A Phase 2 Multi-Center, Randomized, Double-Blind, Vehicle-Controlled Ascending Dose Study of SB206 in Subjects With Molluscum Contagiosum
Phase: PHASE2
Conditions: Molluscum Contagiosum
Sponsor: Novan, Inc.

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
SB206/NVN1000 
DRUG: 
SB206/NVN1000 
STUDY NUMBER(S): 
NI-MC201 
PROTOCOL(S) TITLE: 
A PHASE 2 MULTI-CENTER, RANDOMIZED, 
DOUBLE-BLIND, VEHICLE-CONTROLLED, 
ASCENDING DOSE STUDY OF SB206 IN 
SUBJECTS WITH MOLLUSCUM CONTAGIOSUM 
IND NUMBER: 
137015 
SPONSOR: 
Novan, Inc 
ORIGINAL PROTOCOL DATE: 
10 November 2017 
VERSION NUMBER: 
Version 3.0 
AMENDMENT VERSION DATE: 
29 June 2018 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscurn Contagiosurn Ascending Dose Study 
SB206!NVN1000 
CLINICAL PROTOCOL APPROVAL FORM 
Protocol Title: A PHASE 2 MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, VEIDCLE-
CONTROLLED, ASCENDING DOSE STUDY OF SB206 IN SUBJECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Study No: NI-MC201 
Original Protocol Date: 10 November 2017 
Protocol Version No: 3.0 
Protocol Amendment Version Date: 29 June 2018 
This study protocol was subject to critical review and has been approved by the appropriate 
protocol review committee of Novan. The information contained in this protocol is consistent 
with: 
• 
The current risk-benefit evaluation of the investigational product. 
• 
The moral, ethical and scientific principles goveming clinical research a'> set out in the 
Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 54, 56 
and 312 and according to applicable local requirements. 
The Investigator will be supplied with details of any significant or new findings, including 
adverse events, relating to treatment with the investigational product. 
Name and Title 
Author: 
Teresa Reams, Clinical Study Manager 
Clinical Operations: 
Emily de Leon, Director of Clinical 
Development 
Biometrics: 
Todd Durham, Head of Biostatistics 
Medical Lead: 
Tomoko Maeda-Chubachi, VP, Medical 
Dermatology 
Regulatory Affairs: 
Kevin Barber, VP, Regulatory Affairs 
Quality Assurance: 
Liz Troll, Head of Clinical Quality 
Assurance 
Approval 
No 
one) 
No 
No 
(circle one) 
Yes 
No 
(circle one) 
No 
(circle one) 
Yes 
No 
(circle one) 
Signature 
Date 
.:J..v.._._. L-
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16.1.1 Protocol Nl-MC20 I, Amendment 2 
Novan: 1\ Phase 2 Molluscurn Contagiosurn Ascending Dose Study 
SB206/NVN 1000 
CLINICAL PROTOCOL APPROVAL FORM 
Protocol Title: A PHASE 2 MUL Tl-CENTER, RANDOMIZED, DOUBLE-BLIND, VEHICLE-
CONTROLLED, ASCENOING DOSE STUDY OF SR206 IN SUR.IECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Study No: Nl-MC20t 
Original Protocol Date: lO November 2017 
Protocol Version No: 3.0 
Protocol Amendment Version Date: 29 June 2018 
This study protocol was subject to critical review and has been approved by the appropriate 
protocol review committee of Novan. The information contained in this protocol is consistent 
with: 
• 
The current risk-benefit evaluation of the investigational product. 
• 
The moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 54, 56 
and 312 and according to applicable local requirements. 
The Investigator will be supplied with details of any significant or new findings, including 
adverse events. relating to treatment with the investigational product. 
-
Name and Title 
Approval 
Signature 
Date 
--
----
-
-
-
Author: 
Yes 
No 
Teresa Reams, Clinical Study Manager 
(circle one) 
-
--
--
--
-
~ 
-
Clinical Operations: 
Yes 
No 
Emily de Leon. Director of Clinical 
(circle one) 
Development 
---
-
>-- ·-
Biometrics: 
Yes 
No 
Todd Durham, Head of Biostatistics 
(circle one) 
-
-
Medical Lead: 
(:!_cJ 
No 
611/ 
Tomoko Maeda-Chubachi, VP, Medical 
-7/l 
/L--t.,~ 
Dermatology 
(circle one) 
__,,,.= 
I 
-
Regulatory Affairs: 
Yes 
No 
Kevin Barber, VP, Regulatory Atfairs 
(circle one) 
Quality Assurance: 
Yes 
No 
Liz Troll, Head of Clinical Quality 
(circle one) 
Assurance 
--

16.1.1 Protocol NI-MC20 I, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
SB206/NVN I 000 
CLINICAL PROTOCOL APPROVAL FORM 
Protocol Title: A PHASE 2 MVL TI-CENTER, RANDOMIZED, DOUBLE-BLIND, VEHICLE-
CONTROLLED, ASCENDING DOSE STUDY OF 88206 IN SUBJECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Study No: NI-MC201 
Original Protocol Date: 10 November 2017 
Protocol Version No: 3.0 
Protocol Amendment Version Date: 29 June 2018 
This study protocol was subject to critical review and has been approved by the appropriate 
protocol review committee of Novan. The information contained in this protocol is consistent 
with: 
• 
The current risk-benefit evaluation of the investigational product. 
• 
The moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 54, 56 
and 312 and according to applicable local requirements. 
The Investigator wiJJ be supplied with details of any significant or new findings, including 
adverse events, relating to treatment with the investigational product. 
1 Name and Title 
Approval 
Signature 
Date 
Author: 
Yes 
No 
Teresa Reams, Clinical Study Manager 
(circle one) 
CJinicaJ Operations: 
Yes 
No 
Emily de Leo~ Director of Clinical 
(circle one) 
Development 
Biometrics: 
Yes 
No 
Todd Durham, Head of Biostatistics 
(circle one) 
Medical Lead: 
Yes 
No 
Tomoko Maeda-Chubach~ VP, Medical 
(circle one) 
Dermatology 
Regulatory Affairs: 
Yes 
No 
Kevin Barber, VP, Regulatory Affairs 
(circle one) 
Quality Assurance: 
~ !/fa~ 
Yes 
No 
Liz Troll, Head of Clinical Quality 
24~ 
Assurance 
(circle one) 
"2J)IC{ 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
SB206/NVN1000 
RATIONALE FOR AMENDMENT 
This protocol amendment is to 1) add collection of blood samples for analysis of hMAP3 to 
confirm the level of systemic exposure to SB206 and 2) to add an unblinded analysis after all 
subjects have completed Cohort 3.  Administrative changes and clarifications have also been 
included in this amendment.   
IDENTIFICATION OF CHANGES 
Any changes to the original protocol are identified below and are incorporated into this protocol 
amendment.  All additions are identified using bold underlined text.  Any deletions are identified 
using strikethrough text.  The Table of Contents and internal references are updated to reflect 
current section numbers. Minor administrative changes were made as well to correct grammar, 
punctuation, etc. 
Change 1: STUDY SUMMARY: 
STUDY DESIGN: 
Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks to all 
lesions identified at Baseline and new lesions that arise during treatment. If a subject clears all 
lesions (confirmed by the Investigator at the next regular scheduled visit), the treatment period will 
end, and subjects will be followed for recurrence/new lesions until Week 12/ Early Termination 
(ET). All QD dosing should be applied in the morning at home or in the clinic.  All subjects 
should apply their last dose to accommodate the 1 to 6 hour window for blood draws. The 
exact time of the last dose preceding any scheduled visit will be collected.  Subjects will visit 
the clinic at Screening, Baseline, Week 1, Week 2, Week 4, Week 8, and Week 12. 
Change 2: STUDY SUMMARY: 
SECONDARY EFFICACY ENDPOINTS: 
Proportion of subjects achieving  at least a achieving 75% reduction from baseline in the number 
of MC at each visit. 
Change 3: STUDY SUMMARY: 
Exposure Endpoint 
• Determination of the hMAP3 plasma concentration at end of treatment, if quantifiable.
Change 4: LIST OF ABBREVIATIONS 
hMAP3 – Hydrolyzed N-Methylaminopropyl-trimethoxysilane 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
SB206/NVN1000 
Change 5: 1.1 BACKGROUND 
Clinical studies A clinical study involving subjects with psoriasis just completed and one in 
subjects with atopic dermatitis are is ongoing. 
Change 6: 1.1.1 PHARMACOKINETICS 
In the recently completed study in subjects with psoriasis (NI-PS101) who were administered 
a cream formulation, SB414 6% (NVN1000 Ointment 12% co-administered with hydrogel),  
6 of 23 subjects (26.0%) had at least one quantifiable hMAP3 plasma concentration following 
dosing. The mean (SD) Cmax of hMAP3 (18.89 [15.02] ng/mL) occurred at 1 hour postdose 
in the 6 subjects with quantifiable hMAP3 plasma concentrations. The plasma concentration 
gradually decreased after the peak and hMAP3 was below the the lower limit of quantitation 
(LLOQ)  in all subjects at 12 hours postdose. Systemic exposure to the investigational 
product was negligible in the study. The clinical study report is under preparation. Analyses 
are currently ongoing to determine systemic exposure in a study of subjects with atopic 
dermatitis (NI-AD101) administered SB414 2% (NVN1000 Ointment 4% co-administered 
with buffered hydrogel) or 6% (NVN1000 Ointment 12% co-administed with buffered 
hydrogel). 
Change 7: 1.2.1: DOSING REGIMEN 
All QD dosing should be applied in the morning at home or in the clinic.  All subjects should 
apply their last dose to accommodate the 1 to 6 hour window for blood draws.   The exact 
time of the last dose preceding any scheduled visit will be collected. Each dose will consist of 
NVN1000 Gel or Vehicle Gel with an equal volume of hydrogel mixed thoroughly together by the 
subject or caregiver and applied to the lesions and approximately 1 cm surrounding each lesion.  
Periocular lesions will be treated if the lesions are at least 2 cm from the edge of the eye.  Lesions 
on the labia and penis will not be treated.  
Change 8: EXPOSURE ENDPOINT 
3.5 Exposure Endpoint 
Blood for determination of the hMAP3 plasma concentration will be collected at a single time 
point at the end of treatment to evaluate if quantifiable concentrations can be measured 
following repeated application. 
Change 9: 4.1 STUDY DESIGN 
Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks to all 
lesions identified at Baseline and new lesions that arise during treatment. If a subject clears all 
lesions (confirmed by the Investigator at the next regular scheduled visit), the treatment period will 
end, and subjects will be followed for recurrence/new lesions until Week 12/ET.  All QD dosing 
should be applied in the morning at home or in the clinic.  All subjects should apply their 
last dose to accommodate the 1 to 6 hour window for blood draws.   The exact time of the 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study  
SB206/NVN1000 
 
 
 
last dose preceding any scheduled visit will be collected. Subjects will visit the clinic at 
Screening, Baseline, Week 1, Week 2, Week 4, Week 8, and Week 12/ET. 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study  
Confidential
SB206/NVN1000 
Page 6 of 68
 
 
 
Change 10: Table 1: Schedule of Assessments 
Screening1 
(Day -28 to 
Day 1) 
Visit 11 
Baseline 
(Day 1) 
Visit 22 
Week 1 
(Day 8 ±3) 
Visit 32 
Week 2 
(Day 15 ±3) 
Visit 42 
Week 4 
(Day 29 ±3) 
Visit 52 
Week 8 
(Day 57 ±3) 
Visit 62 
Week 12/ET 
(Day 85 ±7) 
Informed Consent (Assent) 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
X 
 
 
 
 
 
Lesion Counts 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
  
X 
 
  
  
  
 X 
Vital Signs 
  
X 
X 
X 
X 
X 
X 
Chemistry & Hematology3 
 
X 
 
  
  
  
 X 
Methemoglobin34 
  
X 
X 
X 
X 
X 
X 
Assessment of hMAP3 plasma 
concentration5,6 
 
 
 
 
 
 
X 
Urine Pregnancy Test57 
X 
X 
 
  
X 
X 
X 
Tolerability Evaluation 
  
X 
X 
X 
X 
X 
X 
Photographs6  
  
X 
 
 
X 
 
X 
In Clinic Study Drug Application and Provide 
Subject Instructions 
 
X 
 
 
 
 
 
Dispense Subject Diary 
 
X 
 
 
X 
X 
 
Review Study Compliance 
 
 
X 
X 
X 
X 
X 
Collect Subject Diary 
 
 
 
 
X 
X 
X 
Drug Dispensed 
 
X 
 
 
X 
X 
 
Collect Study Drug 
 
 
 
 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Review Concomitant Medications and 
Adverse Events  
 
X 
X 
X 
X 
X 
X 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 7 of 68
1 Screening and Baseline may occur on the same day. 
2 All visit dates are in reference to Baseline, e.g. Week 1 occurs 7 days after Baseline Visit. 
3Collected at the last day of treatment. 
4Collected via pulse co-oximetry at site. 
5 Blood for determination of the hMAP3 plasma concentration will be collected at a single time approximately 1 to 6 hours following last dose 
application.  The time of the sample collection and the time of last dose preceding the scheduled visit will be recorded.  The blood sample may be 
collected at the same time as the chemistry and hematology sample.   
56Selected sites and subjects. 
7Females 10 years of age and older. Subjects whose Baseline is within 7 days of Screening do not require UPT retesting.
67Selected sites and subjects.

