/or fissure formation 
Extensive peeling 
Prominent and dense 
 
- 
Urine pregnancy tests at screening, baseline, and weeks 4, 12, 18, and 24. 
- 
Concomitant medications and procedures 
 
Drug Dispensation: 
 
Drug will be dispensed at the baseline visit and the first dose of study drug will occur during this 
visit in the office under the investigator’s supervision. The subject will gently wash the face and 
pat it dry. Then the subject will apply a pea-sized amount in a thin layer to the entire face and rub 
in the product gently and completely until there is no visible mass of gel observed on the face. All 
subjects will be provided a subject application instruction sheet. Adherence to the instructions 
will be assessed at subsequent visits and subjects will be re-trained at scheduled visits if 
necessary. Additional study drug will be dispensed every 4-8 weeks as needed. 
 
 
Visit Schedule: 
Screening: 
 
- 
Informed Consent 
- 
Demographics 
- 
Inclusion/Exclusion 
- 
Medical History 
- 
Concomitant medications and procedures 
- 
Skin phototype assessment (Fitzpatrick Skin Type) 
- 
Lesion Counting 
- 
Global Acne Assessment Score (GAAS) 
- 
Adverse events 
- 
Urine pregnancy 
 
Baseline 
- 
Inclusion/Exclusion 
- 
Adverse events 
- 
Concomitant medications and procedures 
- 
Lesion Counting 
- 
Melanin index 


 
- 
GAAS 
- 
Post Acne Hyperpigmentation Index (PAHPI) 
- 
ASIS dark spot score 
- 
Local tolerability assessment 
- 
Photography 
- 
Urine pregnancy 
- 
Product dispensation/return 
 
Week 4 – 
- 
Adverse events 
- 
Concomitant medications and procedures 
- 
Lesion Count 
- 
GAAS 
- 
ASIS dark spot score 
- 
Local tolerability assessment 
- 
Pregnancy test 
- 
Product dispensation/return 
Week 8 Phone Visit –  
- 
Adverse events 
- 
Concomitant medications and procedures 
Week 12 –  
- 
Adverse events 
- 
Concomitant medications and procedures 
- 
Lesion Counting 
- 
GAAS 
- 
PAHPI 
- 
ASIS dark spot score  
- 
MI  
- 
Photography  
- 
Local tolerability assessment 
- 
Product dispensation/return  
- 
Urine pregnancy test 
Week 18 – 
- 
Adverse events 
- 
Concomitant medications and procedures 
- 
Lesion Counting 
- 
GAAS 
- 
PAHPI 
- 
ASIS dark spot score  
- 
MI  
- 
Photography  
- 
Local tolerability assessment 
- 
Product dispensation/return  
- 
Urine Pregnancy test 


 
Week 24 –  
- 
Adverse events 
- 
Concomitant medications and procedures 
- 
Lesion Counting 
- 
GAAS 
- 
PAHPI 
- 
ASIS dark spot score  
- 
MI  
- 
Photography  
- 
Local tolerability assessment 
- 
Product return  
- 
Urine Pregnancy test 
 
 
Table 1: Assessment Schedule 
 
 
 
 
Visit 1 
2 
3 
4 
5 
6 
7 
Week -4 to BL 
 
0 (BL) 
4 
8 
phone 
12 
18 
24 
Visit Window (days)  
 
±3 
±3 
±3 
±3 
±3 
Assessment 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Fitzpatrick Skin Type 
X 
 
 
 
 
 
 
AE/SAE assessment 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Concomitant procedures 
X 
X 
X 
X 
X 
X 
X 
Photography 
 
X 
 
 
X 
X 
X 
Urine Pregnancy Test 
X 
X 
X 
 
X 
X 
X 
Lesion Count 
X 
X 
X 
 
X 
X 
X 
GAAS 
X 
X 
X 
 
X 
X 
X 
ASIS ® 
 
X 
X 
 
X 
X 
X 
PAHPI 
 
X 
 
 
X 
X 
X 
Mexameter – Melanin Index 
 
X 
 
 
X 
X 
X 
Local tolerability  
 
X 
X 
 
X 
X 
X 
Study Drug Dispensation and 
Return 
 
X 
X 
 
X 
X 
X 


 
g) Specimen Banking 
Not applicable. 
 
h) Data Management and Confidentiality 
 
As used in this protocol, the term case report form (CRF) should be understood to refer to 
either a paper form or an electronic data record or both, depending on the data collection 
method used in this trial. All subject source documents are the site’s subject records and 
are to be maintained at the study site. These source documents must be attributable, 
legible, contemporaneous, original, and accurate.  
 
