Clinical trial NCT04535531
Conditions: Molluscum Contagiosum
Sponsor: Novan, Inc.
Start date: 2020-09-01; Completion date: 2021-07-28
Enrollment: 891 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 3 multi-center, randomized, double-blind, vehicle-controlled, parallel group study to be conducted in up to approximately 850 subjects 6 months of age and older with molluscum contagiosum (MC). Subjects or their caregivers will apply SB206 10.3% or Vehicle Gel once daily for a minimum of 4 weeks and up to 12 weeks to all lesions identified at Baseline and new treatable lesions that arise during the course of the study.

Detailed description:
This is a phase 3 multi-center, randomized, double-blind, vehicle-controlled, parallel group study to be conducted in up to approximately 850 subjects 6 months of age and older with molluscum contagiosum (MC). After obtaining informed consent/assent, subjects who satisfy entry criteria will be randomized 1:1 (active:vehicle). Subjects receiving current treatment for MC at the time of the Screening Visit will enter a wash out period of up to 14 days prior to randomization.

Subjects or their caregivers will apply treatment once daily to all lesions identified at Baseline and new lesions that arise during treatment for a minimum of 4 weeks and up to 12 weeks. If the investigator determines all lesions are cleared at a visit, the treatment may stop. If treatment is stopped due to clearance, subjects will continue regularly scheduled visits through Week 24/ET2. Study drug will be dispensed through Week 12/ET1 in case of lesion recurrence between study visits. At each visit subsequent to stopping treatment due to clearance, the investigator will determine if new lesions have occurred since the last visit, and if so, the subject or caregiver will be instructed by the investigator to re-initiate treatment. If the subject or caregiver see new lesions or re-occurrence of lesions in between visits, they should treat these lesions until the next visit. No study drug will be provided after the Week 12 visit. The subject or caregiver will apply study drug to the individual lesions. Periocular lesions will be treated if the lesions are at least 2 cm from the edge of the eye. Subjects will visit the clinic in person at Screening/Baseline, Week 2, Week 4 (unless visit is performed remotely), Week 8, Week 12, and Week 24.

Arms: arm 1: SB206 10.3% berdazimer topically once daily arm 2: Vehicle gel topically once daily
Interventions: intervention 1: SB206 10.3% berdazimer intervention 2: vehicle gel
Intervention descriptions: intervention 1: Topically once daily intervention 2: Topically once daily

Protocol documents:
Prot_000.pdf: 
NI-MC304 Clinical Study Protocol 
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A Phase 3 Multi-Center, Randomized, Double-Blind, Vehicle-
Controlled, Parallel Group Study Comparing the Efficacy and 
Safety of SB206 and Vehicle Gel Once Daily in the Treatment of 
Molluscum Contagiosum 
 
A Phase 3 Molluscum Contagiosum Efficacy and Safety Study 
Investigational Product 
SB206 
Protocol Number 
NI-MC304 
Version Number 
3.0 
Version Date 
30 Sep 2020 
Amendment 
2 
IND Number  
137015 
Sponsor 
 
Novan, Inc. 
4105 Hopson Road, Suite 146 
Morrisville, NC 27560 
 
 


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CONFIDENTIALITY STATEMENT 
The information contained in this protocol and all other information relevant to SB206 are the 
confidential and proprietary information of 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. 
STATEMENT OF COMPLIANCE 
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCP) as outlined by ICH E6(R2), and all applicable local and national regulatory 
requirements. Enrollment at any clinical study site may not begin prior to that site receiving 
approval from the ethics committee of record for the protocol and all materials provided to 
potential participants. 
Any amendments to the protocol or changes to the consent document will be approved before 
implementation of that amendment. Reconsent of previously enrolled participants may be 
necessary depending on the nature of the amendment. 
The Principal Investigator will ensure that changes to the study plan as defined by this protocol 
will not be made without prior agreement from the sponsor and documented approval from the 
ethics committee of record, unless such a change is necessary to eliminate an immediate hazard 
to the study participants. 
All personnel involved in the conduct of this study have completed Human Subjects Protection 
and GCP Training as outlined by their governing institution. 
 
 
 


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SPONSOR’S APPROVAL 
Title 
A Phase 3 Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, Parallel 
Group Study Comparing the Efficacy and Safety of SB206 and Vehicle Gel Once Daily 
in the Treatment of Molluscum Contagiosum 
Protocol Number 
NI-MC304 
Version Number 
3.0 
Version Date 
30 Sep 2020 
Amendment 
2 
The design of this study as outlined by this protocol has been reviewed and approved by the 
sponsor’s responsible personnel as indicated in the signature table below. 
 
