Efficacy and Safety of Duobrii in the Management of Acne Keloidalis Nuchae (AKN)
Phase: PHASE3
Conditions: Acne Keloidalis Nuchae, AKN
Sponsor: Icahn School of Medicine at Mount Sinai

Efficacy and Safety of Duobrii in the Management of Acne Keloidalis Nuchae (AKN) 
PI: Emma Guttman-Yassky, MD, Ph.D
NCT05608499
Document Date: 8/1/2023

1
Title: 
Efficacy and safety of Duobrii in the management of 
Acne Keloidalis Nuchae (AKN)
Principal Investigator:
Emma Guttman-Yassky, MD, Ph.D
Investigators:
Marguerite Meariman, MD
Mark Taliercio, MD
Anusha Pasumarthi, MD
Study Site:
Icahn School of Medicine at Mount Sinai
Department of Dermatology 
5 East 98th Street - 5th Floor, Box 1048
New York, NY 10029
Tel:  212-241-3288
Protocol Version Date: 
August 15, 2022
Amendment #1 Version:
03 October 2022
Amendment #2 Version:
26 October 2022
Effective Date: 8/1/2023
End Date:7/31/2024

2
INTRODUCTION:
Acne keloidalis nuchae (AKN) is one of the chronic forms of scarring folliculitis, affecting 
predominantly the occipital scalp, seen mostly in men of African descent. It has been 
reported in a few Caucasians and other ethnic groups. The reported prevalence in African 
Americans ranges from 0.5% to 13.6%1. The pathogenesis is yet to be elucidated. 
However, inflammation is central to its pathogenesis. Standard dermatologic 
recommendations for early or mild disease with non keloidal lesions include potent topical 
steroids which may be combined with topical retinoids. Early to mild disease, for the 
purpose of this study, includes class I and Class II AKN as defined by Lullo et al.2 
Combining a topical corticosteroid with a topical retinoid allows for dual mechanistic action 
in the management of AKN; the topical corticosteroid, provides a primarily anti-
inflammatory effect and the vitamin A derivative, impairs keratinocyte proliferation. Duobrii 
has the advantage of being the only high potency topical steroid-retinoid combination 
approved by the FDA with dermatologic indication. We are, thus, proposing, the off-
labeled use, of Duobrii for the management of early-mild AKN.
HYPOTHESIS:
Primary Hypothesis:
1. Subjects treated with Duobrii will experience significant clinical improvement in 
lesion counts, symptoms associated with AKN as well as minimal dyspigmentation 
when compared to patients receiving placebo.
STUDY OBJECTIVE
Evaluate the efficacy and safety of Duobrii in the management of early to mild AKN
ENDPOINTS:
Primary Endpoint

The primary endpoint will be clinical improvement as assessed by lesion counts 
and captured by photography.
Secondary Endpoint

Patient reported outcome, improvement in severity of AKN associated symptoms 
as well as degree of dyspigmentation.
STUDY DESIGN OVERVIEW:
Following IRB approval, we will conduct a single center, prospective, double-blinded 
placebo vs. active-control trial assessing the efficacy of the vehicle vs. Duobrii, 
respectively, in the management of AKN over 3 months.
Effective Date: 8/1/2023
End Date:7/31/2024