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 8 of 68
Change 11: 5.4.1 SCREENING FAILURES 
Subjects will not be allowed to rescreen. 
Change 12: 6.1 GENERAL INSTRUCTIONS 
The first application should be done at the clinic. All study drug applications will be done at 
home except for the first dose on Day 1. 
Change 13: 6.2.1: SCREENING (DAY -28 TO Day 1) 
3. Obtain subject’s medical history (including start date of the subject’s current episode of
molluscum (i.e., when molluscum was first noticed by the subject/caregiver), medication
history and concomitant medication information. 
Change 14: 6.2.4: VISIT 3/WEEK 2 (DAY 15±3) 
6. If subject discontiues treatment, collect blood samples for chemistry, hematology and
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
Change 15: 6.2.5: VISIT 4/WEEK 4 (DAY 29±3) 
6. If subject discontiues treatment, collect blood samples for chemistry, hematology and
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
Change 16: 6.2.6: VISIT 5/WEEK 8 (DAY 57±3) 
6. If subject discontiues treatment, collect blood samples for chemistry, hematology and
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
Change 17: 6.2.7 VISIT 6/WEEK 12/ET (DAY 85 ±7) 
3. If subject is still on treatment, collect blood samples for chemistry, hematology and
hMAP3 and  confirm time of last dose with subject/caregiver or apply dose in clinic. 
3. Collect blood samples for chemistry and hematology.
Change 18: 7.3.3 CLINICAL LABORATORY TESTS 
Chemistry and hematology will be collected at Baseline and Week 12/ET on the last day of 
treatment.  Clinically significant changes in laboratory values will be recorded as AEs. 
Change 19: 7.4 EXPOSURE ASSESSMENT 
7.4 EXPOSURE ASSESSMENT 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 9 of 68
At select sites, a blood sample will be collected at the Week 12 visit from those subjects who 
have not previously discontinued treatment.  The sample will be collected at a single time 
point approximately 1 to 6 hours following application of study drug.  The final dose may be 
either be done at home or in the clinic.  The time of dose application and sample collection 
should be recorded.  Blood may be collected at the same time as the chemistry and 
hematology sample, but the chemistry and hematology samples should be drawn first. If a 
subject discontinues treatment for any reason (e.g., lesion clearance, subject withdrawal, 
physician decision) before Visit 6, blood should be collected on the last day of treatment.  
Instructions for processing and transporting plasma samples for analysis will be described 
separately. 
Change 20: 8.4 BLINDING AND UNBLINDING TREATMENT ASSIGNMENT 
All subjects, investigators, and study personnel involved in the conduct of the study will be blinded 
to treatment assignment, with the exception of a specified unblinded statistician from Premier 
Research who will generate and have access to the randomization code. The unblinded study 
personnel will not otherwise participate in study procedures or data analysis prior to unblinding of 
the study data to all study related personnel.  
Several analyses of unblinded data are planned throughout the study. A Data Safety 
Monitoring Board (DSMB) will conduct an unblinded review of safety and tolerability data after 
30 subjects are enrolled and treated for two weeks within in each cohort. Unblinded personnel who 
are not otherwise involved in the study will prepare the data for review.   After all subjects in 
Cohort 3 have completed their last study visits, the database for all subjects in Cohorts 1-3 
will be frozen for purposes of an interim analysis of safety and efficacy data.  While this 
interim analysis is being prepared, the study will complete through Cohort 4 and the final 
analysis will be based on all subjects in Cohorts 1-4: Cohort 4 (QD dosing of SB206 8% or 
12% vs. vehicle).  Personnel who are not otherwise involved in the study will prepare the 
unblinded data and summary tables for the interim analysis.  
Study personnel will endeavor to safeguard the integrity of the study blind to minimize bias in the 
conduct of the study. Individual Ttreatment unblinding is discouraged since knowledge of the 
treatment assignment will not materially change the planned management of a medical emergency. 
Change 21: 8.6 ACCOUNTABILITY 
Study drug returned by subjects at Weeks 4 and 8 will be held on site until final accountability has 
been completed. Upon completion or termination of the study, tThe site will be instructed on return 
or destruction of used and unused clinical supplies. 
Change 22: 11.1 General Procedures 
Prior to the database lock release of unblinded information through Cohort 3, a detailed, 
finalized Statistical Analysis Plan (SAP) will be completed and placed on file.  

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study  
Confidential
SB206/NVN1000 
Page 10 of 68
 
 
 
Change 23: 11.3 ANALYSIS POPULATIONS 
The exposure population will consist of all subjects who receive at least 1 application of active 
study medication and had a blood sample collected and successfully analyzed for the hMAP3 
plasma concentration. 
The per-protocol population (PP) will consist of all subjects in the mITT population and have no 
significant protocol deviations that impact the analyses of the efficacy endpoints.  
Change 24:11.4.1 DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
Subject demographic and Baseline characteristics will be summarized by treatment group and 
overall for the SAF, mITT and ITT populations. Relevant medical history, current medical 
conditions, and any other relevant information will be listed by subject. 
Change 25: 11.4.2 EFFICACY ANALYSIS 
Secondary endpoints will be analyzed on the mITT and ITT population as follows: 
Change 26: 11.4.3.4 LABORATORY ASSESSMENTS 
Blood chemistry and hematology values will be reported individually at Baseline and day of last 
dose, which may occur at any time during the study.  Therefore, the study day of the last 
dose will be used to assign the laboratory values to the closest study visit (Week 1, 2, 4, 8, or 
12/ET).  Laboratory test results will be summarized descriptively at Baseline and Week 12/ET 
each visit.  Additionally, shifts from Baseline to Week 12/ET each visit in laboratory test results 
based on normal ranges will be summarized with descriptive statistics.  The last laboratory 
evaluation prior to the first dose of study drug will be used as Baseline for all laboratory analyses.  
Any clinically significant changes from Baseline will be documented as an AE. 
Change 27:11.5 ANALYSIS OF hMAP3 PLASMA CONCENTRATIONS 
11.5 Analysis of hMAP3 Plasma Concentrations 
Plasma concentrations of hMAP3, a silicon-containing hydrolyzed monomer of the 
polymeric NVN1000 drug substance will be determined.  Results will be presented in data 
listings by subject.  If quantifiable concentrations are observed, the results will be 
summarized descriptively.  
Change 28: 11.6 INTERIM ANALYSIS 
No interim analyses are planned for this study. 
After all subjects in Cohort 3 have completed their last study visits, the database for all 
subjects in Cohorts 1-3 will be frozen for purposes of an interim analysis of safety and 
efficacy data.  While this interim analysis is being prepared, the study will complete 
through Cohort 4 and the final analysis will be based on all subjects in Cohorts 1-4: Cohort 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study  
Confidential
SB206/NVN1000 
Page 11 of 68
 
 
 
4 (QD dosing of SB206 8% or 12% vs. vehicle).   Personnel who are not otherwise involved 
in the study will prepare the unblinded data and summary tables for the interim analysis.  
The interim analysis will not impact the final analysis since the study does not involve any 
formal hypothesis testing.   
Change 29: 12.1 GOOD CLINICAL PRACTICE 
The Investigator must submit all essential regulatory documentation, as required by local and 
national regulations (including approval of the protocol and informed consent/assent form by an 
IRB) to Premier Research the CRO before investigational product will be shipped to the study 
site. 
Change 30: 13.2 MONITORING 
All aspects of the study will be monitored by Premier the CRO or Novan according to Good 
Clinical Practices (GCP) and Standard Operating Procedures (SOPs) for compliance with 
applicable government regulations, (i.e., informed consent regulations, (21 C.F.R. § 50.20, 1999), 
and Institutional Review Board regulations, (21 C.F.R. § 56.103, 1981)). 
 
 
 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 12 of 68
NI-MC201 
A Phase 2 Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, Ascending Dose 
Study of SB206 in Subjects with Molluscum Contagiosum 
CONFIDENTIALITY AND INVESTIGATOR’S STATEMENT 
The information contained in this protocol and all other information relevant to SB206 are the 
confidential and proprietary information of Novan, Inc (Novan), and except as may be required by 
federal, state or local laws or regulation, may not be disclosed to others without prior written 
permission of Novan, Inc. 
I have read the protocol, including all appendices, and I agree that it contains all of the necessary 
information for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in accordance with the regulations stated in the Federal Code of Regulations (CFR) 
for Good Clinical Practices (GCP) and International Conference on Harmonization (ICH) 
guidelines and will make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Novan, Inc or specified designees. I will 
discuss the material with them to ensure that they are fully informed about SB206 and the study. 
___________________________________ 
_________________________________ 
Principal Investigator Name (printed) 
Signature 
__________________________________ 
_________________________________ 
Date 
 
Site Number 

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 13 of 68
STUDY SUMMARY 
Title: 
A Phase 2 Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, 
Ascending Dose Study of SB206 in Subjects with Molluscum Contagiosum 
Rationale: 
Molluscum Contagiosum (MC) is benign and generally self-limiting. The 
average duration of a single lesion is about 2 months; however, since the 
lesions spread easily by autoinoculation from scratching or trauma, the 
duration of infection is often more than a year.  
There is a significant, unmet medical need to treat MC, considering most 
patients with MC are healthy young children. Ablative treatment often causes 
fear to the children and interfere in physician-patient relationships. Repeated 
ablative treatment become difficult. Topical application of SB206 which 
releases nitric oxide may accelerate resolution of MC without causing pain, 
and provide an effective, safe and convenient treatment option of MC. 
Target 
Population: 
Males and females, 2 years of age and older, with a minimum of 3 and a 
maximum of 70 MC lesions at baseline. 
Number of 
Subjects: 
Approximately 192 subjects with a possibility to increase up to 256 subjects. 
Objectives: 
This study is being conducted to evaluate the efficacy, safety and tolerability 
of SB206 for the topical treatment of MC. Results will be used to determine 
the dose(s) for future studies.  
Study Design: This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled 
ascending dose study to be conducted in up to approximately 192 or 256 non-
immunocompromised subjects with molluscum contagiosum. After obtaining 
informed consent, subjects who satisfy entry criteria will be randomized 3:1 
(active: vehicle) to ascending, sequential dose cohorts of SB206.  The highest 
tolerated dose will also be run in a cohort once daily.  Approximately 64 
subjects will be randomized to each cohort (see study schematic). At 
randomization, subjects will be stratified by number of lesions at Baseline (3-
18; 19-70) and atopic dermatitis (AD) history (with AD history vs w/o AD 
history).  A maximum of 16 adult subjects, ages 18 and above,  will be 
randomized into each cohort. 
Subjects will be treated once daily, twice daily or three times a week for up to 
12 weeks to all lesions identified at Baseline and new lesions that arise during 
treatment. If a subject clears all lesions (confirmed by the Investigator at the 
next regular scheduled visit), the treatment period will end, and subjects will 
be followed for recurrence/new lesions until Week 12/ Early Termination 
(ET). All QD dosing should be applied in the morning at home or in the clinic.  

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
Confidential
SB206/NVN1000 
Page 14 of 68
All subjects should apply their last dose to accommodate the 1 to 6 hour 
window for blood draws.  The exact time of the last dose preceding any 
scheduled visit will be collected.   Subjects will visit the clinic at Screening, 
Baseline, Week 1, Week 2, Week 4, Week 8, and Week 12. 
After 30 subjects randomized in a cohort have completed 2 weeks of treatment, 
the Data Safety Monitoring Board (DSMB) will review the available 
unblinded safety and tolerability data.  Using predetermined criteria 
documented in the DSMB charter, the DSMB will determine if the data 
supports escalating to the next highest dose for the next cohort or if the data 
shows the dose is not tolerable decreasing to the next lower dose or frequency 
for the next cohort. After 64 subjects are randomized to a cohort, the next 
cohort will be opened. Once a subject is randomized to a cohort, the subject 
will stay in the cohort. If a subject discontinues treatment, the subject will 
continue in the study and be followed until Week 12 unless the 
subject/caregiver withdraws consent. 
Primary 
Efficacy 
Endpoint: 
Proportion of subjects achieving complete clearance of all molluscum 
contagiosum at Week 12 (Subjects who achieved complete clearance before 
Week 12 need to maintain complete clearance at Week 12). 
Secondary / 
Exploratory 
Endpoints: 
Secondary Efficacy Endpoints 
•
Proportion of subjects achieving complete clearance of all MC at each
visit
•
Time to complete clearance of all MC
•
Proportion of subjects achieving at least a 75% reduction from baseline
in the number of MC at each visit
•
Mean change from baseline in number of MC at each visit
•
Mean percent change from baseline in number of MC at each visit
Exploratory Endpoints 
•
Proportion of subjects whose lesion count decreases and increases from
baseline at each visit
•
Absolute number of subjects who show new lesions after once
achieving complete clearance at each visit
Safety Endpoints 
•
Tolerability assessment (Investigator, Subject)

16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study  
Confidential
SB206/NVN1000 
Page 15 of 68
 
 
 
• Adverse Events 
Exposure Endpoint 
• Determination of hMAP3 plasma concentration at end of treatment, if 
quantifiable 
 
STUDY SCHEMATIC 
 
*Note: T or NT is decided on a cohort basis, not on a subject level, after 30 subjects have 
completed 2 weeks of treatment.  
 