Medical Representative 
Name: 
Title: 
Signature: 
Date: 
Tomoko Maeda-Chubachi 
Vice President, Medical 
 
 
Regulatory Representative 
Name: 
Title: 
Signature: 
Date: 
Emily de León 
Senior Director of 
Regulatory Operations 
 
 
Biostatistics Representative 
Name: 
Title: 
Signature: 
Date: 
David Hebert 
Senior Director, Head of 
Biometrics 
 
 
 
 


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INVESTIGATOR’S AGREEMENT 
I have read the protocol, appendices, and accessory materials related to Study NI-MC304 and 
agree to the following: 
• To conduct this study as described by the protocol and any accessory materials 
• To protect the rights, safety, and welfare of the participants under my care 
• To provide oversight to all personnel to whom study activities have been delegated 
• To control all investigational products provided by the sponsor and maintain records of 
the disposition of those products 
• To conduct the study in accordance with all applicable local and national regulations, the 
requirements of the ethics committee of record for my clinical site, and Good Clinical 
Practices as outlined by ICH E6(R2). 
• To obtain approval for the protocol and all written materials provided to participants prior 
to initiating the study at my site 
• To obtain informed consent – and updated consent in the event of new information or 
amendments – from all participants enrolled at my study site prior to initiating any study-
specific procedures or administering investigational products to those participants 
• To maintain records of each subject’s participation and all data required by the protocol 
Name 
Title 
Institution 
 
 
 
Signature 
Date 
 
 
 
 
 


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SUMMARY OF CHANGES 
The major changes incorporated into this protocol (Version 3.0) relative to the prior approved 
version (Version 2.0) are summarized in the table below. 
Section 
Number 
Section Title 
Summary of Change 
Rationale for Change 
10.2.1 
Sample Size Rationale 
Increased to approximately 850 patients 
and updated supporting rationale 
Increased ability to detect 
treatment difference   
Multiple 
sections 
Changed throughout 
protocol for 
consistency 
Permit remote or in-clinic visit to be 
performed at Visit 4/Week 4, and in-clinic 
visit to be performed at V5/Week 8 
Ensuring data quality and 
operational ease for 
subjects/caregivers 
 
 
 
 


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TABLE OF CONTENTS 
CONFIDENTIALITY STATEMENT ........................................................................................... 2 
STATEMENT OF COMPLIANCE ............................................................................................... 2 
SPONSOR’S APPROVAL ............................................................................................................ 3 
INVESTIGATOR’S AGREEMENT ............................................................................................. 4 
SUMMARY OF CHANGES ......................................................................................................... 5 
TABLE OF CONTENTS ............................................................................................................... 6 
LIST OF TABLES ....................................................................................................................... 11 
LIST OF FIGURES ..................................................................................................................... 11 
LIST OF APPENDICES .............................................................................................................. 11 
LIST OF ABBREVIATIONS ...................................................................................................... 12 
1 
SYNOPSIS ....................................................................................................................... 14 
1.1 
Study Schematic............................................................................................................ 19 
1.2 
Schedule of Assessments .............................................................................................. 20 
2 
INTRODUCTION ........................................................................................................... 23 
2.1 
Background ................................................................................................................... 23 
2.1.1 
Target Indication and Population ............................................................................... 24 
2.1.2 
Description of SB206 ................................................................................................. 24 
2.1.2.1 
Administration Regimen ......................................................................................... 24 
2.1.2.2 
Justification for Dosing Strategy ............................................................................ 25 
2.1.3 
Supportive Nonclinical Data ...................................................................................... 25 
2.1.4 
Supportive Clinical Data ............................................................................................ 25 
2.1.4.1 
Clinical Pharmacology and Pharmacokinetics........................................................ 25 
2.1.4.2 
Clinical Safety ......................................................................................................... 27 
2.1.4.3 
Clinical Efficacy ..................................................................................................... 28 
2.1.5 
Benefit: Risk Assessment .......................................................................................... 30 
2.2 
Study Rationale ............................................................................................................. 30 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 31 
4 
STUDY PLAN ................................................................................................................. 32 
4.1 
Study Design ................................................................................................................. 32 
4.2 
Number of Participants and Study Sites ....................................................................... 35 
4.3 
Treatment Arms and Duration ...................................................................................... 35 