3
Blinding will be performed by pharmacy and research staff. In addition, different 
investigators will do the clinical enrollment and follow up vs. statistical analysis.
Patients with class I and class II AKN (Appendix C) from our various clinics at our Skin of 
Color Center will be screened with plan to enroll 30 participants after obtaining written 
informed consent. In addition, flyer announcement of our trial will be distributed and active 
patient recruitment will be conducted at various local barber shops and social media 
platforms (instagram, twitter and facebook) to increase patient recruitment. 
Enrolled participants will be instructed to apply placebo (n=10) vs. active (n=20) to 
affected area of the occipital scalp for 4 weeks once a day (label use). Each application 
will be approximately 1g. Following the 4 weeks, participants will be instructed to increase 
application to twice daily (BID; off-label; at least 8 hours apart) for one week. Investigators 
will conduct a phone visit on week 5 to discuss any potential side effects with this 
increased dose. If tolerated, this BID regimen will be carried throughout the length of the 
study. If BID is not tolerated (if irritation occurs), then Bryhali will be used as a “rescue 
treatment” once daily for 1 week before the subject returns to BID treatment with Duobrii. 
If irritation recurs, subjects will be instructed to alternate Duobrii and Bryhali (ie Duobrii 
BID one day, followed by Bryhali QD the next day, Duobrii BID the next, and so on). 
Alternating topical steroid use and stepping down topical steroid strength have been 
known to reduce lesion count in AKN.3  If irritation continues to persist, then participants 
will be instructed to use Bryhali QD for five days a week and Duobrii BID two days a week. 
If participants still experience irritation with this regimen, then subjects will be transitioned 
entirely to Bryhali QD for the remainder of the study. In case of clearance earlier than the 
end of the study, participants will be instructed to continue their respective regimen to 
completion of the study. Gentle hair care regimen will be recommended for duration of 
the length of the study; with unscented shampoo & conditioner (such as Head & shoulder) 
and Vaseline to scalp as moisturizer to minimize risk of contact dermatitis. In addition, 
patients will be instructed to postpone any form of hair coloring or chemical hair 
processing until after the study is over. 
Participants will be followed with visits scheduled at baseline, 4 weeks, 8 weeks and 12 
weeks. At each visit, participants will complete surveys regarding the severity of AKN’s 
associated symptoms (pain, pruritus, burning etc.) as well as the dermatology quality of 
life index (DLQI) and numerical rating scale (NRS) surveys (Appendix B&D). In addition, 
photographs will also be obtained for global assessment and lesion count will be 
performed. The investigator will assess the treatment area for any dyspigmentation and 
document the % area affected within the treatment area at each visit. Tape strips will also 
be collected from lesional (occipital scalp) and non-lesional (frontal scalp) at Baseline and 
Week 12. There will be a phone call visit at week 5 to assess tolerance of medication 
increase and a safety follow-up visit at Week 14. Statistical analysis will be performed. 
Throughout the length of the study, any adverse events (AEs) related to the treatment will 
be recorded.
Effective Date: 8/1/2023
End Date:7/31/2024

4
PATIENT POPULATION:
Prior to enrollment, all subjects must meet the following inclusion and exclusion criteria:
Inclusion criteria:
1. Male or female subject at least 18 years of age
2. Subject is able to provide written informed consent and comply with the 
requirements of this study protocol
3. Subjects have AKN class I or II (less than 6.5 cm in width)
4. Subjects who are women of childbearing potential (WOCBP) must have a 
negative urine pregnancy test at screening and must be practicing an adequate 
and medically acceptable method of birth control for at least 30 days prior to Day 
0 and at least 6 months after the last dose of study. Acceptable methods of birth 
control include intrauterine device (IUD) oral, transdermal, implanted or injected 
hormonal contraceptives (must have been initiated at least 1 month before 
entering the study); tubal ligation; abstinence; barrier methods with spermicide. If 
not of child-bearing potential, subjects must have a sterile or vasectomized 
partner; have had a hysterectomy, a bilateral oophorectomy or be clinically 
diagnosed infertile; or be in a menopausal state for at least a year.
5. Subject is judged to be in good general health as determined by the principal 
investigator.
Exclusion criteria:
1. Unable to understand and provide written consent
2. Have received prior intralesional steroids for AKN within the past 6 months
3. Are using topical steroids or topical medications on their scalp within 4 weeks
4. Have used Duobrii on the scalp for AKN or other scalp disorders
5. Subject is pregnant or breastfeeding
6. Use of prior systemic medication for AKN or acne (doxycycline or isotretinoin) or 
hair loss in the last 6 months
7. Currently using topical minoxidil or prior use within the past 3 months
8. Have a history of other or other active scalp/hair disease or other forms of or 
other forms of alopecia
9. Are on systemic steroids or other immunosuppressants
10.Have a history of auto-immune disease, thyroid disorder, or hypersensitivity to 
steroids.
FUTURE TAPE-STRIP ANALYSIS:
Tape strips will be obtained to characterize the differential gene expression profile of 
affected areas with AKN before and after treatment. Comparative gene-expression 
profiling of the treated and untreated sides will then be performed to characterize the 
exact molecular pathogenesis of AKN. These samples will be frozen and stored until 
additional funding sources are obtained to cover the expenses associated with the 
processing and analyses of the tape strips. 
Effective Date: 8/1/2023
End Date:7/31/2024