 
 

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TABLE OF CONTENTS 
CLINICAL PROTOCOL APPROVAL FORM .............................................................2 
RATIONALE FOR AMENDMENT ................................................................................3 
IDENTIFICATION OF CHANGES ................................................................................3 
CONFIDENTIALITY AND INVESTIGATOR’S STATEMENT ..............................12 
STUDY SUMMARY ........................................................................................................13 
STUDY SCHEMATIC ....................................................................................................15 
TABLE OF CONTENTS ................................................................................................16 
List of Figures ...................................................................................................................19 
List of Tables ....................................................................................................................19 
LIST OF ABBREVIATIONS .........................................................................................20 
1 
INTRODUCTION AND RATIONALE .................................................................22 
1.1 
Background ..........................................................................................................22 
1.1.1 
Pharmacokinetics ...........................................................................................23 
1.1.2 
Preclinical Pharmacology ..............................................................................23 
1.1.3 
Potential for Drug-Drug Interactions ..........................................................24 
1.1.4 
Clinical Adverse Event Profile ......................................................................24 
1.1.5 
Elevations in Liver Function Tests ...............................................................25 
1.1.6 
Potential Risk of Testicular Injury ...............................................................25 
1.1.7 
Potential Risk to Fetal Development ............................................................25 
1.2 
Study Rationale ....................................................................................................25 
1.2.1 
Dosing Regimen ..............................................................................................26 
1.2.2 
Dose Selection Rationale................................................................................26 
2 
STUDY OBJECTIVES ............................................................................................27 
3 
STUDY ENDPOINTS ..............................................................................................28 
3.1 
Primary Efficacy Endpoint .................................................................................28 
3.2 
Secondary Efficacy Endpoints ............................................................................28 
3.3 
Exploratory Endpoints ........................................................................................28 
3.4 
Safety Endpoints ..................................................................................................28 
3.5 
Exposure Endpoint ..............................................................................................28 
4 
STUDY PLAN ...........................................................................................................29 
4.1 
Study Design .........................................................................................................29 
4.2 
Study Schematic ...................................................................................................30 
5 
POPULATION ..........................................................................................................32 
5.1 
Number of Subjects..............................................................................................32 
5.2 
Inclusion Criteria .................................................................................................32 
5.3 
Exclusion Criteria ................................................................................................32 
5.4 
Subject Screening .................................................................................................33 
5.4.1 
Screening Failures ..........................................................................................34 
5.5 
Deviation from Inclusion/Exclusion Criteria ....................................................34 
6 
STUDY CONDUCT..................................................................................................35 
6.1 
General Instructions ............................................................................................35 
6.2 
Study Procedures by Time Point ........................................................................35 
6.2.1 
Screening (Day-28 to Day 1)..........................................................................35 

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6.2.2 
Visit 1/Baseline (Day 1) ..................................................................................35 
6.2.3 
Visit 2/Week 1 (Day 8 ±3) ..............................................................................36 
6.2.4 
Visit 3/Week 2 (Day 15 ±3) ............................................................................37 
6.2.5 
Visit 4/Week 4 (Day 29 ±3) ............................................................................37 
6.2.6 
Visit 5/Week 8 (Day 57 ±3) ............................................................................38 
6.2.7 
Visit 6/Week 12/ET (Day 85 ±7) ...................................................................38 
6.3 
Discontinuation ....................................................................................................39 
6.3.1 
Treatment Discontinuation ...........................................................................39 
6.3.2 
Study Discontinuation ...................................................................................40 
7 
DESCRIPTION OF STUDY PROCEDURES .......................................................41 
7.1 
Efficacy Assessments ...........................................................................................41 
7.1.1 
Molluscum Contagiosum Lesion Counts .....................................................41 
7.2 
Local Tolerability Assessments (Investigator, Subject/Caregiver) .................41 
7.3 
Safety Assessments ...............................................................................................43 
7.3.1 
Physical Exam ................................................................................................43 
7.3.2 
Vital Signs .......................................................................................................43 
7.3.3 
Clinical Laboratory Tests..............................................................................43 
7.3.4 
Pregnancy Testing ..........................................................................................43 
7.4 
Exposure Assessment ...........................................................................................44 
7.5 
Protocol Deviations ..............................................................................................45 
8 
STUDY DRUG MANAGEMENT ...........................................................................46 
8.1 
Description ............................................................................................................46 
8.1.1 
Formulation ....................................................................................................46 
8.1.2 
Storage ............................................................................................................46 
8.2 
Packaging and Shipment .....................................................................................46 
8.3 
Method of Assigning Subjects to Treatment Groups .......................................47 
8.4 
Blinding and Unblinding Treatment Assignment .............................................47 
8.5 
Dose and Administration .....................................................................................48 
8.6 
Accountability ......................................................................................................48 
8.7 
Prohibited Concomitant Therapy ......................................................................48 
8.8 
Compliance ...........................................................................................................49 
9 
ADVERSE EVENTS ................................................................................................50 
9.1 
Documenting Adverse Events .............................................................................50 
9.2 
Assessment of Severity .........................................................................................50 
9.3 
Assessment of Causality ......................................................................................50 
9.4 
Clinical Laboratory Changes ..............................................................................51 
9.5 
Adverse Event Follow-up ....................................................................................51 
9.5.1 
Follow-Up of Non-Serious Adverse Events..................................................51 
9.5.2 
Follow-Up of Post Study Serious Adverse Events .......................................51 
9.6 
Pregnancy .............................................................................................................51 
9.7 
Overdose ...............................................................................................................52 
10 SERIOUS ADVERSE EVENT ................................................................................53 
10.1 
Definition of Serious Adverse Event ..................................................................53 
10.2 
Reporting Serious Adverse Events .....................................................................54 
11 STATISTICS .............................................................................................................55 

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11.1 
General Procedures .............................................................................................55 
11.2 
Sample Size ...........................................................................................................55 
11.3 
Analysis Populations ............................................................................................55 
11.4 
Statistical Methods ...............................................................................................56 
11.4.1 
Demographic and Baseline Characteristics .................................................56 
11.4.2 
Efficacy Analysis ............................................................................................56 
11.4.3 
Analysis of Safety ...........................................................................................57 
11.5 
Analysis of hMAP3 Plasma Concentrations ......................................................58 
11.6 
Interim Analysis ...................................................................................................58 
12 ETHICS AND RESPONSIBILITIES .....................................................................59 
12.1 
Good Clinical Practice .........................................................................................59 
12.2 
Data Safety Monitoring Board ...........................................................................59 
12.3 
Institutional Review Board/Independent Ethics Committee ...........................59 
12.4 
Informed Consent ................................................................................................59 
12.5 
Records Management ..........................................................................................60 
12.6 
Source Documentation.........................................................................................60 
12.7 
Study Files and Record Retention ......................................................................60 
13 AUDITING AND MONITORING ..........................................................................61 
13.1 
Auditing ................................................................................................................61 
13.2 
Monitoring ............................................................................................................61 
14 AMENDMENTS .......................................................................................................63 
15 STUDY REPORT AND PUBLICATIONS ............................................................64 
16 STUDY DISCONTINUATION ...............................................................................65 
17 CONFIDENTIALITY ..............................................................................................66 
18 REFERENCES .........................................................................................................67 
19 APPENDICES ...........................................................................................................68 
19.1 
APPENDIX I – Names of Study Personnel........................................................68 

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LIST OF FIGURES 
Figure 1:  Ascending Dose Design ..................................................................................30 
 
LIST OF TABLES 
Table 1: Schedule of Assessments ...................................................................................31 
 
 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
AD 
Atopic Dermatitis 
BID 
Twice Daily 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
DSMB 
Data and Safety Monitoring Board 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
mITT 
Modified Intent-to-Treat 
hMAP3 
Hydrolyzed N-Methylaminopropyl-trimethoxysilane 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine Device 
IWRS 
Interactive Web Response System 
MC 
Molluscum Contagiosum 
MedDRA 
Medical Dictionary of Regulatory Affairs 
NOVAN 
Novan, Inc 

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PP 
Per-Protocol Population 
QD 
Once Daily 
SAE 
Serious Adverse Event 
SAF 
Safety Population 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-Emergent Adverse Events 
TIW 
Three Times a Week 
UPT 
Urine Pregnancy Test 

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1 INTRODUCTION AND RATIONALE 
1.1 
Background 
Molluscum contagiosum (MC) is a common skin disorder that aﬀects mainly healthy children 
(Dohil et al, 2006). MC has the greatest incidence in individuals aged 1–14 years (Schofield et al, 
2011); prevalence in children is between 5% and 11% (Olsen et al, 2014).  
MC virus is an important human skin pathogen and can cause disﬁgurement and suffering in 
children.  In adults MC is less common and often sexually transmitted. Extensive and persistent 
skin infection with the virus can indicate underlying immunodeﬁciency. MC virus is distinct from 
other poxviruses because of its host and tissue adaptations. It infects only the skin and, rarely, the 
mucous membranes. The virus has developed efficient mechanisms to grow in differentiating 
cells of the human epidermis and is well adapted to human hosts (Chen et al, 2013).  
Extensive and persistent skin infection with the virus can indicate underlying immunodeficiency. 
Patients with atopic dermatitis have an impaired skin barrier in addition to immunological changes 
which could explain the rising prevalence and high number of lesions in this population. Topical 
corticosteroids and calcineurin inhibitors (both local immunosuppressants commonly applied to 
the skin in patients with atopic dermatitis) have been implicated as contributing factors in some 
patients (Osio et al, 2011). 
MC is transmitted between human hosts by the infectious matter discharged from the lesions. 
According to a prospective community cohort study (Olsen et al, 2015), the mean time to 
resolution was 13.3 months (SD 8.2). Eighty (30%) of 269 cases had not resolved by 18 months; 
36 (13%) had not resolved by 24 months. Transmission to other children in the household occur 
in 102 (41%) of 250 cases.  
Acidified nitrite was used in a double-blind, group-sequential clinical trial to demonstrate the 
efficacy of nitric oxide donor in treating MC (Ormerod et al, 1999). In the study, subjects 
received either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical 
cream with 5% salicylic acid, omitting sodium nitrite. Completion was defined as 3 months, 
or when the patient was cured or dropped out, if sooner. The study demonstrated that a 75% 
cure rate in the active treatment group and 21% cure with control treatment (P = 0.01). The mean 
time to cure was 1.83 months. Staining of the skin and irritation were frequent side-effects 
but did not prevent successful treatment. 
Novan, Inc. (Novan) is conducting this Phase 2 multi-center, randomized, double-blind, vehicle-
controlled, ascending dose study of SB206 in subjects 2 years of age and older with molluscum 
contagiosum. SB206 is a topical gel, formed by mixing NVN1000 Gel with hydrogel. NVN1000 
Gel contains NVN1000, a nitric oxide-releasing macromolecule containing covalently bound N-
diazeniumdiolate nitric oxide donors; nitric oxide release from the macromolecule is initiated by 
mixing NVN1000 Gel with hydrogel. 
Topical formulations of NVN1000 at concentrations ranging from 1-16% have been studied in 19 
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have been exposed to Vehicle and 2600 exposed to NVN1000. In clinical studies completed to 
date, topical application of NVN1000 has generally been well-tolerated with no safety concerns 
identified. A clinical study involving subjects with psoriasis just completed and one in subjects 
with atopic dermatitis is ongoing.  
1.1.1 
Pharmacokinetics 
The systemic bioavailability of NVN1000 after dermal administration has been investigated in two 
maximum use studies in adults and adolescent subjects with moderate to severe acne vulgaris, and 
no detectable systemic exposure was observed. In adult subjects with moderate to severe acne 
vulgaris (NI-AC101) administration of SB204 8% (NVN1000 Gel 16% co-administered with 
hydrogel) or Vehicle Gel daily for 5 days to the face, chest, back, upper shoulders twice daily 
(BID) (17% BSA) showed no detectable systemic exposure on Day 1 or Day 5 to hMAP3, a silicon 
containing component of the parent compound.  There was no noticeable difference in systemic 
nitrate levels on Day 1 or Day 5 in subjects treated with SB204 or Vehicle Gel and no evidence of 
accumulation. Likewise, in an open-label PK, study (NI-AC103) in adolescents (ages 9-16 years) 
with moderate to severe acne vulgaris topical administration of SB204 4% was applied QD for 
21 days to 17% BSA and again no detectable systemic exposure to hMAP3 and no plasma nitrate 
concentrations outside of normal variability and negligible accumulation of nitrate after 21 days 
of dosing.  
Additionally, in a 4-way, randomized, double-blind, cross-over study examining ECG effects 
following SB204 application (NI-AC104), there was no detectable systemic exposure to hMAP3 
and no difference in plasma nitrate levels in 48 subjects with moderate to severe acne treated with 
SB204 (NVN1000) Gel 4%, SB204 (NVN1000) Gel 12% or Vehicle Gel applied to 17% BSA.  
No changes in ECG were observed with therapeutic or supratherapeutic doses of SB204. 
In the recently completed study in subjects with psoriasis (NI-PS101) who were administered a 
cream formulation, SB414 6% (NVN1000 Ointment 12% co-administered with hydrogel),  6 of 
23 subjects (26.0%) had at least one quantifiable hMAP3 plasma concentration following dosing. 
The mean (SD) Cmax of hMAP3 (18.89 [15.02] ng/mL) occurred at 1 hour postdose in the 6 
subjects with quantifiable hMAP3 plasma concentrations. The plasma concentration gradually 
decreased after the peak and hMAP3 was below the the lower limit of quantitation (LLOQ)  in all 
subjects at 12 hours postdose. Systemic exposure to the investigational product was negligible in 
the study. The clinical study report is under preparation. Analyses are currently ongoing to 
determine systemic exposure in a study of subjects with atopic dermatitis (NI-AD101) 
administered SB414 2% (NVN1000 Ointment 4% co-administered with buffered hydrogel) or 6% 
(NVN1000 Ointment 12% co-administed with buffered hydrogel).  
1.1.2 
Preclinical Pharmacology 
During the development of SB204 (NVN1000 Gel) for acne, SB206 (NVN1000 Gel) for the 
treatment of external genital warts and perianal warts, SB208 (NVN1000 Gel) for tinea pedis and 
SB414 (NVN1000 Ointment), Novan has conducted over 90 nonclinical studies. With SB206, 
Novan completed a 4-week daily dosing with 2-week recovery GLP dermal bridging study in 
miniature swine. Under the conditions of this study, the No Observed Adverse Effect Level 