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5 
POPULATION ................................................................................................................ 35 
5.1 
Eligibility Criteria and Definitions ............................................................................... 35 
5.2 
Inclusion Criteria .......................................................................................................... 36 
5.3 
Exclusion Criteria ......................................................................................................... 36 
5.4 
Subject Screening.......................................................................................................... 37 
5.5 
Screen Failures .............................................................................................................. 38 
5.6 
Deviation from Inclusion/Exclusion Criteria ................................................................ 38 
6 
STUDY CONDUCT ........................................................................................................ 38 
6.1 
Study Procedures .......................................................................................................... 38 
6.2 
Subject Engagement and Retention .............................................................................. 39 
6.3 
Study Visit Scheduling ................................................................................................. 39 
6.4 
Remote Visits ................................................................................................................ 39 
6.5 
Unscheduled Visits ....................................................................................................... 40 
6.6 
Order of Assessments ................................................................................................... 40 
6.7 
Study Procedures by Time Point................................................................................... 40 
6.7.1 
Screening (Day –15 to Day 1) (In-Clinic Visit)......................................................... 40 
6.7.2 
Visit 1/Baseline (Day 1) (In-Clinic Visit) .................................................................. 41 
6.7.3 
Visit 2/Day 2 (Telephone Contact) ............................................................................ 42 
6.7.4 
Visit 3/Week 2 (Day 15 ± 3 days) (In-clinic Visit) ................................................... 42 
6.7.5 
Visit 4/Week 4 (Day 29 ± 5 days) (In-clinic or Remote Visit) .................................. 42 
6.7.6 
Visit 5/Week 8 (Day 57 ± 5 days) (In-clinic Visit) ................................................... 43 
6.7.7 
Visit 6/Week 12/ET (Day 85 ±5 days) (In-clinic Visit) ............................................ 43 
6.7.8 
Visit 7/Week 16 and Visit 8/Week 20 (Day 113 ±7 days; Day 141 ±7 days) 
(Telephone Contact)................................................................................................... 44 
6.7.9 
Visit 9/Week 24 (Day 169 ± 7 days) (In-clinic Visit) ............................................... 44 
6.8 
Discontinuation or Withdrawal ..................................................................................... 45 
6.8.1 
Individual Subjects..................................................................................................... 45 
6.8.2 
Treatment Modifications, Interruptions, and Discontinuation ................................... 45 
6.8.2.1 
Temporary Treatment Discontinuation ................................................................... 46 
6.8.2.2 
Permanent Discontinuation of Treatment ............................................................... 46 
6.8.3 
Withdrawal from Study.............................................................................................. 46 
6.8.4 
Replacement of Subjects ............................................................................................ 47 
6.8.5 
Subjects Lost to Follow-up ........................................................................................ 47 


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6.9 
Study Termination ........................................................................................................ 48 
7 
DESCRIPTION OF STUDY ASSESSMENTS .............................................................. 48 
7.1 
Efficacy Assessments.................................................................................................... 48 
7.1.1 
Molluscum Contagiosum Lesion Counts ................................................................... 48 
7.1.2 
Other Assessments ..................................................................................................... 49 
7.1.2.1 
BOTE Inflammation Score ..................................................................................... 49 
7.1.2.2 
Investigator Global Severity Assessment ............................................................... 50 
7.1.2.3 
Subject Global Severity Assessment ...................................................................... 50 
7.1.2.4 
Investigator Global Impression of Change ............................................................. 51 
7.1.2.5 
Subject Global Impression of Change .................................................................... 51 
7.1.2.6 
Study Exit Interview ............................................................................................... 51 
7.2 
Safety Assessments ....................................................................................................... 51 
7.2.1 
Physical Exam ............................................................................................................ 51 
7.2.2 
Pregnancy Testing ...................................................................................................... 52 
7.2.3 
Local Skin Reaction Assessment ............................................................................... 52 
7.2.4 
Scarring/Keloid Assessment ...................................................................................... 53 
7.2.5 
Diagnosis of Allergic Contact Dermatitis and Patch Testing .................................... 54 
7.2.6 
Adverse Events .......................................................................................................... 54 
8 
STUDY DRUG TREATMENT ....................................................................................... 54 
8.1 
Description of Products................................................................................................. 54 
8.1.1 
Formulation, Storage, Preparation, and Handling ..................................................... 55 
8.2 
Dosing and Administration ........................................................................................... 56 
8.3 
Treatment Allocation .................................................................................................... 57 
8.4 
Randomization Strategy and Procedure ........................................................................ 57 
8.5 
Extent and Maintenance of Blinding ............................................................................ 57 
8.5.1 
Unblinding Procedures............................................................................................... 57 
8.5.1.1 
Planned Unblinding ................................................................................................ 57 
8.5.1.2 
Unplanned or Unintentional Unblinding ................................................................ 58 
8.6 
Assessment and Verification of Compliance ................................................................ 58 
8.7 
Prior and Concomitant Therapies ................................................................................. 58 
8.7.1 
Prohibited Therapies .................................................................................................. 59 
9 
SAFETY MONITORING ................................................................................................ 59 