A CRF/source document is required and should be completed for each included subject. 
It is the PI's responsibility to ensure completion and to review and approve all 
CRFs/source documents. These must be signed by the PI or by an authorized staff 
member. These signatures serve to attest that the information contained on the 
CRFs/source documents is true. At all times, the PI has final personal responsibility for 
the accuracy and authenticity of all clinical and laboratory data entered on the 
CRFs/source documents.  SAE forms and pregnancy notification forms will be provided 
by the Sponsor.  
 
Good documentation practices should be used on all study documentation. The clinical 
study will be performed in accordance with the protocol, applicable standard operating 
procedures (SOPs), the International Conference on Harmonization Good Clinical 
Practice (ICH GCP) guidelines, and applicable local regulatory requirements and laws. 
 
The Sponsor requires that all records (e.g., ICFs, documents, test article dispensing record, 
etc.) which support CRFs/source documentation of this study must be retained in the files 
of the responsible investigator for a period of 2 years from the time the final report is issued. 
If the investigator relocates, retires, or for any reason withdraws from the trial, the Sponsor 
should be prospectively notified. The study records must be transferred to an acceptable 
designee, such as another investigator, another institution, or to the Sponsor.  The 
investigator must obtain Sponsor's written permission before disposing of any records, 
even if retention requirements have been met.  The Sponsor must be notified in writing of 
the name and address of the new custodian prior to re-assignment/transfer. 
All records identifying the subject will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly 
available. Only the subject number will be recorded in the CRF. The code that 
links the subject to the subject’s ID# is stored on paper in a locked cabinet, 
accessible only by Department of Dermatology research personnel. Photographs 
will be stored on the camera for approximately one week before being transferred 
to the computer database. Study findings stored on a password- protected 
computer will be encrypted and stored in accordance with local data protection 
laws. As part of the informed consent process, the subjects will be informed in 


 
writing that representatives of the IRB, or regulatory authorities may inspect their 
medical records to verify the information collected, and that all personal 
information made available for inspection will be handled in strictest confidence 
and in accordance with local data protection laws. If the results of the study are 
published, the subject’s identity will remain confidential. Only the investigator 
will maintain a list to enable subjects to be identified. The data will be stored 
indefinitely.  
 
i) Provisions to Monitor the Data to Ensure the Safety of Subjects 
 
Part I: Elements of a Data and Safety Monitoring Plan 
 
MSSM Principal Monitor: 
Indicate whether this person is the PI, a Team Member, or is Independent: 
Last Name: Khattri (PI) 
First Name: Saakshi 
Academic Title: MD 
Department: Dermatology 
Mailing Address: 
 
 
, New York, NY 10023 
Phone: 212-523-3812 
Fax: 212-523-6293 
E-mail: Saakshi.khattr@mountsinai.org 
 
MSSM Additional Monitor: 
Indicate whether this person is the PI, a Team Member, or is Independent: 
Last Name: Sanabria-Gonzalez (Team Member) 
First Name: Ingrid 
Academic Title: Research Manager 
Department: Dermatology 
Mailing Address: 
 
 
, New York, NY 10023 
Phone: 212-523-3812 
Fax: 212-523-6293 
E-mail: Ingrid.sanabria@mountsinai.org 
 
3. The principal monitor is the Principal Investigator. Please refer to curriculum vitae for 
further information. 
4.  The specific items that will be monitored for safety are adverse events, subject 
compliance with the protocol and withdrawals. Subjects will be monitored for adverse 
events the day of their participation in the study. Should subjects experience any 
adverse effects after their participation in the study, they will be instructed to contact 
the investigator(s) and make an appointment immediately.  
5. Accumulated safety and data information will be reviewed annually. 
6. N/A  
7. N/A 


 
8.  Adverse events will be graded using the Common Terminology Criteria for Adverse 
Events (CTCAE).    
9. The study will be conducted in compliance with regulatory requirements and Good 
Clinical Practice. Quality control will be applied to each stage of data handling to 
ensure that data are accurate, reliable and processed correctly.  
10.  Should a temporary or permanent suspension of our study occur, the occurrence will 
be reported to the PPHS, sponsor, and IRB.  
 