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(NOAEL) was considered to be greater than the nominal dose level evaluated (48 mg/kg/day 
NVN1000), administered as twice daily 8% SB206 Gel or once daily 16% SB206 Gel.  There were 
no meaningful effects on mortality/moribundity, clinical observations, physical examination 
findings, food consumption, weekly body weight or weekly body weight change, clinical 
pathology parameters, ophthalmologic or electrocardiographic examinations, or organ weight 
findings.  Microscopic changes, limited to the superficial dermis and epidermis, were minimal to 
mild but had not completely resolved following the 2-week recovery period. The induced changes 
included hyperkeratosis, epidermal hyperplasia and mononuclear dermal inflammation 
(mononuclear cell infiltration and dermal edema). There was no evidence of systemic nitric oxide 
or hMAP3 exposure at any of the dose levels tested. This study with SB206 Gel in miniature swine 
was successful in bridging the safety of topical administration of NVN1000 in the SB204 
formulation with the SB206 formulation. 
For additional information refer to the Investigator’s Brochure (IB). 
1.1.3 
Potential for Drug-Drug Interactions 
Due to the low systemic exposure observed to date with SB204 clinically and with SB206 
nonclinically the risk of drug-drug interactions is low. 
1.1.4 
Clinical Adverse Event Profile 
Topical formulations of NVN1000 at concentrations ranging from 1-16% have been studied in 19 
completed studies. Over 1900 healthy volunteers or subjects with acne, genital warts or tinea pedis 
have been exposed to Vehicle and 2600 exposed to NVN1000.  
Novan has completed a Phase 2 ascending dose study assessing the tolerability, safety, and efficacy 
of SB206 in subjects with external genital warts (EGW) and perianal warts (PAW). In this study, 
there were no safety concerns with single daily dose application; twice daily application of SB206 
to the genitalia was associated with local application site reactions in some subjects which led to 
treatment discontinuation. The results of this study are supportive of the continued clinical 
development of SB206. 
SB204 is in development for the treatment of acne vulgaris. The acne clinical program for SB204 
includes nine completed Phase 1 studies in healthy volunteers or subjects with acne vulgaris, three 
completed Phase 2 studies, and the completed Phase 3 program (two 12-week placebo-controlled 
studies and one 40-week open label long-term safety study in subjects ages 9 years old and older). 
Based on the clinical data acquired to date, topical application of NVN1000 to healthy volunteers 
or subjects with acne vulgaris has generally been well-tolerated with no safety concerns identified. 
Novan has also completed a study in subjects with tinea pedis using SB208. There were no safety 
concerns identified with once daily dosing to one or both feet; there were no application site 
adverse events reported. 
In completed studies, no clinically significant changes have been observed in laboratory 
assessments, including methemoglobin, in subjects treated with topical NVN1000.  The percent 

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methemoglobin in blood has been measured using pulse co-oximetry in the Phase 1 and Phase 2 
studies in the acne, external genital wart, and anti-fungal programs.  There have been no reports 
of methemoglobinemia or observed methemoglobin levels greater than 3% in subjects treated with 
topical NVN1000 in completed studies. Fluctuations in methemoglobin during treatment have 
been similar in subjects treated with topical NVN1000 or Vehicle.  There have been no clinically 
significant changes in physical examination, including vital signs, in subjects treated with topical 
NVN1000. 
1.1.5 
Elevations in Liver Function Tests 
No clinically significant changes have been observed in laboratory assessments. 
1.1.6 
Potential Risk of Testicular Injury 
In a nonclinical GLP study of fertility and early embryonic development in rats after daily oral 
administration of NVN1000 there was no adverse findings in male fertility parameters or 
reproductive parameters in either sex. 
Additionally, due to the lack of systemic exposure after dermal administration of SB204 clinically 
and SB206 nonclinically observed to date, the risk of testicular injury is low. 
1.1.7 
Potential Risk to Fetal Development 
Oral administration of NVN1000 drug substance in GLP embryo-fetal developmental toxicity 
studies in rats and rabbits showed minor effects on fetal development only at the highest doses. 
Additionally, due to the lack of systemic exposure after dermal administration of SB204 clinically 
and SB206 nonclinically observed to date, the risk to fetal development is low. 
In prior studies using NVN1000 in different diseases, there have been 6 reported pregnancies, of 
those, two were completed to term with healthy babies. One woman had an elective termination 
of her pregnancy and one woman had a miscarriage. The outcome of the other two pregnancies is 
unknown.  
1.2 
Study Rationale 
MC is benign and generally self-limiting. The average duration of a single lesion is about 2 months; 
however, since the lesions spread easily by autoinoculation from scratching or trauma, the mean 
duration of infection is often more than a year. 
Nitric oxide, an endogenous small molecule, provides localized immunity against foreign 
organisms by acting both as a short lived immune modulator and a direct broad-spectrum 
antimicrobial agent.  Topical exogenous nitric oxide has been investigated as an antimicrobial 
agent due to its broad-spectrum activity, ability to inhibit viral replication, and the ability to readily 
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There is a significant unmet medical need to treat MC, considering most patients with MC are 
healthy young children. Ablative treatment often causes fear to the children and interfere in 
physician-patient relationships. Repeated ablative treatment become difficult. Using anesthesia 
involves safety risk and costs. Not treating increases further dissemination of the disease. Topical 
application of SB206 which releases nitric oxide may accelerate resolution of MC without causing 
pain, and provide an effective, convenient treatment option of MC. Prevention of further 
dissemination of the disease is also important from public health perspective. 
1.2.1 
Dosing Regimen 
A thin layer of SB206 4%, SB206 8%, SB206 12% or Vehicle Gel will be applied once daily, 
twice daily, or three times a week depending on the assigned cohort, to all affected areas of MC 
for 12 consecutive weeks (84 days). Subjects/caregivers will apply the study drug to all lesions 
identified at Baseline and new lesions that arise during treatment. If a subject clears all lesions 
(confirmed by the Investigator at the next regular scheduled visit), the treatment period will end 
and subjects will be followed for recurrence/new lesions until Week 12/ET.  
All QD dosing should be applied in the morning at home or in the clinic.  All subjects should apply 
their last dose to accommodate the 1to 6 hour window for blood draws.   The exact time of the last 
dose preceding any scheduled visit will be collected. Each dose will consist of NVN1000 Gel or 
Vehicle Gel with an equal volume of hydrogel mixed thoroughly together by the subject or 
caregiver and applied to the lesions and approximately 1 cm surrounding each lesion.  Periocular 
lesions will be treated if the lesions are at least 2 cm from the edge of the eye.  Lesions on the labia 
and penis will not be treated. 
Study personnel will ensure that the subjects or caregivers can identify the treatment area(s) and 
know where to apply the study drug. Subjects will be instructed on the correct use of study drug 
and the amount to apply during Baseline/Day 1 according to the corresponding subject instructions 
for use that will be provided to the subject. 
1.2.2 
Dose Selection Rationale 
Based on the previous nonclinical and clinical safety profiles of NVN1000 topical formulations 
and a nonclinical NOAEL approximately 1.8 fold higher than the highest dose of SB206 to be 
applied in this study, these doses are expected to be safe and well tolerated.  

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2 STUDY OBJECTIVES 
• To evaluate the efficacy of SB206 over vehicle gel for up to 12 weeks of topical treatment 
of MC 
• To evaluate the safety and tolerability of SB206 for up to 12 weeks treatment of MC  
• To evaluate and determine a safe and efficacious SB206 dose level for future studies 
 

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3 STUDY ENDPOINTS  
The following endpoints will be assessed during the study. 
3.1 
Primary Efficacy Endpoint 
• Proportion of subjects achieving complete clearance of all MC at Week 12 (Subjects who 
achieved complete clearance before Week 12 need to maintain complete clearance at Week 
12) 
3.2 
Secondary Efficacy Endpoints 
• Proportion of subjects achieving complete clearance of all MC at each visit 
• Time to complete clearance of all MC 
• Proportion of subjects achieving at least a 75% reduction from baseline in number of MC 
at each visit 
• Mean change from baseline in number of MC at each visit 
• Mean percent change from baseline in number of MC at each visit 
3.3 
Exploratory Endpoints 
• Proportion of subjects whose lesion count decreases and increases from baseline at each 
visit 
• Absolute number of subjects who show new lesions after once achieving complete 
clearance at each visit 
3.4 
Safety Endpoints 
Safety assessments will be performed at scheduled timepoints throughout the study and include 
physical examination, vital signs, standard clinical laboratory testing (hematology, serum 
chemistry), methemoglobin measurement, pregnancy test, tolerability evaluation, concomitant 
medications, and adverse events. 
3.5 
Exposure Endpoint 
Blood for determination of the hMAP3 plasma concentration will be collected at a single time 
point at the end of treatment to evaluate if quantifiable concentrations can be measured following 
repeated application. 
 

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4 STUDY PLAN 
4.1 
Study Design 
This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled ascending dose 
study to be conducted in up to approximately 192 or 256 non-immunocompromised subjects 
with MC. After obtaining informed consent, subjects who satisfy entry criteria will be 
randomized 3:1 (active: vehicle) to ascending, sequential dose cohorts of SB206.  The highest 
tolerated dose will also be run in a cohort once daily.  Approximately 64 subjects will be 
randomized to each cohort (see study schematic). At randomization, subjects will be stratified 
by number of lesions at Baseline (3-18; 19-70) and atopic dermatitis (AD) history (with AD 
history vs w/o AD history).  A maximum of 16 adult subjects, ages 18 and above, will be 
randomized into each cohort. 
Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks to all 
lesions identified at Baseline and new lesions that arise during treatment. If a subject clears all 
lesions (confirmed by the Investigator at the next regular scheduled visit), the treatment period 
will end, and subjects will be followed for recurrence/new lesions until Week 12/ET.  All QD 
dosing should be applied in the morning at home or in the clinic.  All subjects should apply their 
last dose to accommodate the 1 to 6 hour window for blood draws.   The exact time of the last 
dose preceding any scheduled visit will be collected. Subjects will visit the clinic at Screening, 
Baseline, Week 1, Week 2, Week 4, Week 8, and Week 12/ET.  
After 30 subjects randomized in a cohort have completed 2 weeks of treatment, the DSMB will 
review the available unblinded safety (Methemoglobin, AE, SAE) and tolerability data.  Using 
predetermined criteria documented in the DSMB charter, the DSMB will determine if the data 
supports escalating to the next highest dose for the next cohort or if the data shows the dose is 
not tolerable, decreasing to the next lower dose or frequency for the next cohort. After 64 
subjects are randomized to a cohort, the next cohort will be opened. Once a subject is randomized 
to a cohort, the subject will stay in the cohort. If a subject discontinues treatment, the subject 
will continue in the study and be followed until Week 12 unless the subject/caregiver withdraws 
the consent. 
The standard operating procedures of the DSMB will be documented in the DSMB charter, 
including the board’s accountability to Novan.       

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4.2 
Study Schematic 
Figure 1:  Ascending Dose Design 
Once a subject is randomized to a cohort, the subject will stay in the assigned cohort. 
 
*Note:  T or NT is decided on a cohort basis, not on a subject level, after 30 subjects have 
completed 2 weeks of treatment. 
 

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Table 1: Schedule of Assessments 
1 Screening and Baseline may occur on the same day. 
2 All visit dates are in reference to Baseline, e.g. Week 1 occurs 7 days after Baseline Visit. 
3 Collected at the last day of treatment. 
4 Collected via pulse co-oximetry at site. 
5 Blood for determination of the hMAP3 plasma concentration will be collected at a single time approximately 1 to 6 hours following last dose application.  The 
time of the sample collection and the time of last dose preceding the scheduled visit will be recorded.  The blood sample may be collected at the same time as 
the chemistry and hematology sample. 
6Selected sites and subjects. 
7 Females 10 years of age and older. Subjects whose Baseline is within 7 days of Screening do not require UPT retesting. 
  
Screening1 
(Day -28 to 
Day 1) 
Visit 11 
Baseline 
(Day 1) 
Visit 22 
Week 1 
(Day 8 ±3) 
Visit 32 
Week 2 
(Day 15 ±3) 
Visit 42 
Week 4 
(Day 29 ±3) 
Visit 52 
Week 8 
(Day 57 ±3) 
Visit 62 
Week 12/ET 
(Day 85 ±7) 
Informed Consent (Assent) 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
X 
 
 
 
 
 
Lesion Counts 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
  
X 
 
  
  
  
 X 
Vital Signs 
  
X 
X 
X 
X 
X 
X 
Chemistry & Hematology3 
 
X 
 
  
  
  
 X 
Methemoglobin4 
  
X 
X 
X 
X 
X 
X 
Assessment of hMAP3 plasma concentration5,6 
 
 
 
 
 
 
X 
Urine Pregnancy Test7 
X 
X 
 
  
X 
X 
X 
Tolerability Evaluation 
  
X 
X 
X 
X 
X 
X 
Photographs6 
  
X 
 
 
X 
 
X 
In Clinic Study Drug Application and Provide 
Subject Instructions 
 
X 
 
 
 
 
 
Dispense Subject Diary 
 
X 
 
 
X 
X 
 
Review Study Compliance 
 
 
X 
X 
X 
X 
X 
Collect Subject Diary 
 
 
 
 
X 
X 
X 
Drug Dispensed 
 
X 
 
 
X 
X 
 
Collect Study Drug 
 
 
 
 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Review Concomitant Medications and 
Adverse Events  
 
X 
X 
X 
X 
X 
X 

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5 POPULATION 
5.1 
Number of Subjects 
Up to approximately 192 males and females, 2 years of age and older, with a minimum of 3 and a 
maximum of 70 lesions of MC at baseline will be randomized across a minimum of 3 cohorts. If 
the third cohort is administered 12% BID then up to an additional 64 subjects will be randomized 
in a fourth cohort (see Figure 1). 
5.2 
Inclusion Criteria 
1. Be 2 years of age or older, and in good general health; 
2. Have a signed written informed consent form by a parent or legal guardian (assent form 
where required);  
3. Have between 3 and 70 MC at baseline, excluding periocular (within 2 cm circumference 
of the eye) and lesions on the labia and penis; 
4. Females 10 years of age and older must have a negative urine pregnancy test (UPT) prior 
to randomization; 
5. Females 10 years of age and older must agree to use an effective method of birth control 
during the course of the study and for 30 days after their final study visit; 
6. Be willing and able to follow study instructions and likely to complete all study 
requirements. 
5.3 
Exclusion Criteria 
1. Are immunosuppressed (e.g. HIV, cancer or solid organ transplant), have immunodeficiency 
disorder, or are on immunosuppressive treatment; 
2. Have agminated MC that could make it difficult to provide accurate lesion counts; 
3. Have active atopic dermatitis with intense erythema and/or excoriations that impact currently 
or could impact at any point during the study the ability to count MC lesions;  
Note: History of atopic dermatitis is not an exclusion but will be captured and used for 
stratification. Diagnosis of atopic dermatitis for this study purpose can be based on the 2 
essential features (Eichenfield, 2014): Pruritus and Eczema (acute, subacute, chronic) 
with typical morphology and age-specific patterns* and chronic or relapsing history. 
 