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9.1 
Definitions..................................................................................................................... 59 
9.2 
Documenting Adverse Events....................................................................................... 60 
9.2.1 
Assessment of Severity .............................................................................................. 61 
9.2.2 
Assessment of Causality ............................................................................................ 61 
9.2.3 
Reporting Serious Adverse Events ............................................................................ 61 
9.3 
Adverse Event Follow-up ............................................................................................. 62 
9.4 
Women of Childbearing Potential & Pregnancy .......................................................... 63 
9.5 
Overdose or Misuse ...................................................................................................... 64 
10 
ANALYSIS ...................................................................................................................... 64 
10.1 
Hypothesis..................................................................................................................... 64 
10.2 
Population ..................................................................................................................... 64 
10.2.1 
Sample Size Rationale ............................................................................................... 64 
10.2.2 
Analysis Subsets ........................................................................................................ 65 
10.2.3 
General Considerations .............................................................................................. 65 
10.3 
Testing Procedures ........................................................................................................ 66 
10.3.1 
Analysis of the Primary Efficacy Endpoint ............................................................... 66 
10.3.2 
Analysis of Secondary Efficacy Endpoints................................................................ 66 
10.3.3 
Population Analysis ................................................................................................... 67 
10.3.3.1 
Disposition .............................................................................................................. 67 
10.3.3.2 
Demographics and Baseline Characteristics ........................................................... 67 
10.3.4 
Safety Analysis .......................................................................................................... 67 
10.3.4.1 
Adverse Events ....................................................................................................... 67 
10.3.4.2 
Local Skin Reactions .............................................................................................. 68 
10.3.5 
Other Analyses ........................................................................................................... 68 
10.3.6 
Exploratory Analysis ................................................................................................. 68 
11 
ETHICAL CONSIDERATIONS ..................................................................................... 69 
11.1 
Good Clinical Practice .................................................................................................. 69 
11.2 
Data Safety Monitoring Board (DSMB) ....................................................................... 69 
11.3 
Ethics Review ............................................................................................................... 69 
11.4 
Informed Consent.......................................................................................................... 69 
11.5 
Data Privacy .................................................................................................................. 70 
11.6 
Disclosure ..................................................................................................................... 70 


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12 
OVERSIGHT ................................................................................................................... 70 
12.1 
Quality Control and Assurance ..................................................................................... 70 
12.1.1 
Monitoring ................................................................................................................. 70 
12.1.2 
Audits ......................................................................................................................... 72 
12.1.3 
Protocol Modification/Deviations .............................................................................. 72 
12.1.4 
Records ...................................................................................................................... 72 
12.1.4.1 
Data Capture and Management ............................................................................... 72 
12.1.4.2 
Source Documentation ............................................................................................ 73 
12.1.4.3 
Study Files and Records Retention ......................................................................... 73 
12.2 
Study Termination or Study Site Closure ..................................................................... 74 
13 
PUBLICATION POLICY ............................................................................................... 74 
14 
REFERENCES ................................................................................................................ 75 
 


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LIST OF TABLES 
Table 1 
Schedule of Assessments ..................................................................................... 21 
Table 2 
Overall Summary of TEAEs (Safety Population) through Week 24 ................... 27 
Table 3 
TEAEs in ≥ 2% of subjects in either SB206 treated group or Vehicle group (NI-
MC301) ................................................................................................................ 27 
Table 4 
TEAEs in ≥ 2% of subjects in either SB206 treated group or Vehicle group (NI-
MC302) ................................................................................................................ 28 
Table 5 
BOTE Inflammation Score .................................................................................. 50 
Table 6 
Local Skin Reaction Scale ................................................................................... 53 
Table 7 
Study Drug ........................................................................................................... 55 
Table 8 
Assessment of Causality ...................................................................................... 61 
Table 9 
Grading System for Patch Test Reactions (at each time point) ........................... 77 
Table 10 
Challenge Reaction Interpretation (based on the last reading (at least 48 hours 
after patch removal) ............................................................................................. 77 
 
LIST OF FIGURES 
Figure 1 
Study Timeline Diagram ...................................................................................... 20 
Figure 2 
NI-MC301: Percentage of Subjects with Complete Clearance............................ 28 
Figure 3 
NI-MC302: Percentage of Subjects with Complete Clearance............................ 29 
Figure 4 
Structure of Berdazimer Sodium (active ingredient in SB206) ........................... 56 
 