 
Part II. Data Monitoring Committee/Data Safety Monitoring Board (DMC/DSMB) 
 
 
Not applicable 
 
j) Withdrawal of Subjects 
When an individual who has signed the ICF is not enrolled in the study or withdraws/is 
withdrawn prior to completing the study, the reason is to be documented on the 
Discontinuation/Completion Form (or equivalent) and in the final study report.  Reasons 
for subject withdrawal may include:  
 Not enrolled (e.g. fails to meet inclusion/exclusion criteria, chooses not to enroll, etc.) 
 Participant is determined to be ineligible after enrollment 
 Subject’s choice to withdraw 
 Investigator terminated (e.g. noncompliance, etc.) 
 Adverse Event 
 Pregnancy 
 Lost to follow-up 
 Other 
 
Subjects may withdraw from the trial at any time at their request, or they may be withdrawn 
at any time at the discretion of the Sponsor, PI, or designee for safety, behavioral, or 
administrative reasons. Subjects may be withdrawn from this study without their consent 
if the research study is being stopped; or if the instructions of the study team have not been 
followed. 
 If a subject does not return for a scheduled visit, three documented attempts will be made 
to contact the subject in order to establish the reason for withdrawal, and the outcome 
will be documented.  The PI or designee should inquire about the reason for withdrawal, 
request that the subject return for a final visit, if applicable, and follow-up with the 
subject regarding any unresolved adverse events.   
 
Should a subject withdraw from the trial and also withdraw consent for disclosure of 
future information, no further evaluations should be performed and no additional data 
should be collected.  The PI and staff may retain and continue to use any data collected 
before such withdrawal of consent.  Removed or withdrawn subjects will not be replaced. 
 


 
If a subject fails to report to the test facility for a scheduled visit and cannot be 
rescheduled within the permitted window of time (as applicable), the Site should consult 
with the Sponsor to determine if the subject should be documented as having 
withdrawn/dropped from the study. 
 
Risks to Subjects 
 
The following list of side effects is the ones that may be associated with the use of dapsone gel: 
 
 
Common: 
 Application site reactions: 
o Dryness 
o Peeling 
o Oiliness 
o Erythema 
o Pruritus 
 Temporary yellow or orange discoloration of treated skin and local facial hair 
(when used in conjunction with benzoyl peroxide) 
 
Rare: 
 Methemoglobinemia – Cases of methemoglobinemia have been reported post-
marketing in subjects using dapsone 5% gel twice daily. Initial signs and 
symptoms include slate grey cyanosis, which may be observed on the buccal 
mucous membranes, lips, and nail beds.  Increased susceptibility to 
methemoglobinemia is seen patients with glucose-6-phosphate (G6PD) 
deficiency. The risk is also elevated in individuals taking other medications that 
induce the formation of methemoglobin (i.e. sulfonamides, acetaminophen, 
acetanilide, aniline dyes, benzocaine, chloroquine, naphthalene, nitrates and 
nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-
aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine). 
Dapsone gel should be avoided in patients with known history of congenital or 
idiopathic methemoglobinemia. Patients should be instructed to discontinue use of 
dapsone gel immediately and seek medical attention if they develop any signs of 
cyanosis.  
 Hemolysis – The use of oral dapsone has been associated with the development of 
hemolysis and hemolytic anemia, particularly in patients with G6PD deficiency. 
G6PD deficiency is most common in individuals of Mediterranean, African, 
South Asian, and Middle Eastern descent. Studies and post-marketing on dapsone 
gel has not demonstrated any clinically relevant hemolysis of hemolytic anemia in 
treated subjects. Lab changes suggestive of hemolysis have been seen in patients 
with G6PD deficiency using dapsone gel 5%. Dapsone gel should be used with 
caution in patients taking oral medications known to increase serum levels of 
dapsone, including trimethoprim/sulfamethoxazole, and should be avoided in 
patients taking oral dapsone and anti-malarial medications due to risk of 
hemolytic reactions. 


 
 Peripheral neuropathy – peripheral neuropathy has been observed with use of oral 
dapsone. No cases have been reported in patients using dapsone gel. 
 Significant skin reactions (toxic epidermal necrolysis, erythema multiforme, 
morbilliform and scarlitiniform reactions, bullous and exfoliative dermatitis, 
erythema nodosum, urticarial) – With the exception of urticaria, no significant 
skin reactions have been observed during clinical trials and post-marketing with 
use of dapsone gel.  
 
 
 
Aczone gel is designated as pregnancy category C, meaning that there are no adequate and 
well controlled studies in pregnant women. Dapsone administered orally in rats and rabbits 
has demonstrated embryocidal effects during the period of organogenesis when dosed at 425 
to 1400 times the maximum recommended human dose (MRHD). 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age 
or disease state) of a female subject or the female partner of a male subject occurring while 
the subject is on study drug, or within 30 days of the subject’s last dose of study drug, are 
considered immediately reportable events.  Study drug is to be discontinued immediately and 
the subject instructed to return any unused portion of the study drug to the investigator(s).  
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Allergan 
Safety immediately facsimile using the Pregnancy Report form provided by the company. 
The female should be referred to an obstetrician-gynecologist experienced in reproductive 
toxicity for further evaluation and counseling. The Investigator(s) will follow the female 
subject until completion of the pregnancy, and must notify Allergan Safety of the outcome of 
the pregnancy as a follow-up on the follow up Pregnancy Reporting form. 
 