5
RANDOMIZATION:
Once a subject meets all the inclusion and exclusion criteria, they will be assigned a 
randomization number on day 0/baseline. Enrolled subjects will be randomized in a 2:1 
ratio of Duobrii to placebo.
The randomization will be performed by designated research staff/personnel at the Icahn 
School of Medicine using a randomization generator. The subjects and assessors (sub-
investigators) will remain blinded to individual treatment assignment during the study. 
Research staff will also be responsible for blinding of the medication.
INVESTIGATIONAL DRUG SUPPLY:
Study medication will be given to subjects at their baseline visit and subsequent visits as 
needed. All study medication will be stored in a secured area at 20° to 25°C.
Unblinded research personnel will dispense study drug in an opaque bag to the subject. 
Individuals will be instructed not to reveal the study drug to anyone except the unblinded 
research staff.
Investigators will instruct subjects on how to approximately measure 1g per application. 
Amount of product requested:
Duobrii = (2 x 100 g tube) or 200g/subject x 20 subjects
Bryhali = (2 x 100 g tube) or 200 g/subject x 20 subjects
Vehicle= (3 x 60 g tube) or 180 g/subject x 10 subjects
DATA ANALYSIS:
 
Sample Size Considerations
A sample size of n=20 Duobrii-treated subjects allows 80% power at 5% significance to 
detect a minimum reduction of 35% in the median number of lesions at week 12 with the 
one-sided Wilcoxon nonparametric test. This calculation assumes an average count of 
15 AKN lesions at baseline and a standard deviation of 7 lesions around the mean 
difference at week 12, and a drop-out rate of 30%. These numbers are based on data 
reported by Okoye et al. (2014), who compared lesion counts at week 16 to baseline in a 
set of 11 UVB-treated subjects. The sample size calculation is based on the asymptotic 
relative efficiency of the Wilcoxon test compared to paired Student’s t-test. A sample size 
of n=20 treated subjects compared to n=10 placebo-treated ones allows 80% power at 
5% significance to detect a minimum 50% difference between proportions of patients with 
a reduced number of AKN lesions. This calculation is based on the application of a one-
sided Z-test for the difference between two independent proportions and also assumes a 
maximum 30% dropout rate within each arm.
Effective Date: 8/1/2023
End Date:7/31/2024

6
Primary Endpoint 
 
The primary analysis for the primary endpoint will test for a reduction in lesion counts after 
12 weeks of treatment. We will apply the two-sided Wilcoxon test to assess the 
significance of the difference between pre- and post-treatment median numbers of lesion 
counts. The secondary analysis will compare the reduction in lesion counts between 
active and placebo groups after 12 weeks. For this purpose, we will apply the Z-test to 
verify the hypothesis that the proportions of patients with reduced AKN lesions differ 
between active and placebo groups. A more comprehensive analysis will adjust a 
generalized linear mixed-effects model, based on Poisson distribution, including time and 
treatment group as fixed factors and a random intercept for each subject. This model will 
include the whole time-course and contrasts of interests will be estimated.
 
Secondary Endpoints
 
We will compare the improvement in the severity of AKN symptoms, degree of 
dyspigmentation, and patient-reported outcomes (DLQI and NRS) between time points 
(Baseline, 4, 8, and 12 Weeks) and groups (placebo and active) with the nonparametric 
tests described for the primary endpoint. We will also adjust, for each outcome, a 
generalized linear mixed-effects model including time, treatment group, their interaction 
as fixed effects, and a random intercept for each participant. This modeling strategy will 
decide each outcome's probabilistic distribution and link function based on goodness-of-
fit criteria. The Spearman correlation coefficient will measure the association between 
reduction in lesion counts and improvement in patient-reported outcomes.  In addition, 
we will compare the percent area of the treatment area affected with dyspigmentation 
(hypo- or hyperpigmentation) at each visit.  
 
SAFETY MONITORING
The study will be conducted in accordance with our department’s Standard Operating 
Procedures, which are based on US FDA Title 21 Code of Federal Regulations and ICH 
Good Clinical Practice guidelines.  
An investigator will review all laboratory results and assess for adverse events.  The 
principal investigator will be informed of all adverse events.  In the event that a subject’s 
safety is compromised, the investigator will discontinue the subject immediately.  
POTENTIAL RISKS
Duobri:
Participants will be advised to avoid a severe sunburn and/or prolonged periods of 
sunlight exposure. If a sunburn does occur, subjects will be instructed to consult with their 
Effective Date: 8/1/2023
End Date:7/31/2024