 

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*Patterns include: 
− Facial, neck, and extensor involvement in infants and children 
− Current or previous flexural lesions in any age group 
− Sparing of the groin and axillary regions 
4. Have significant eczematous reactions or other skin disease surrounding MC that may 
impact ability to count lesions; 
5. Have received treatment with topical calcineurin inhibitors or steroids on MC or within 2 
cm of MC lesions within 14 days prior to baseline; 
6. Have received treatment for MC during the 14 days prior to baseline with 
podophyllotoxin, imiquimod, cantharidin, sinecatechins, topical retinoids, oral or topical 
zinc, or other homeopathic or OTC products including, but not limited to, Zymaderm and 
tea tree oil, cimetidine and other histamine H2 receptor antagonists;  
7. Have received surgical procedures (cryotherapy, curettage, other) within 28 days prior to 
Baseline; 
8. Have MC only in periocular area; 
9. Have MC only on the labia or penis; 
10. Female subjects who are pregnant, planning a pregnancy or breastfeeding; 
11. Have a confirmed methemoglobin level of > 3.0% at Baseline using a pulse co-oximeter; 
12. Have known hypersensitivity to any ingredients of SB206 or Vehicle Gel including 
excipients; 
13. Have participated in a previous study with NVN1000; 
14. Have participated in any other trial of an interventional investigational drug or device 
within 30 days or 5 half-lives (whichever is longer) or concurrent participation in another 
interventional research study. 
5.4 
Subject Screening 
Written informed consent (assent form where required) will be obtained before any study-related 
procedures are performed. The Investigator may discuss the study and the possibility for entry with 
a potential subject without first obtaining consent. A subject wishing to participate must give 
written informed consent/assent prior to any study-related procedures being conducted, including 
those performed solely for the purpose of determining eligibility for study participation or 
withdrawal from current medication (if required prior to study entry). The Investigator has both 

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the ethical and legal responsibility to ensure that each subject being considered for inclusion in 
this study has been given a full explanation of the procedures and expectations for study 
participation.  
The site-specific informed consent forms (ICF)/assent forms must be forwarded to the clinical 
research organization (CRO) for approval prior to submission to an Institutional Review Board 
(IRB) as appropriate. Each subject will sign the ICF that has been approved by the same IRB 
responsible for protocol approval. Each ICF/assent form must adhere to the ethical principles 
stated in the Declaration of Helsinki and will include the elements required by Food and Drug 
Administration (FDA) regulations in 21 CFR as well as the International Conference on 
Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, and applicable federal and local 
regulatory requirements. The ICF/assent form(s) must also include a statement that Novan and the 
CRO (or their designees) and auditing regulatory agencies will have direct access to the subject’s 
records and medical history.  
Once the appropriate essential information has been provided to the subject/caregiver and fully 
explained by the Investigator (or a qualified designee) and it is felt that the subject/caregiver 
understands the implications and risks of participating in the study, the IRB approved ICF/assent 
document shall be signed and dated by both the subject/caregiver and the person obtaining consent 
(Investigator or designee), and by any other parties required by the IRB or other regulatory 
authorities. The subject/caregiver will be given a copy of the signed ICF/assent document with the 
original kept on file by the Investigator. All of the above activities must be completed before any 
study related procedures are conducted. 
5.4.1 
Screening Failures 
A subject is considered screened once they have a signed ICF/assent and completed one screening 
assessment. A screen failure subject will be any screened subject who does not get randomized to 
a treatment arm. Subjects will be allowed to rescreen. 
5.5 
Deviation from Inclusion/Exclusion Criteria 
Deviation from the Inclusion/Exclusion Criteria is not allowed. Any deviation identified during 
the study should be discussed with the CRO and/or Novan. 
 

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6 STUDY CONDUCT 
6.1 
General Instructions 
Prospective subjects as defined by the eligibility criteria (Inclusion/Exclusion Criteria) will be 
considered for entry into this study. Subjects’ ICF/assent must be obtained prior to conducting any 
procedures. Some Baseline procedures (i.e., review of inclusion/exclusion criteria, brief physical 
exam, blood pressure and pulse rate, methemoglobin assessment, adverse event assessment, 
concomitant medication review, and UPT) must be completed prior to randomization. Subjects 
who meet all eligibility criteria who do not require washout from any current treatment may be 
screened and randomized on the same day. 
After the required procedures are completed and study eligibility is confirmed, the subject will be 
randomized to treatment utilizing an Interactive Web Response System (IWRS) which will 
identify the study drug to be dispensed to the subject. The subject/caregiver will be trained on the 
mixing, application, and storage of the study drug. The first application should be done at the 
clinic. 
6.2 
Study Procedures by Time Point 
6.2.1 
Screening (Day-28 to Day 1)  
The following procedures must be performed and recorded at the Screening visit: 
1. Review study procedures and information regarding the study including the potential risk 
and benefits of SB206 with the subject/caregiver and obtain written ICF/assent. 
2. Obtain demographic information. 
3. Obtain subject’s medical history (including start date of the subject’s current episode of 
molluscum (i.e., when molluscum was first noticed by the subject/caregiver)), medication 
history and concomitant medication information. 
4. Obtain urine pregnancy test and evaluate results.  If pregnancy test is positive, the subject 
may not participate in the study. 
5. Perform lesion counts. 
6.2.2 
Visit 1/Baseline (Day 1) 
The following procedures must be performed and recorded at the Baseline visit. 
1. Update medication history and concomitant medication information. 
2. Perform lesion counts. 
3. Collect vital signs. 

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4. Perform a brief physical examination. 
5. Collect blood samples for chemistry and hematology. 
6. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
7. Obtain urine pregnancy test.  If pregnancy test is positive, the subject may not participate 
in the study. 
8. Selected sites obtain photographs of all areas where lesions appear (only areas that have at 
least 3 lesions). 
9. Confirm eligibility and randomize subject. 
10. Dispense subject diary and study drug. Weigh and record study product tubes. Instruct 
subject on dispensing, mixing, and application of study product and diary completion. 
11. Have subject/caregiver apply first dose in clinic. 
12. Perform tolerability assessments 30 minutes post dose. 
13. Collect and record AE information for AEs reported. 
6.2.3 
Visit 2/Week 1 (Day 8 ±3) 
The following procedures must be performed and recorded at the Week 1 visit. 
1. Update concomitant medication information. 
2. Perform lesion counts. 
3. Collect vital signs. 
4. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
5. Perform tolerability assessments. 
6. Review study compliance. 
7. Collect and record AE information for AEs reported. 
 
 

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6.2.4 
Visit 3/Week 2 (Day 15 ±3) 
The following procedures must be performed and recorded at the Week 2 visit. 
1. Update concomitant medication information. 
2. Perform lesion counts. 
3. Collect vital signs. 
4. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
5. Perform tolerability assessments. 
6. If subject discontinues treatment, collect blood samples for chemistry, hematology and 
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
7. Review study compliance. 
8. Collect and record AE information for AEs reported. 
6.2.5 
Visit 4/Week 4 (Day 29 ±3) 
The following procedures must be performed and recorded at the Week 4 visit. 
1. Update concomitant medication information. 
2. Perform lesion counts. 
3. Collect vital signs. 
4. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
5. Obtain pregnancy test and evaluate results.  If pregnancy test is positive, the subject may 
not continue in the study. 
6. Perform tolerability assessments. 
7. If subject discontinues treatment, collect blood samples for chemistry, hematology and 
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
8. Selected sites obtain photographs of all areas where Baseline photographs were collected. 
9. Collect subject diaries and returned study medication. Weigh and record study product 
tubes. Review study compliance. 

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10. Weigh, record and dispense new supply of study product and dispense subject diary. 
11. Collect and record AE information for AEs reported. 
6.2.6 
Visit 5/Week 8 (Day 57 ±3) 
The following procedures must be performed and recorded at the Week 8 visit. 
1. Update concomitant medication information. 
2. Perform lesion counts. 
3. Collect vital signs. 
4. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
5. Perform tolerability assessment. 
6. If subject discontinues treatment, collect blood samples for chemistry, hematology and 
hMAP3 and confirm time of last dose with subject/caregiver or apply dose in clinic. 
7. Collect subject diaries and returned study medication. Weigh and record study product 
tubes. Review study compliance. 
8. Weigh, record and dispense new supply of study product and dispense subject diary. 
9. Collect and record AE information for AEs reported. 
6.2.7 
Visit 6/Week 12/ET (Day 85 ±7) 
The following procedures must be performed and recorded at the Week 12/ET visit. 
1. Update concomitant medication information. 
2. Perform a brief physical exam. 
3. If subject is still on treatment, collect blood samples for chemistry, hematology and hMAP3 
and confirm time of last dose with subject/caregiver or apply dose in clinic. 
4. Perform lesion counts. 
5. Collect vital signs. 
6. Measure percent methemoglobin using Masimo handheld pulse co-oximeter device and 
instructions provided by Novan. 
7. Obtain pregnancy test and evaluate results.  

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8. Perform tolerability assessments. 
9. Select sites obtain photographs of all areas where Baseline photographs were collected. 
10. Collect subject diaries and returned study medication. Weigh and record study product 
tubes. Review study compliance. 
11. Collect and record AE information for AEs reported. 
6.3 
Discontinuation 
6.3.1 
Treatment Discontinuation 
If at any time during the study the Investigator determines that it is not in the best interest of the 
subject to continue treatment, the subject’s treatment will be discontinued. The Investigator can 
discontinue the treatment for a subject at any time if medically necessary. If a subject’s treatment 
is discontinued by the Investigator because of an AE, that AE should be indicated as the reason for 
treatment discontinuation.  In this case, the subject is discontinued from the treatment, but still 
participates in the study and is encouraged to follow the visit schedule and complete all 
assessments.  
The Investigator may discontinue a subject’s treatment if the subject/caregiver has failed to follow 
study procedures or to keep follow-up appointments. Appropriate documentation in the subject’s 
study record and the study database regarding the reason for treatment discontinuation must be 
completed. 
Reasons for an Investigator’s withdrawal of a subject from the treatment may include, but are 
not limited to, the following: 
• Safety (e.g., severe adverse reactions, pregnancy) 
• When a concomitant medication or treatment likely to interfere with the results of the study 
is reported, or required, by the subject (the Investigator will decide, in consultation with 
the CRO whether the subject is to be withdrawn) 
Reason(s) for discontinuation from the treatment as listed in the study record will be entered into 
the study database as follows: 
• Completed (due to clearance of all MC or 12 weeks of treatment) 
• Adverse Event 
• Withdrawal by Subject/caregiver 
• Physician Decision 
• Protocol Violation 

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• Lost to Follow-Up 
• Pregnancy 
• Lack of Efficacy 
• Other 
6.3.2 
Study Discontinuation 
A subject/caregiver may voluntarily withdraw from study participation at any time. If the 
subject/caregiver withdraws consent and discontinues from the study, the Investigator will attempt 
to determine the reason for discontinuation and record the reason in the subject’s study records 
and in the study database. In the event of discontinuation from the study, (i.e., prior to Week 12/ET) 
every effort should be made to have the subject return to the study center to complete the Week 
12/ET evaluations. Subjects who withdraw from the study will not be replaced. 
All subjects who fail to return to the study center will be contacted by telephone to determine the 
reason(s) why the subject failed to return for the necessary visit or elected to discontinue from the 
study. If a subject/caregiver is unreachable by telephone after a minimum of two documented 
attempts (one attempt on two different days), a certified letter will be sent requesting that the 
subject contacts the Investigator. These actions will be reported on the subject’s study record and 
a copy of the follow-up letter maintained in the Investigator's file. 
An Investigator may withdraw a subject from the study when a subject is lost to follow-up.   
All premature discontinuations and their causes must be carefully documented by the Investigator 
on the subject’s study record and in the study database. 
All Week 12/ET evaluations should be performed at the time of premature discontinuation. All 
data gathered on the subject prior to termination will be made available to the CRO. 
Study completion or reason(s) for discontinuation from the study as listed in the study record will 
be entered into the study database as follows: 
• Completed 
• Withdrawal by Subject/caregiver 
• Lost to Follow-Up 
Novan has the right to terminate or stop the study at any time. Should this be necessary, the 
Investigator will ensure that proper study discontinuation procedures are completed. 