 
Provisions for Research Related Harm/Injury 
 
If a subject experiences a research injury, Mount Sinai West will provide or arrange for medical 
treatment at no cost. If the subject chooses to see their own personal doctor we will not offer to 
pay for the expenses. A research injury is any physical injury or illness caused by participation in 
the study. If a subject is injured by a medical treatment or procedure that would have been 
received even if the subject weren't in the study; that is not a research injury.  Payment for things 
such as lost wages, expenses other than medical care, or pain and suffering is not offered. To 
help avoid injury, it is very important to follow all study directions. 
 
Please be aware that some insurance plans may not pay for research-related injuries.  Subjects 
should contact their insurance company for more information. 
 
Unreimbursed medical expenses not covered by insurance or other third party coverage will be 
reimbursed by the sponsor for medical treatment for any injury that, in the opinion of the study 
doctor and the sponsor, is directly caused by the study drug/investigational product or by 
procedures required by the study protocol which would not have been performed as part of 
regular medical care. 
 


 
Provisions to Protect the Privacy Interests of Subjects 
Only subjects who have given us permission to contact them for studies will be 
contacted. All conversations with subjects and potential subjects will be conducted in a 
private examination room with the subject. Subjects’ privacy will be protected by 
performing any study-related procedures in a private examination room. Family members 
will be allowed to remain in the room only if the subject allows this. No information 
regarding the subject’s disease, treatment or the fact that he/she is involved in a study will 
be conveyed. Subjects will be made to feel at ease, by allowing them sufficient time to 
discuss the study and any potential queries. 
All parties will ensure protection of subject personal data and will not include subject names on 
any Sponsor forms, reports, publications, or in any other disclosures. In case of data transfer, 
Sponsor will maintain high standards of confidentiality and protection of subject personal data.   
The ICF (containing the HIPAA disclosure agreement) must be agreed to by Sponsor and the IRB 
and be in compliance and consistent with ICH GCP, local regulatory requirements, and legal 
requirements. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the trial, possible risks associated with participation. The investigator, or a trained 
person designated by the investigator, will obtain written informed consent on two copies from 
each subject before any trial-specific activity is performed.  The subject will retain one copy, and 
one will be kept in the study file. The ICF used in this trial, and any changes made during the 
course of the trial, must be prospectively approved by both the IRB and Sponsor before use.  
 
Economic Impact on Subjects 
Allergan, the manufacturer of the study drug, will provide the study drug. Allergan also covers 
the cost of all study-related tests and procedures. While in the study, the subject will still need to 
get regular medical care. The subject will still have to pay for the costs of regular medical care 
that is not a part of this study. 
 
Taking part in this research study may lead to added costs to the subject. If the laboratory tests or 
physical examinations reveal information about his/her health, additional tests, treatments and 
doctors appointments may be required which could present additional costs to him/her or his/her 
insurance company. 
 
Payments to Subjects 
Subjects will be compensated $25.00 per completed in-person visit for a total of $150.00 
upon completion of the study. Subjects will not be compensated for the week 8 phone 
visit. Subjects who complete only the screening visit will not be eligible for 
compensation. If the subject withdraws or is withdrawn before completing the study, 
he/she will receive an amount of money for the visits which have been completed.  They 
will not have to submit receipts to receive this reimbursement. This payment will come in 
the form of a check at the end of the subject’s participation in the study.  


 
Consent Process 
We will be obtaining written consent as a part of this study. No subject will be evaluated without 
a signed Informed Consent Form (ICF).  
 
The consent process will take place in a private exam room where the subject will have ample 
time to review and read the consent form. Subjects will be given time to ask questions and may 
take additional time to consider their options. Subjects will be informed that they do not have to 
participate and may withdraw consent at any time.  
 
After understanding and agreeing, the subject will express their consent to participate in the 
study by signing an original copy of the ICF. The subject will receive a copy of their signed 
document for their records. 
 
We will follow the SOP HRP-090 Informed Consent Process for Research. 
 
Process to Document Consent in Writing 
We will be using the standard IRB Informed Consent template. The ICF must be agreed 
to by the Sponsor and the IRB and must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements.  
The consent process and date that the consent is signed is documented in our source 
notes.  
Study personnel will adhere to “SOP HRP-091 Written Documentation of Consent”. 
 