7
healthcare provider and discontinue Duobrii until sunburn is healed. Hats or other head 
coverings will be strongly encouraged if direct sunlight exposure is unavoidable.
The following side effects are grouped by likelihood and severity.
Serious Reactions:

HPA axis suppression (prolonged use)

Cushing syndrome (prolonged use)

Hyperglycemia (prolonged use)

Cataracts (prolonged use)

Glaucoma (prolonged use)

Intracranial HTN (prolonged use in pediatric patients)
Common Reactions:

Allergic contact dermatitis

Application site pain

Folliculitis

Skin atrophy 

Excoriation

Burning

Pruritus

Irritation

Dryness

Hypertrichosis

Acneiform dermatitis

Hypopigmentation

Perioral dermatitis

Maceration

Secondary infection

Striae

Milaria

Photosensitivity
Bryhali:

URI (lotion form)

Stinging

Burning

Pruritis

Irritation

Dryness

Skin atrophy

Folliculitis

Hypertrichosis

Aceneiform dermatitis
Effective Date: 8/1/2023
End Date:7/31/2024

8

Hypopigmentation

Perioral dermatitis

Allergic contact dermatitis

Maceration

Secondary infection

Striae

Miliaria
For further safety information on Duobrii and Bryhali, refer to the respective package 
inserts.
CONTRAINDICATIONS/CAUTIONS:
Duobrii: 1) Hypersensitivity to drug/class/compound 2) Pregnancy 3) Breastfeeding if 
applied on nipples 4) Female patients of reproductive potential 5) Pediatric patients 6) 
Skin infection 7) Photosensitivity 8) Sunburn 9) History of skin cancer 
Bryhali: 1) Hypersensitivity to drug/class/compound 2) Pediatric patients 3) Skin infection
Definition of an AE: Any untoward medical occurrence in a subject administered a 
pharmaceutical product that does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
a medicinal (investigational) product, whether or not considered related to the 
investigational medicinal product.
Investigational Medicinal Product (IMP) includes the drug under evaluation and the 
comparator drug(s) if specified as part of the research objective, given at any time during 
the study. Medical conditions/diseases present before starting the drug of interest are 
only considered adverse events if they worsen after starting the drug of interest.
The occurrence of adverse events will be sought by non-directive questioning of the 
patient at each visit during the study. Adverse events also may be detected when they 
are volunteered by the patient during or between visits or through physical examination, 
laboratory test, or other assessments. All adverse events will be recorded in the study 
database including the following information:
1. the severity grade (mild, moderate, severe) 
2. its relationship to the drug(s) of interest (suspected/not suspected)
3. its duration (start and end dates or if continuing at final exam)
4. whether it constitutes a serious adverse event (SAE)
A SAE is any untoward medical occurrence that at any dose:
-
results in death
-
is life-threatening
-
requires inpatient hospitalization or prolongation of existing hospitalization
-
results in persistent or significant disability/incapacity
Effective Date: 8/1/2023
End Date:7/31/2024

9
-
is a congenital anomaly/birth defect 
-
is otherwise a significant medical event
This includes any SAEs likely to arise from the trial indication or progression of 
underlying/concomitant illness(es) (e.g. progression of cancer in oncology trials), unless 
specified in the protocol as study specific exemptions.
Any SAE, irrespective of causality, occurring after the subject has provided informed 
consent and until four weeks after the subject has stopped study participation must be 
reported unless otherwise stated in the protocol. SAEs occurring after four weeks from 
ending study participation should only be reported if considered by the Investigator 
attributable to the exposure to the investigational drug(s) during the trial period. This 
includes the period in which the study protocol interferes with the standard medical 
treatment given to a subject, even if study treatment has not yet started (e.g. withdrawal 
of previous treatment during washout period, change in treatment to a fixed dose of 
concomitant medication).
Timelines: All serious adverse events (SAEs) from interventional clinical trials must be 
reported by the sites to the Lead PI within 24 hours of occurrence of the SAE and to the 
site’s own IRB as required. The Lead PI will then report to the manufacturer and any other 
authorities. 
Follow-up reports: All related SAEs will be followed until resolution or until it is judged 
to be permanent, and an assessment will be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the drug of interest, 
the interventions required to treat it, and the outcome. 
Pregnancies: Any occurrences of a pregnancy in a patient (or a patient’s partner) during 
study participation will be collected. All pregnancies will be followed up to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications.
Should a temporary or permanent suspension occur, we would report the occurrence to 
all appropriate authorities.
DISCONTINUATION OF TREATMENT AND WITHDRAWAL OF SUBJECTS:
The reasons why a subject may discontinue or be withdrawn from the study by the 
investigator include, but are not limited to the following: subject request, protocol violation, 
loss to follow up, subject non-compliance, study termination by investigators, and a 
confirmed grade 3 or higher adverse event, which is suspected to be related to test article 
administration.
Effective Date: 8/1/2023
End Date:7/31/2024