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7 DESCRIPTION OF STUDY PROCEDURES 
Study procedures and their timings are summarized in the Schedule of Assessments (refer to Table 
1). 
7.1 
Efficacy Assessments 
7.1.1 
Molluscum Contagiosum Lesion Counts 
Molluscum contagiosum is a viral infection characterized by small, discrete, waxy, skin-colored, 
dome-shaped papules, an average of 3–5 mm in diameter. The papules may be umbilicated and 
contain a caseous plug. When the lesions are squeezed or traumatized, a creamy, grey-white 
material can be extruded. 
For this clinical trial purpose, only active MC lesions are counted. Active MC lesions are dome-
shaped, pearly and shiny white top centered papules.  They may have a central dimple 
(umbilication). In order to correctly diagnose, the evaluator should confirm the papular nature of 
molluscum by touching and feeling and using a magnifier, if necessary. Training on how to 
accurately count the number of MC lesions will be provided.  
Definition of Clearance: “Clear” means, in the study, resolution of the active molluscum lesion 
with dome-shaped, pearly and shiny white top centered papule, with or without umbilication. After 
resolution, the residual surface changes such as pitting, scar, and hyper/hypo pigmentation may 
remain.  These signs should not be counted as active lesions. Inflammatory reaction may also occur 
during the natural healing process. Refer to the lesion count training for details. 
The same blinded evaluator should perform lesion counts at Screening, Baseline, and Weeks 1, 2, 
4, 8 and 12/ET. In the event that this is not possible due to unforeseen circumstances, a different 
blinded evaluator may evaluate the subject. However, the same evaluator should evaluate subjects 
at the Baseline and Week 12/ET evaluations.  
Periocular lesions that are not treated will not be included in the lesion count. Lesions on the labia 
and penis will not be treated and will not be included in the lesion count. 
7.2 
Local Tolerability Assessments (Investigator, Subject/Caregiver) 
Inflammatory reaction around the MC is considered as a predictor of imminent resolution of MC 
(beginning-of-the-end sign, BOTE sign). The Investigator needs to carefully assess and if possible, 
differentiate the irritation symptom and sign (tolerability) from the BOTE sign (Butala, 2013). 
Subjects will be assessed at each visit from Baseline through Week 12/ET for local tolerability. At 
Baseline, the subject must remain at least 30 minutes after the initial application of study product 
for the local tolerability assessments. The Investigator (or designated evaluator) will assess the 
presence and overall degree of irritation (dryness, erythema, and peeling) at the application sites 
and the score will reflect what the investigator/evaluator sees at the time of the assessment. The 
score will ideally represent an “average” across all application sites. To the fullest extent possible 

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the same investigator (or designated evaluator) will perform all tolerability assessments for an 
individual subject throughout the study. Scores of 3 or 4 (Severe or Very Severe) should be 
reported as an AE. The score will be a global assessment based on all parameters.  There will not 
be a unique score for each parameter.  
Investigator Assessment of Dryness, Erythema, and Peeling 
Score Severity 
Description 
0 
No irritation 
No evidence of local irritation/intolerance 
1 
Mild 
Minimal erythema and/or edema, slight glazed appearance 
2 
Moderate 
Definite erythema and/or edema with peeling and/or cracking but does not 
require treatment modification 
3 
Severe (report as 
an AE) 
Erythema, edema glazing with fissures, few vesicles or papules 
4 
Very severe 
(report as an AE) 
Strong reaction spreading beyond the treated area, bullous reaction, erosions 
At Baseline and all post baseline visits, subjects will use a 5-point tolerability scale to assess the 
presence and degree of burning/stinging and itching. 
At the Baseline visit, 30 minutes post-dose, the subject will be asked to rate the overall severity of 
their itching and burning/stinging. The assessment will apply only to the time since application of 
study drug. At Week 1 through Week 12/ET the subject will be asked to rate the overall severity 
of their itching and burning/stinging at the treatment areas since their previous visit. The score will 
ideally represent an “average” across all application sites. The subject’s caregiver can assist in 
providing a score as needed. If the subject reports scores of 4 (Strong/Severe) at any visit, the 
investigator should assess for accompanying signs and symptoms (erythema, edema, vesicles, 
papules, or erosions, etc.) and report as an AE accordingly. The following scores, severity and 
descriptions will be used to score subject reported tolerability. There will be one score based on a 
full assessment of both burning/stinging and itching. There will not be a unique score for each 
parameter. 
Subject Assessment of Burning/Stinging and Itching 
Score 
Severity 
Description 
0 
None 
Normal, no discomfort 
1 
Slight 
An awareness, but no discomfort and no intervention required 
2 
Mild 
A noticeable discomfort that causes intermittent awareness 
3 
Moderate 
A noticeable discomfort that causes intermittent awareness and 
interferes occasionally with normal daily activities 
4 
Strong/Severe A definite continuous discomfort that interferes with normal daily 
activities 

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7.3 
Safety Assessments 
7.3.1 
Physical Exam 
A brief physical examination will include heart, lung, and abdomen evaluation. This physical 
examination will be performed at Baseline and at Week 12/ET. Height and weight will only be 
collected at Baseline. Any clinically significant changes in the physical exam from baseline will 
be recorded as AEs. 
7.3.2 
Vital Signs 
Blood pressure and pulse rate will be collected at  Baseline, Week 1, Week 2, Week 4, Week 8 
and Week 12/ET. Any clinically significant changes in vital signs from baseline will be recorded 
as AEs. 
7.3.3 
Clinical Laboratory Tests 
Chemistry and hematology will be collected at Baseline and on the last day of treatment.  Clinically 
significant changes in laboratory values will be recorded as AEs. 
Methemoglobin will be measured at Baseline, Weeks 1, 2, 4, 8 and Week 12/ET using a Masimo 
Rainbow® SET® Rad-57™ pulse co-oximeter. The percent methemoglobin will be displayed on 
the pulse co-oximeter and recorded in the subject’s source documents and in the case report form 
(CRF). Subjects with methemoglobin greater than 3.0% at baseline are not eligible for the study. 
Subjects with a confirmed methemoglobin > 5.0% at any post-baseline visit will be discontinued 
from the study. A confirmed methemoglobin is defined as at least 2 readings within 0.5% of each 
other taken within a 30-minute period. Methemoglobin levels will not be collected as AEs; 
however, if a subject has signs/symptoms of methemoglobinemia and an elevated methemoglobin 
level, methemoglobinemia should be reported as an AE. 
7.3.4 
Pregnancy Testing 
Urine pregnancy testing for females 10 years of age and older will be collected at Screening, 
Baseline, Week 4, Week 8 and Week 12/ET. In addition to having a negative UPT at Baseline (and 
Screening unless Visit 1 is within 7 days of Screening) before the first application of study drug, 
females 10 years of age and older must be willing to use an acceptable form of birth control during 
the study. The following are considered acceptable methods of birth control for this study: 
abstinence with a documented acceptable method of birth control if the subject becomes sexually 
active, oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, 
double-barrier methods (e.g., condom and spermicide), contraceptive injection, Intrauterine 
Device (IUD), hormonal IUD, permanent contraception, same sex partner or partner who has had 
a vasectomy. 

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7.4 
Exposure Assessment 
At select sites, a blood sample will be collected at the Week 12 visit from those subjects who have 
not previously discontinued treatment.  The sample will be collected at a single time point 
approximately 1 to 6 hours following application of study drug.  The final dose may be either be 
done at home or in the clinic.  The time of dose application and sample collection should be 
recorded.  Blood may be collected at the same time as the chemistry and hematology sample, but 
the chemistry and hematology samples should be drawn first. If a subject discontinues treatment 
for any reason (e.g., lesion clearance, subject withdrawal, physician decision) before Visit 6, blood 
should be collected on the last day of treatment. 
Instructions for processing and transporting plasma samples for analysis will be described 
separately. 

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7.5 
Protocol Deviations 
This study will be conducted as described in this protocol, except for in emergency situations in 
which the protection, safety, and well-being of the subject requires immediate intervention, based 
on the judgment of the Investigator (or a responsible, appropriately trained professional designated 
by the Investigator). In the event of a significant deviation from the protocol due to an emergency, 
accident, or mistake, the Investigator or designee must contact the CRO at the earliest possible 
time by telephone. This will allow an early joint decision regarding the subject’s continuation in 
the study. This decision will be documented by the Investigator and the CRO. 

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8 STUDY DRUG MANAGEMENT 
8.1 
Description 
8.1.1 
Formulation  
Investigational Drug: SB206 4%, 8% or 12% 
Comparator Drug: Vehicle Gel 
Dosing: Approximately 1.0g of SB206 QD, BID 
or TIW 
Dosing: Approximately 1.0g of Vehicle Gel QD, 
BID or TIW 
8.1.2 
Storage 
Upon receipt from Novan, or Novan’s designee, a study staff member will place all study supplies 
in a refrigerated temperature-controlled and monitored area. The SB206/Vehicle study product 
should be refrigerated (2-8°C/36-46°F) until dispensed. 
Access to study supplies should be strictly limited to the study staff. Neither the Investigator nor 
any member of the study staff will distribute any of the study supplies to any person not 
participating in this study. 
If a study staff member becomes aware that the study supplies have not been properly handled 
(i.e., supply arrives and was not placed in refrigerator upon receipt or there is a temperature 
excursion during shipment), the CRO must be contacted immediately. In such an event, study 
supplies should be quarantined and not be administered to any subject until Novan provides further 
direction. 
It is expected that the site staff will maintain refrigerator temperature logs in the refrigerated study 
drug storage area, recording the temperature at least once each working day. Excursions in 
temperature during storage should be discussed with the CRO immediately and study supplies 
should be quarantined and not administered until Novan provides approval for use. Other supplies 
will be stored at room temperature. 
The study drug will be dispensed at the discretion of and by the direction of the designated study 
personnel in accordance with the conditions specified in this protocol. It is the Investigator’s 
responsibility to ensure that accurate records of study drug dispensing and return are maintained. 
8.2 
Packaging and Shipment 
Novan, or designee, will provide all study drug to the sites. Sites are required to maintain all 
records of shipment and receipt in the Investigator Site File. 
 
 

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8.3 
Method of Assigning Subjects to Treatment Groups 
In this randomized, double-blind, vehicle-controlled study, subjects who meet study entry criteria 
will be randomly assigned in a 3:1 ratio (active: vehicle) to ascending, sequential dose cohorts of 
SB206. The randomization schedule will be computer generated using a permuted block algorithm 
and will randomly allocate IP to randomization numbers. The randomization numbers will be 
assigned sequentially through a central interactive web response system (IWRS) as subjects are 
entered into the study (Cohort 1, then Cohort 2, then Cohort 3). Randomization will be stratified 
by number of lesions at baseline (3-18, 19-70) and atopic dermatitis history (with AD history vs 
w/o AD history).  A maximum of 16 adult subjects, ages 18 and above, will be randomized into 
each cohort. 
8.4 
Blinding and Unblinding Treatment Assignment 
All subjects, investigators, and study personnel involved in the conduct of the study will be blinded 
to treatment assignment, with the exception of a specified unblinded statistician who will generate 
and have access to the randomization code. The unblinded study personnel will not otherwise 
participate in study procedures or data analysis prior to unblinding of the study data to all study 
related personnel.  
 
Several analyses of unblinded data are planned throughout the study.  A Data Safety Monitoring 
Board (DSMB) will conduct an unblinded review of safety and tolerability data after 30 subjects 
are enrolled and treated for two weeks within in each cohort.  After all subjects in Cohort 3 have 
completed their last study visits, the database for all subjects in Cohorts 1-3 will be frozen for 
purposes of an interim analysis of safety and efficacy data.  While this interim analysis is being 
prepared, the study will complete through Cohort 4 and the final analysis will be based on all 
subjects in Cohorts 1-4: Cohort 4 (QD dosing of SB206 8% or 12% vs. vehicle).   Personnel who 
are not otherwise involved in the study will prepare the unblinded data and summary tables for the 
interim analysis.  
Study personnel will endeavor to safeguard the integrity of the study blind to minimize bias in the 
conduct of the study. Individual treatment unblinding is discouraged since knowledge of the 
treatment assignment will not materially change the planned management of a medical emergency. 
Unblinding should be discussed in advance with the medical monitor if possible. Study personnel 
will utilize the IWRS for emergency unblinding. If the investigator is not able to discuss treatment 
unblinding in advance, then he or she must notify the medical monitor as soon as possible about 
the unblinding incident without revealing the subject’s treatment assignment. The investigator or 
designee must record the date and reason for study discontinuation on the appropriate CRF for that 
subject. In all cases that are not emergencies, the investigator must discuss the event with the 
medical monitor prior to unblinding the subject’s treatment assignment.  
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
subject’s treatment assignment is unblinded, he or she may or may not be asked to withdraw from 
the study. The investigator will make this decision after consultation with the medical monitor. 

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8.5 
Dose and Administration 
Subjects will apply treatment once daily, twice daily or three times a week for up to 12 weeks to 
all lesions identified at baseline and new lesions that arise during treatment depending on the 
frequency of the cohort plus the dose selected for the cohort. If a subject clears all lesions 
(confirmed by the Investigator at the next regular scheduled visit), the treatment period will end 
and subjects will be followed for recurrence/new lesions until Week 12/ET.  
An increase in the number of MC lesions (with or without inflammatory reaction) during the early 
phase of the resolution is often observed. It is important to instruct the subject/caregiver to treat 
the new lesions as well as the existing lesions. 
Each dose will consist of NVN1000 Gel or Vehicle Gel with an equal volume of hydrogel 
thoroughly mixed together by the subject or caregiver and applied to the lesions, approximately 1 
cm surrounding each lesion. 
Periocular lesions will be treated if the lesions are at least 2 cm from the edge of the eye.  Lesions 
on the labia and penis will not be treated. 
8.6 
Accountability 
The dispensing and return of all study drug will be recorded on a dispensing log. The subject 
number/initials, and the initials and date of the person dispensing and receiving the returned 
medication will be documented on this form. All study product will be weighed at the time it is 
dispensed and when it is returned.   The tube weights will be recorded on the CRF. 
Inventory records must be readily available for inspection by the trial monitor and/or auditor, and 
open to government inspection at any time. 
Study drug returned by subjects at Weeks 4 and 8 will be held on site until accountability has been 
completed. The site will be instructed on return or destruction of used and unused clinical supplies. 
8.7 
Prohibited Concomitant Therapy 
Any medication/therapy used by the subject following first application of study product will be 
considered a concomitant medication (e.g., aspirin, acetaminophen, birth control pills, vitamins, 
etc.). Every attempt should be made to keep concomitant medication/therapy dosing constant 
during the study. Any change to concomitant medications/therapies should be noted on the 
subject’s study record and in the study database. When applicable, an AE should be completed for 
any subject starting a concomitant medication/therapy after enrollment into the study. 
Immunosuppressive treatment is prohibited during the study. Use of topical calcineurin inhibitors 
or steroids on MC or within 2 cm of MC lesions is prohibited within 14 days of baseline and during 
the study. Use of the following concomitant medications to treat MC 14 days prior to baseline and 
during the study is prohibited: podophyllotoxin, imiquimod, cantharidin, sinecatechins, topical 
retinoids, oral or topical zinc, other homeopathic or OTC products including, but not limited to, 

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Zymaderm and tea tree oil, cimetidine and other histamine H2 receptor antagonists.   Surgical 
procedures (cryotherapy, curettage, other) are prohibited during the study. 
8.8 
Compliance 
Subjects will be provided a diary to record missed doses.  Review of subject compliance will be 
conducted at each visit and missed doses recorded on the subject diary will be recorded on the 
CRF.   
No reconciliation will be performed on the diary compliance against the tube weights.  Subject 
compliance will be based on calculation from the missed doses recorded from the subject diary 
only. 