Vulnerable Populations 
 
 This project will not include any vulnerable population subjects. 
 
 
Multi-Site Human Research (Coordinating Center) 
 
 This project is a single site study. 
 
Community-Based Participatory Research 
 
  This project will not involve any community-based participation. 
 
Sharing of Results with Subjects 
 
At the completion of the study, subjects will have the right to access their protected health 
information that is created during this research study that relates to their treatment or to payment, 


 
provided such information is not exempted under certain laws and regulations.  To request this 
information, subjects should contact the study doctor at the address listed above. 
 
Subject to certain exceptions prescribed by law, subjects have a right to request access to the health 
information that we hold about and to request changes if the health information is incorrect or 
incomplete. Any request for access or corrections should be made to the principal doctor 
conducting this study. 
 
Once all data and results are finalized, a summary will be made available to subjects. 
 
External IRB Review History 
This project is not using an external IRB. 
 
Control of Drugs, Biologics, or Devices 
 
Study drug is stored in a combination-locked room accessible only by clinical trials personnel. All 
study materials should be stored at room temperature (59°-77°F), and the Site is responsible for 
maintaining temperature logs. All study products received and dispensed will be inventoried and 
accounted for throughout the study. The investigator must maintain adequate records documenting 
the receipt, use, loss, or other disposition of the products on the Product Accountability Log. The 
log must identify the investigational product and account for its disposition by subject, including 
specific dates and quantities dispensed and returned. The log must be signed by the individual who 
dispensed/retrieved the study product and copies must be provided to the sponsor for inclusion in 
the Trial Master File. 
 
At the completion of the study, all units of product dispensed (whether empty or containing unused 
product) must be collected by the Site and returned, along with un-dispensed product, to the 
Sponsor.  Any container not returned by the Site must be accounted for in writing.    
 
 
 
k) Statistical Analysis Plan 
 
The adverse events will be tabulated according to their date of onset, duration, severity and 
relationship to the treatment. We will build Clopper-Pearson 90% confidence intervals for the 
proportion of adverse events considering their aggregation and stratification (e.g., by severity).  
 
Sample Size Considerations 


 
A sample size of n=20 subjects allows >90% power at 5% significance level for a two-sided paired 
t-test to detect at week 12 a minimum change in GAAS from baseline of 1 grade point. This 
calculation was performed in G*Power and it assumes a mean GAAS of 3.5 at baseline and a 
maximal standard deviation of 0.513.  
 
Analysis of primary Endpoint 
The primary analysis will apply a two-sided paired t-test to assess the significance of the change 
in GAAS from baseline to week 12. However, GAAS is an ordinal measurement and, for this 
reason, we will also apply a Generalized Linear Mixed-effects Model (GLMM) to assess the 
significance of the changes in GAAS after including potential covariates.  
Analysis of secondary Endpoints 
At each time point, the changes from baseline in ordinal secondary endpoints GAAS, PAHPI, 
MI, the proportion of subjects with a score of 0 or 1 on ASIS “dark spot,” the proportion of 
subjects with GAAS <2 will be presented in frequency tables. The (i,j) entries in the tables are 
counts of subjects in category i at baseline that moved to category j at that time point. A high 
frequency of counts falling off the main diagonal of the table is evidence in favor of a significant 
treatment effect. Similarly, to the primary endpoint, we will apply a two-sided paired t-test to 
assess the significance of changes from baseline in each outcome. We will apply the Bonferroni 
correction to adjust for the multiplicity of tests. In parallel, we will test pre vs. post differences in 
these ordinal outcomes with the Wilcoxon Signed Rank test. Discrepancies between the 
parametric and non-parametric approaches will be discussed on a case basis.  In addition to this 
approach, we will fit an ordinal logit model, including all available time points, age, and gender 
as covariates.  
The changes from baseline in lesion counts (inflammatory, non-inflammatory, and their 
aggregation) will be assessed with the two-sided paired t-test followed by Bonferroni correction. 
A Generalized Linear Mixed Model (GLMM) will be fitted to model the count of lesions as the 
dependent variable, time and inflammation as fixed effects, age, and gender as covariates. In this 
framework, we will include random intercept and slope for each subject’s trajectory. The 
contrasts will reveal differences between time points and treatment effect in inflammatory vs. 
non-inflammatory lesions.  
Missing Data and Outliers 
Missing data in the longitudinal data analysis will be handled by the mixed-effects approach 
which performs an appropriate adjustment of the coefficients’ degrees of freedom for each fitted 
model. We do not foresee issues with outliers due to the endpoints’ measurement level, most of 
them being ordinal.  
 
 


 
 
 
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