10
Participants will be given a standard calendar dosing diary that will allow them to place 
checkmarks each day that study drug was taken. Investigators will assess diary at all in-
person visits (weeks 4, 8, and 12). Subjects will be terminated from study if they do not 
maintain ≥50% dosing compliance.
REFERENCES:
1. Olsen EA, Bergfeld WF, Cotsarelis G, et al. Summary of North American Hair 
Research Society (NAHRS)-sponsored Workshop on Cicatricial Alopecia, Duke 
University Medical Center, February 10 and 11, 2001. J Am Acad Dermatol. 
2003;48(1):103-110. doi:10.1067/mjd.2003.68
2. Umar S, Lee DJ, Lullo JJ. A Retrospective Cohort Study and Clinical Classification 
System of Acne Keloidalis Nuchae. J Clin Aesthetic Dermatol. 2021;14(4):E61-
E67.
3. Ogunbiyi A. Acne keloidalis nuchae: prevalence, impact, and management 
challenges. 
Clin 
Cosmet 
Investig 
Dermatol. 
2016;9:483-489. 
doi:10.2147/CCID.S99225
4. Okoye, G. A., Rainer, B. M., Leung, S. G., Suh, H. S., Kim, J. H., Nelson, A. M., 
Garza, L. A., Chien, A. L., & Kang, S. (2014). Improving acne keloidalis nuchae 
with targeted ultraviolet B treatment: a prospective, randomized, split‐scalp 
comparison study. British Journal of Dermatology, 171(5), 1156–1163. 
https://doi.org/10.1111/bjd.13119.
Effective Date: 8/1/2023
End Date:7/31/2024

11
Appendix A.
Schedule of Events
Screening
Baseline
W4
W5c
W8
W12
W14d
ET
Visit number
1
1a
2
3
4
5
6
TBD
Informed consent
X
Medical History
X
Demographics
X
Inclusion/Exclusion
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
Pregnancy Testb
X
X
X
X
X
X
Administer IP
X
Assess IP Compliance
X
X
X
X
Return IP
X
X
DLQI
X
X
X
X
X
NRS
X
X
X
X
X
AKN severity
X
X
X
X
X
Clinical Photographs
X
X
X
X
X
Clinical Assessment/ 
Lesion Count
X
X
X
X
X
X
Tape strips (lesional & non-
lesional)
X
Tape strips (lesional only)
X
a.
If screening is successful, patient will continue into their Baseline visit on same day.
b.
Where applicable, a urine pregnancy test with high sensitivity to HCG will be performed at screening and 
at all other visits, prior to dosing female participants of childbearing potential with Investigational Product 
(IP).  
c.
Phone call visit
d.
Follow up visit
Effective Date: 8/1/2023
End Date:7/31/2024

1 2
A p p e n di x B.
D E R M A T O L O G Y LI F E Q U A LI T Y I N D E X ( D L QI)     
T h e ai m of t hi s q u e sti o n n air e i s t o m e a s ur e h o w m u c h y o ur s ki n pr o bl e m h a s aff e ct e d 
y o ur lif e O V E R T H E L A S T W E E K.  Pl e a s e c h e c k o n e b o x f or e a c h q u e sti o n.
1.
O v er t h e l a st w e e k, h o w it c h y, s or e , p ai nf ul  or sti n gi n g  
h a s y o ur s ki n b e e n ?
V er y 
m u c h
A l ot
A littl e
N ot at all




2.
O v er t h e l a st w e e k, h o w e m b arr a s s e d  or s elf c o n s ci o u s  
h a v e y o u b e e n b e c a u s e of y o ur s ki n ?
V er y 
m u c h
A l ot
A littl e
N ot at all




3.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n i nt erf er e d 
wit h y o u g oi n g s h o p pi n g  or l o o ki n g aft er y o ur h o m e  or 
g ar d e n ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