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9 ADVERSE EVENTS 
The Investigator will assess subjects at each scheduled study visit for the occurrence of AEs.  In 
order to avoid bias in eliciting AEs, subjects/caregivers should be asked the following non-leading 
question: “How have you felt since your last visit?” Adverse events will be assessed and reported 
after the subject is dosed, beginning from Baseline through the end of the subject’s last visit. SAEs 
will be collected from the time of consent through the end of the subject’s last visit. 
9.1 
Documenting Adverse Events 
All AEs (serious and non-serious) reported by the subject must be recorded on the subject’s study 
record and entered into the study database.  The date of onset, date ended, seriousness, severity, 
outcome, relationship to study drug, therapy required, and action taken regarding study drug and 
study participation will be reported for each AE. 
9.2 
Assessment of Severity 
The Investigator is responsible for evaluating all AEs and determining the severity of the event.  
Severity will be categorized according to the following definitions: 
• Mild:  Event may be noticeable to subject; does not influence daily activities; usually 
does not require intervention 
• Moderate:  Event may be of sufficient severity to make subject uncomfortable; 
performance of daily activities may be influenced; intervention may be needed 
• Severe:  Event may cause severe discomfort; usually interferes with daily activities; 
subject may not be able to continue in the study; treatment or other intervention usually 
needed  
The Investigator will follow all subjects who experience AEs as described in Section 9.5. 
9.3 
Assessment of Causality 
Relationship of an AE to study drug will be assessed as follows: 
• Definite:  There is a clinically plausible time sequence between the onset of the AE and the 
application of study drug; when the event responds to withdrawal of Study drug and recurs 
with re-administration of study drug. 
• Probable:  There is a clinically plausible time sequence between the onset of the AE and 
the application of study drug; the AE is unlikely to be caused by the concurrent/underlying 
illness, other drugs or procedures. 
• Possible:  There may or may not be a clinically plausible time sequence between the onset 
of the AE and the application of study drug and a cause cannot be ruled out. 

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• Unlikely:  There is no reasonable temporal association between the test material and the 
suspected event and the event could have been produced by the subject's clinical state or 
other modes of therapy administered to the subject. 
• Unrelated:  This term should be reserved for those events that cannot be even remotely 
related to study participation. 
9.4 
Clinical Laboratory Changes 
Any clinically significant changes from Baseline in clinical laboratory values will be 
documented as an AE.   
9.5 
Adverse Event Follow-up 
9.5.1 
Follow-Up of Non-Serious Adverse Events 
Non-serious AEs that are not resolved at the time of the last scheduled study visit (Week 12/ET) 
must be recorded in the study database as ongoing/not recovered/not resolved. 
9.5.2 
Follow-Up of Post Study Serious Adverse Events 
Serious adverse events that are identified on the last scheduled contact (Week 12/ET) must be 
recorded in the study database and reported to the CRO according to the reporting procedures 
outlined in Section 10.2. This may include unresolved previously reported SAEs, or new SAEs. 
The Investigator should follow these SAEs until the events are resolved, or the subject is lost to 
follow-up. The Investigator should continue to report any significant follow-up information to the 
CRO and the IRB up to the point the event has been resolved. Resolution means the subject has 
returned to the baseline state of health, or the Investigator does not expect any further improvement 
or worsening of the subject’s condition. 
9.6 
Pregnancy 
Females 10 years of age and older must use an effective method of birth control during the course 
of the study and for 30 days following their final study visit. The following are considered 
acceptable methods of birth control for this study: abstinence with a documented acceptable 
method of birth control if the subject becomes sexually active oral contraceptives, contraceptive 
patches, contraceptive implant, vaginal contraceptive, double-barrier methods (e.g., condom and 
spermicide), contraceptive injection, IUD, hormonal IUD, permanent contraception, same sex 
partner or partner who has had a vasectomy. 
Before enrolling any subject in this clinical trial, the Investigator must review guidelines about 
study participation with the subject/caregiver, including the topics below: 
• Informed consent document 
• Pregnancy prevention information 

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• Risks to unborn child(ren) 
• Any drug interactions with hormonal contraceptives 
• Contraceptives in current use 
• Guidelines for the follow-up of a reported pregnancy 
Prior to study enrollment, all subjects must be advised of the importance of avoiding pregnancy 
during participation in this clinical study and the potential risk factors for an unintentional 
pregnancy. The subject must sign an informed consent document stating that the above-mentioned 
risk factors and the consequences were discussed. 
Cases of pregnancy that occur during maternal exposure to study drug should be reported. During 
the study, subjects should be instructed to contact the Investigator immediately if they suspect they 
might be pregnant (e.g., missed or late menstrual cycle). The Investigator must immediately notify 
the CRO of any female subject who becomes pregnant any time during study participation, record 
the information on the pregnancy notification form and email the form to the CRO. Subjects found 
to be pregnant prior to Week 12/ET will be discontinued from the study. The CRO will ask the 
site to follow-up with the subject periodically during the pregnancy for ongoing health and safety 
information through the end of the pregnancy as applicable. Protocol-required procedures for the 
Week 12/ET evaluation must be performed for the subject. 
9.7 
Overdose 
There is no specific antidote for SB206.  In the event of an overdose, best supportive care should 
be utilized.  Methylene blue may be used to treat subjects exhibiting methemoglobinemia. 

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10 SERIOUS ADVERSE EVENT 
10.1 Definition of Serious Adverse Event 
A SAE is any event that meets any of the following criteria: 
• Death 
 
• Life-threatening event (i.e., the subject was at immediate risk of death from the event as it 
occurred. It does not include a reaction that if it had occurred in a more serious form might 
have caused death. For example, drug induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life threatening even though drug induced hepatitis 
can be fatal.) 
• Inpatient hospitalization or prolongation of existing hospitalization (AEs requiring 
hospitalization should be considered SAEs. Hospitalization for elective surgery or routine 
clinical procedures that are not the result of AE (e.g., elective surgery for a pre-existing 
condition that has not worsened) need not be considered AEs or SAEs. If anything, 
untoward is reported during the procedure, that occurrence must be reported as an AE, 
either 'serious' or 'non-serious' according to the usual criteria. In general, hospitalization 
signifies that the subject has been detained (usually involving at least an overnight stay) at 
the hospital or emergency ward for observation and/or treatment that would not have been 
appropriate in the physician's office or outpatient setting. When in doubt as to whether 
'hospitalization' occurred or was necessary, the AE should be considered serious.) 
• Persistent or significant disability/incapacity (if the experience results in a substantial 
and/or permanent disruption of the subject's ability to carry out normal life functions) 
• Congenital anomaly/birth defect in the offspring of a subject who received SB206 or 
Vehicle Gel 
• Other: Important medical events that may not result in death, be life-threatening, or require 
hospitalization, may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. Examples of such events are: 
− Intensive treatment in an emergency room or at home for allergic bronchospasm 
− Blood dyscrasias or convulsions that do not result in inpatient hospitalization 
− Development of drug dependency or drug abuse 
 
 

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10.2 Reporting Serious Adverse Events 
Any SAE, whether deemed drug-related or not, must be reported to the CRO as soon as possible 
after the Investigator or coordinator has become aware of its occurrence. The 
Investigator/coordinator must notify the CRO within 24 hours of notification of the event. When 
appropriate, Novan will notify the appropriate regulatory body of drug related SAEs.  
If a subject experiences an SAE or pregnancy, the Investigator must: 
1. Report the SAE or pregnancy immediately (within 24 hours) after the Investigator becomes 
aware of the event. 
2. Complete an SAE or pregnancy notification form and send to the safety office within 24 
hours of knowledge of the event. 
3. Obtain and maintain all pertinent medical records, information and medical judgments of 
medical personnel who assisted in subject’s treatment and follow-up and document as 
appropriate. 
4. Provide a more detailed report to both the CRO and the IRB, if applicable, no later than 
seven days after the Investigator discovers the event as further information becomes 
available, and when necessary update the information with follow-up information 
including outcomes. This report should include a statement as to whether the event was or 
was not related to the use of study drug. 
5. The Investigator will notify the IRB of the SAE or pregnancy according to specific IRB 
requirements. 
6. The Investigator will collect information on SAEs until the subject’s health has returned to 
baseline status, until all parameters have returned to normal, or remaining health issues 
have otherwise been explained. 

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11 STATISTICS 
11.1 General Procedures 
Prior to the release of unblinded information through Cohort 3, a detailed, finalized Statistical 
Analysis Plan (SAP) will be completed and placed on file. The Statistical Analysis Plan will 
contain a more comprehensive explanation than that provided here of the methodology used in the 
statistical analyses, as well as the rules and data handling conventions used to perform the analyses 
and the procedure used to account for missing data. 
Safety and efficacy endpoints will be displayed using descriptive statistics and graphical displays. 
For categorical variables, frequencies, and percentages will be presented. The denominator for 
percentage will be based on the number of subjects appropriate for the purpose of analysis. 
Continuous variables will be summarized using descriptive statistics (number of subjects, mean, 
median, standard deviation [SD], minimum, and maximum). Where relevant, 95% confidence 
intervals will be calculated. Although analyses will be descriptive in nature, any statistical tests will 
be conducted at the 0.05 significance level using 2-tailed tests, and nominal p-values will be 
reported.  
11.2 Sample Size 
Approximately 192 subjects, 2 years of age and older, with a minimum of 3 and a maximum of 70 
lesions at baseline will be randomized across a minimum of 3 cohorts. If the third cohort is 
administered 12% BID,  up to an additional 64 subjects will be randomized in a fourth cohort.  
This Phase 2 study was not powered for formal statistical comparisons. The SB206 active dose 
groups will be compared to Vehicle gel. No adjustments will be made for multiplicity. No 
imputations will be utilized for safety or efficacy endpoints 
11.3 Analysis Populations 
The analysis populations include the following: 
The intent-to-treat (ITT) population will consist of all subjects who are randomized. 
The modified intent-to-treat (mITT) population will consist of all subjects who are randomized 
and complete the study treatment (subjects who complete 12 weeks of treatment and subjects who 
complete treatment due to clearance of all molluscum). 
The safety (SAF) population will consist of all patients who take at least one dose of study 
treatment. 
The exposure population will consist of all subjects who receive at least 1 application of active 
study medication and had a blood a blood sample collected and successfully analyzed for the 
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The per-protocol population (PP) will consist of all subjects in the mITT population and have no 
significant protocol deviations that impact the analyses of the efficacy endpoints.  
11.4 Statistical Methods 
11.4.1 
Demographic and Baseline Characteristics 
Subject demographic and Baseline characteristics will be summarized by treatment group for the 
SAF, mITT and ITT populations. Relevant medical history, current medical conditions, and any 
other relevant information will be listed by subject. 
11.4.2 
Efficacy Analysis 
The primary efficacy endpoint is the proportion of subjects achieving complete clearance of all 
molluscum contagiosum at Week 12 (subjects who achieved complete clearance before Week 12 
need to maintain complete clearance at Week 12) which will be analyzed by a logistic regression 
model with treatment, number of lesions at Baseline (3-18; 19-70) and atopic dermatitis history 
(with AD history vs w/o AD history) as factors. The primary analysis will compare each SB206 
dose level with the Vehicle using the mITT population. 
A sensitivity analysis of the primary endpoint will be repeated using the ITT and per-protocol 
population. Other sensitivity analyses may be performed and will be specified in the statistical 
analysis plan. 
Secondary endpoints will be analyzed on the mITT and ITT population as follows: 
• Proportion of subjects achieving complete clearance of all MC at each visit will be 
analyzed using the same logistic regression analysis specified in the primary analysis. 
• Time to complete clearance of all MC will be analyzed using Kaplan Meier methods.  
• Proportion of subjects achieving at least a 75% reduction from baseline in the number of 
MC at each visit will be analyzed using the same logistic regression analysis specified in 
the primary analysis. 
• Mean change and percent change from baseline in number of MC at each visit will be 
analyzed using a mixed-model repeated-measures (MMRM) analysis with treatment as the 
main effect, visit, number of lesions at Baseline (3-18; 19-70) and atopic dermatitis history 
(with AD history vs w/o AD history) as factors and treatment by visit as an interaction 
term. 
Details of all secondary and exploratory endpoints will be specified in the SAP. Additional 
exploratory analyses may be conducted, all analyses will be detailed in the SAP, which will be 
finalized before database lock. 