4.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n i nfl u e n c e d 
t h e cl ot h e s  y o u w e ar ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

5.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n aff e ct e d a n y 
s o ci al  or l ei s ur e a cti viti e s ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

6.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n m a d e it 
diffi c ult f or y o u t o d o a n y s p ort ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

7.
O v er t h e l a st w e e k, h a s y o ur s ki n pr e v e nt e d y o u fr o m 
w or ki n g  or st u d yi n g ?
y e s
n o


N ot r el e v a nt 

Eff e cti v e D at e: 8/ 1/ 2 0 2 3
E n d D at e: 7/ 3 1/ 2 0 2 4

1 3
If "N o ", o v er t h e l a st w e e k h o w m u c h h a s y o ur s ki n b e e n a 
pr o bl e m at w or k  or st u d yi n g ?
A l ot
A littl e
N ot at all 



8.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n cr e at e d 
pr o bl e m s wit h y o ur p art n er  or a n y of y o ur cl o s e fri e n d s or 
r el ati v e s? 
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

9.
O v er t h e l a st w e e k, h o w m u c h h a s y o ur s ki n c a u s e d a n y 
s e x u al diffi c ulti e s ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

1 0. O v er t h e l a st w e e k, h o w m u c h of a pr o bl e m h a s t h e 
tr e at m e nt f or y o ur s ki n b e e n, f or e x a m pl e b y m a ki n g y o ur 
h o m e m e s s y, or b y t a ki n g u p ti m e ?
V er y 
m u c h
A l ot
A littl e
N ot at all




N ot r el e v a nt 

Eff e cti v e D at e: 8/ 1/ 2 0 2 3
E n d D at e: 7/ 3 1/ 2 0 2 4

14
Appendix C.
Effective Date: 8/1/2023
End Date:7/31/2024

15
Appendix D.
The Numeric Pain Rating Scale Instructions
Please indicate the intensity of current, best, and worst pain levels over the past 7 days 
on a scale of 0 (no pain) to 10 (worst pain imaginable).
The Numeric Itch Rating Scale Instructions
Please indicate the intensity of current, best, and worst itch levels over the past 7 days 
on a scale of 0 (no itching) to 10 (worst itching imaginable).
Effective Date: 8/1/2023
End Date:7/31/2024

16
Appendix E.
Amendment # 1 Dated 03 Oct 2022 List of Revisions
Page 1 Title page: Added: Amendment #1 Version:03 October 2022
Page 2 Primary Hypothesis: added “as” …symptoms associated with AKN as well as 
minimal dyspigmentation when compared to patients receiving placebo.
Page 3 Study Design Overview 2nd paragraph added: …recruitment will be conducted 
at various local barber shops and social media platforms (instagram, twitter and facebook) 
to increase patient recruitment. 
Page 3 Study Design Overview last paragraph: added “The investigator will assess 
the treatment area for any dyspigmentation and document the % area affected within 
the treatment area at each visit.”
Page 4 Exclusion Criteria Revised criterion # 6: Use of prior systemic medication for 
AKN or acne (doxycycline or isotretinoin) or hair loss in the last 6 months.
Page 6 Data Analysis / Secondary Endpoints, added: In addition, we will compare the 
percent area of the treatment area affected with dyspigmentation (hypo- or 
hyperpigmentation) at each visit.  
Page 10 References – moved ahead of all Appendices. 
Page 16 Appendix E – Amendment # 1 list of Revisions added 
Effective Date: 8/1/2023
End Date:7/31/2024

17
 Amendment # 2 Dated 26 Oct 2022 List of Revisions
Page 1 Title page: Added: Amendment #2 Version:26 October 2022
Page 11 Appendix A: Deleted “Where applicable, serum BHCG at screening, urine 
tests at all other visits to be performed prior to dosing female participants of childbearing 
potential with Investigational Product (IP) Two negative pregnancy tests are required 
before receiving IP (1 negative Serum Pregnancy Test at Screening and 1 negative 
Urine pregnancy test at the baseline visit before IP administration). 
Added… “Where applicable, a urine pregnancy test with high sensitivity to HCG will be 
performed at screening and at all other visits, prior to dosing female participants of 
childbearing potential with Investigational Product (IP). “
Page 17 – Amendment # 2 list of Revisions added 
Effective Date: 8/1/2023
End Date:7/31/2024