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11.4.3 
Analysis of Safety 
11.4.3.1 
Adverse Events 
All AEs that occur during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities (MedDRA) terminology. Treatment-emergent AEs (TEAEs) 
are defined as AEs with an onset on or after the date of the first study drug dose. Medical history 
noted prior to the first study drug administration that worsen after Baseline will also be reported 
as AEs and included in the summaries.  
Treatment-emergent AEs will be summarized by treatment group, the number of subjects 
reporting a TEAE, System Organ Class (SOC), preferred term, severity, relationship to study 
drug (causality), and seriousness.  When summarizing AEs by severity and relationship, each 
subject will be counted only once within a system organ class or a preferred term by using the 
event with the highest severity and greatest relationship within each classification. 
Serious AEs will be summarized by treatment group, severity, and relationship to study drug, 
and individual SAEs will be listed by subject. In addition, a list of subjects who prematurely 
discontinue from the study due to an AE will be provided. 
11.4.3.2 
Physical Examination 
Changes in physical examination from baseline to end of treatment will be summarized.  Any 
clinically significant changes from Baseline will be documented as an AE. 
11.4.3.3 
 Vital Signs  
Blood pressure and pulse will be summarized by treatment group from Baseline through Week 
12/ET.  Additionally, change from Baseline in vital signs will be summarized at Weeks 1, 2, 4, 8, 
and 12/ET.  Any clinically significant changes from Baseline will be documented as an AE. 
11.4.3.4 
Laboratory Assessments 
Blood chemistry and hematology values will be reported individually at Baseline and day of last 
dose, which may occur at any time during the study.  Therefore, the study day of the last dose will 
be used to assign the laboratory values to the closest study visit (Week 1, 2, 4, 8, or 12).  Laboratory 
test results will be summarized descriptively at Baseline and each visit.  Additionally, shifts from 
Baseline to each visit in laboratory test results based on normal ranges will be summarized with 
descriptive statistics.  The last laboratory evaluation prior to the first dose of study drug will be 
used as Baseline for all laboratory analyses.  Any clinically significant changes from Baseline will 
be documented as an AE. 
Methemoglobin will be reported as a percentage of hemoglobin.  Methemoglobin will be 
summarized descriptively by treatment group at Baseline and Weeks 1, 2, 4, 8 and 12/ET.  
Additionally, the change from baseline in methemoglobin will be summarized by treatment group 
at each post baseline visit. 

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11.4.3.5 
Urine Pregnancy Tests 
Urine pregnancy tests results for females 10 years of age and older will be presented in data 
listings by subject.   
11.5 Analysis of hMAP3 Plasma Concentrations 
Plasma concentrations of hMAP3, a silicon-containing hydrolyzed monomer of the polymeric 
NVN1000 drug substance will be determined.  Results will be presented in data listings by 
subject.  If quantifiable concentrations are observed, the results will be summarized 
descriptively.  
11.6 Interim Analysis 
After all subjects in Cohort 3 have completed their last study visits, the database for all subjects 
in Cohorts 1-3 will be frozen for purposes of an interim analysis of safety and efficacy data.  
While this interim analysis is being prepared, the study will complete through Cohort 4 and the 
final analysis will be based on all subjects in Cohorts 1-4: Cohort 4 (QD dosing of SB206 8% or 
12% vs. vehicle).   Personnel who are not otherwise involved in the study will prepare the 
unblinded data and summary tables for the interim analysis.  The interim analysis will not impact 
the final analysis since the study does not involve any formal hypothesis testing.   
 

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12 ETHICS AND RESPONSIBILITIES 
12.1 Good Clinical Practice 
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry E6 
Good Clinical Practice: Consolidated Guidance and the applicable regulatory requirements.  The 
Investigator must submit all essential regulatory documentation, as required by local and national 
regulations (including approval of the protocol and informed consent/assent form by an IRB) to 
the CRO before investigational product will be shipped to the study site.  The Investigator will 
review the final study results to confirm that to the best of his knowledge, it accurately describes 
the conduct and results of the study. 
12.2 Data Safety Monitoring Board 
After 30 subjects randomized in a cohort have completed 2 weeks of treatment, the Data Safety 
Monitoring Board (DSMB) will review the available unblinded safety and tolerability data.  Using 
predetermined criteria documented in the DSMB charter, the DSMB will determine if the data 
supports escalating to the next highest dose for the next cohort or if the data shows the dose is not 
tolerable, decreasing to the next lower dose or frequency for the next cohort. All responsibilities 
of the DSMB and details of data to be reviewed will be detailed in the DSMB charter. 
12.3 Institutional Review Board/Independent Ethics Committee 
The protocol, informed consent/ assent form(s), recruitment materials, and all participant materials 
will be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of 
both the protocol and the consent/assent form must be obtained before any subject is screened.  
Any amendment to the protocol will require review and approval by the IRB before the changes 
are implemented to the study.  In addition, all changes to the consent/assent form will be IRB-
approved; a determination will be made regarding whether a new consent needs to be obtained 
from subjects who provided consent, using a previously approved consent form. 
12.4 Informed Consent 
Informed consent is a process that is initiated prior to the subject agreeing to participate in the 
study and continues throughout the subject’s study participation. Consent/assent forms will be 
Institutional Review Board (IRB)-approved and the subject will be asked to read and review the 
document. The investigator will explain the research study to the subject and answer any questions 
that may arise. A verbal explanation will be provided in terms suited to the subject’s 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research subjects.  Subjects will have the opportunity to carefully review the written consent/assent 
form and ask questions prior to signing. The subjects should have the opportunity to discuss the 
study with their family or surrogates or think about it prior to agreeing to participate. The informed 
consent/assent document should be signed prior to any procedures being done specifically for the 
study. Subjects must be informed that participation is voluntary and that they may withdraw from 
the study at any time, without prejudice. A copy of the informed consent/assent document will be 
given to the subjects for their records. The informed consent process will be conducted and 

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documented in the source document (including the date), and the form signed, before the subject 
undergoes any study-specific procedures. The rights and welfare of the subjects will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study. 
12.5 Records Management 
It is the responsibility of the Investigator to ensure that the study center file is maintained in 
accordance with Section 8 – Essential Documents for the Conduct of a Clinical Trial of the ICH 
Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance and 21 CFR Part 312. 
12.6 Source Documentation 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  Data recorded on the  CRF derived from source documents should be 
consistent with the data recorded on the source documents. 
Clinical data will be entered into a 21 CFR Part 11-compliant data capture system provided by the 
CRO. The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will 
be entered directly from the source documents. 
12.7 Study Files and Record Retention 
It is a Novan requirement that all Investigators participating in clinical studies maintain detailed 
clinical data for one of the following periods, whichever is longest: 
• Country-specific requirements; or 
• A period of at least two years following the last approval of a marketing application 
approved by a Regulatory Authority in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region; or, 
• A period of two years after Novan notifies the Investigator that the data will not be 
submitted for review by any Regulatory Authority. 
The Investigator must not dispose of any records or essential documents relevant to this study 
without either (1) written permission from Novan, or (2) providing an opportunity for Novan to 
collect such records.  The Investigator shall take responsibility for maintaining adequate and 
accurate electronic or hard copy source documents of all observations and data generated during 
this study.  Such documentation is subject to inspection by Novan and relevant regulatory agencies.  
If the Investigator withdraws from the study (e.g., relocation, retirement), all study-related records 
should be transferred to a mutually agreed-upon designee.  Notice of such transfer will be provided 
to Novan in writing 

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13 AUDITING AND MONITORING 
13.1 Auditing 
In addition to the routine monitoring procedures, audits of clinical research activities in accordance 
with standard operating procedures (SOPs) may be performed to evaluate compliance with the 
principles of GCP.  A regulatory authority may also wish to conduct an inspection (during the 
study or even after its completion).  If a regulatory authority requests an inspection, the Investigator 
must inform the CRO immediately that this request has been made. 
Study conduct may be assessed during the course of the study by a Quality Assurance 
representative(s) to ensure that the study is conducted in compliance with the protocol and GCP.  
He/she will be permitted to inspect the study documents (study protocol, study records, 
investigational product, original, study-relevant medical records).  All subject data will be treated 
confidentially. 
13.2 Monitoring 
All aspects of the study will be monitored by the CRO or Novan according to Good Clinical 
Practices (GCP) and Standard Operating Procedures (SOPs) for compliance with applicable 
government regulations, (i.e., informed consent regulations, (21 C.F.R. § 50.20, 1999), and 
Institutional Review Board regulations, (21 C.F.R. § 56.103, 1981)).  Access to all records, both 
during the trial and after trial completion, should be made available to the CRO and Novan at any 
time for review and audit to ensure the integrity of the data.  The Investigator must notify the CRO 
immediately if the responsible IRB has been disqualified or if proceedings leading to 
disqualification have begun. 
The Investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines, applicable informed consent regulations (21 C.F.R. § 50.20, 1999), and in compliance 
with the principles in the Declaration of Helsinki.  Every attempt must be made to follow the 
protocol and to obtain and record all data requested for each subject at the specified times.  If data 
is not recorded per protocol, the reason(s) must be clearly documented on the study records. 
Before study initiation, at a site initiation visit or at a meeting with the Investigator(s), a CRO or 
Novan representative will review the protocol and study records with the Investigator(s) and their 
staff.  During the study, the study monitor will visit the site regularly to check the completeness of 
subject records, the accuracy of entries into the study database, the adherence to the protocol and 
to GCP, the progress of enrollment, to ensure that consent is being sought and obtained in 
compliance with applicable regulations, and that the investigational product is being stored, 
dispensed and accounted for according to specifications.  The Investigator and key trial personnel 
must be available to assist the monitor during these visits. 
The Investigator must give the monitor access to relevant hospital or clinical records to confirm 
their consistency with the study database entries.  No information in these records about the 
identity of the subjects will leave the study center.  Monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, documentation 

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of AEs/SAEs and the recording of primary efficacy and safety variables.  Additional checks of the 
consistency of the study records with the study database will be performed according to the study-
specific monitoring plan. 
The Investigator or designee must promptly enter the data into the study database after the subject’s 
visit.  The monitor is responsible for reviewing them and clarifying and resolving any data queries.  
A copy of the study records will be retained by the Investigator who must ensure that it is stored 
in a secure place with other study documents, such as the protocol, the Investigator’s Brochure and 
any protocol amendments. 
The Investigator must provide the CRO and the responsible IRB with a study summary shortly 
after study completion. 

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14 AMENDMENTS 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Novan. A protocol change intended to eliminate an apparent immediate hazard to 
subjects may be implemented immediately, provided the IRB/IEC is notified within 5 days. 
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB/IEC and the investigator must await approval before 
implementing the changes. Novan will submit protocol amendments to the appropriate regulatory 
authorities for approval. 
If in the judgment of the IRB/IEC, the investigator, and/or Novan, the amendment to the protocol 
substantially changes the study design and/or increases the potential risk to the subject and/or has 
an impact on the subject's involvement as a study participant, the currently approved written 
informed consent form will require similar modification. In such cases, informed consent will be 
renewed for subjects enrolled in the study before continued participation. 

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15 STUDY REPORT AND PUBLICATIONS 
Novan is responsible for preparing and providing the appropriate regulatory authorities with 
clinical study reports according to the applicable regulatory requirements. 
The publication policy of Novan is discussed in the investigator's Clinical Research Agreement. 

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16 STUDY DISCONTINUATION  
Both Novan and the Principal Investigator reserve the right to terminate the study at the 
investigator’s site at any time. Should this be necessary, Novan or a specified designee will inform 
the appropriate regulatory authorities of the termination of the study and the reasons for its 
termination, and the Principal Investigator will inform the IRB/IEC of the same. In terminating the 
study, Novan and the Principal Investigator will assure that adequate consideration is given to the 
protection of the subjects’ interests. 

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17 CONFIDENTIALITY 
All information generated in this study is considered highly confidential and must not be disclosed 
to any person or entity not directly involved with the study unless prior written consent is gained 
from Novan. However, authorized regulatory officials, IRB/IEC personnel, Novan and its 
authorized representatives are allowed full access to the records. 
Subject’s will only be identified at a minimum by unique subject numbers in the study database. 
If required, the subject's full name may be made known to an authorized regulatory agency or other 
authorized official. 

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18 REFERENCES 
 
1. 
Butala N, Siegfried E, Weissler A. Molluscum BOTE sign: a predictor of imminent 
resolution. Pediatrics. 2013 May;131(5):e1650-3. doi: 10.1542/peds.2012-2293. Epub 
2013 Apr. 1. 
2. 
Chen X, Anstey AV, Bugert JJ. Molluscum contagiosum virus infection. Lancet Infect 
Dis 2013; 13: 877–88. 
3. 
Dohil M, Lin P, Lee J, Lucky AW, Paller AS, Eichenfield LF. The epidemiology of 
molluscum contagiosum in children. J Am Acad Dermatol 2006; 54: 47-54. 
4. 
Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of 
atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad 
Dermatol. 2014; 71(1):116-132. 
5. 
Olsen, JR, Gallacher, J, Piguet, V, and Francis, NA. Epidemiology of molluscum 
contagiosum in children: a systematic review. Fam Pract. 2014; 31: 130–136. 
6. 
Olsen JR, Gallacher J, Finlay AY, Piguet V, Francis NA. Time to resolution and effect on 
quality of life of molluscum contagiosum in children in the UK: a prospective community 
cohort study. Lancet Infect Dis 2015; 15: 190–95.  
7. 
Ormerod AD, White MI, Shah SA, Benjamin N. Molluscum contagiosum effectively 
treated with a topical acidified nitrite, nitric oxide liberating cream. Br J Dermatol. 1999 
Dec;141(6):1051-3. 
8. 
Osio A, Deslandes E, Saada V, Morel P, Guibal F. Clinical characteristics of molluscum 
contagiosum in children in a private dermatology practice in the greater Paris area, 
France: a prospective study in 661 patients. Dermatology 2011; 222: 314–20.  
9. 
Schofield JK, Fleming D, Grindlay D, Williams H. Skin conditions are the commonest 
new reason people present to general practitioners in England and Wales. Br J Dermatol 
2011; 165: 1044–50. 
 

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19 APPENDICES 
19.1 APPENDIX I – Names of Study Personnel 
Sponsor: 
Novan, Inc. 
4105 Hopson Road 
Morrisville, NC 27560 
Clinical Research 
Organizations: 
Premier Research 
One Park Drive, Ste. 150 
Box 13608 
Research Triangle Park, NC 27709-0006 
Safety Number or 
Contact Email 
Tel: 215.282.5434 
Fax: 215.972.8765 
globalpv-US@premier-research.com