LIST OF APPENDICES 
Appendix 1 
Procedure for Suspected Sensitization ................................................................. 76 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AD 
Atopic Dermatitis 
AE 
Adverse Event 
BID 
Twice Daily 
BOTE 
Beginning-of-the-end 
BSA 
Body Surface Area 
CFR 
Code of Federal Regulations 
CM 
Concomitant Medication 
CRO 
Clinical Research Organization 
CSR 
Clinical Study Report 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
e-consent 
Electronic Consent 
eCRF 
Electronic Case Report Form 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimating Equation 
hMAP3 
Hydrolyzed N-Methylaminopropyl-trimethoxysilane 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD 
Intrauterine Device 
IUS 
Intrauterine Hormone Releasing System 
IWRS 
Interactive Web Response System 


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LLOQ 
Lower Limit of Quantitation 
LSR 
Local skin reaction (post exposure to study drug) 
MC 
Molluscum Contagiosum 
MedDRA 
Medical Dictionary of Regulatory Affairs 
NO 
Nitric Oxide 
NOVAN 
Novan, Inc. 
OTC 
Over the counter 
PK 
Pharmacokinetic 
PP 
Per-Protocol Population 
QD 
Once daily 
SAE 
Serious Adverse Event 
SAF 
Safety Population 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOA 
Schedule of Assessments 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Event 
UPT 
Urine Pregnancy Test 
 


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1 
SYNOPSIS 
Title 
A Phase 3 Multi-Center, Randomized, Double-Blind, Vehicle-
Controlled, Parallel Group Study Comparing the Efficacy and 
Safety of SB206 and Vehicle Gel Once Daily in the Treatment of 
Molluscum Contagiosum 
Short Title 
A Phase 3 Molluscum Contagiosum Efficacy and Safety Study 
Acronym 
B-SIMPLE4 
Phase 
3 
Study Design 
This is a phase 3 multi-center, randomized, double-blind, vehicle-
controlled, parallel group study to be conducted in up to 
approximately 850 subjects 6 months of age and older with 
molluscum contagiosum (MC). After obtaining informed 
consent/assent, subjects who satisfy entry criteria will be 
randomized 1:1 (active:vehicle). Subjects receiving current 
treatment for MC at the time of the Screening Visit will enter a 
wash out period of up to 14 days prior to randomization. In the 
event no wash out period is required, Screening and Baseline visit 
activities may be combined into a single visit. At randomization, 
subjects will be stratified by investigator type (dermatologist vs. 
other), the subject’s BOTE score at Baseline (no inflammation 
(BOTE = 0) vs. mild/moderate/severe inflammation (BOTE ≥ 1) 
and number of randomized subjects per household (1 subject per 
household vs. 2 subjects per household). Subjects will be stratified 
to 5 strata first by subjects per household. Subjects from 1 subject 
households will be stratified by investigator type and baseline 
BOTE score. Subjects from 2 subject households will not be 
further stratified with respect to investigator type and baseline 
BOTE score because the overall sample size that is expected for 
the stratum for households with two subjects is not large enough 
to support further stratification. 
The sponsor, investigator, site staff and study subjects will remain 
blinded to the study treatment during this study. All treatments are 
dosed topically, once daily (QD). Each dose will consist of 
berdazimer gel or vehicle gel that will be mixed with hydrogel on 
a supplied dosing guide, and then immediately applied by the 
subject to the affected designated area(s). 
 


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Subjects or their caregivers will apply treatment once daily to all 
lesions identified at Baseline and new lesions that arise during 
treatment for a minimum of 4 weeks and shall continue unless 
otherwise instructed by the investigator up to 12 weeks. If the 
investigator determines all lesions are cleared at a visit, the 
investigator may instruct the subject to stop treatment. If treatment 
is stopped due to clearance, subjects will continue regularly 
scheduled visits through Week 24/ET2. Study drug will be 
dispensed through Week 12/ET1 in case of lesion recurrence 
between study visits. At each visit subsequent to stopping 
treatment due to clearance, the investigator will determine if new 
lesions have occurred since the last visit, and if so, the subject or 
caregiver will be instructed by the investigator to re-initiate 
treatment. If the subject or caregiver see new lesions or re-
occurrence of lesions in between visits, they should treat these 
lesions until the next visit. No study drug is planned to be 
provided after the Week 12 visit.  
The subject or caregiver will apply study drug to the individual 
lesions. Periocular lesions will be treated if the lesions are at least 
2 cm from the edge of the eye.  
Subjects will visit the clinic in person at Screening/Baseline, 
Week 2, Week 4 (unless visit is performed remotely), Week 8, 
Week 12, and Week 24. At Baseline, the investigator will perform 
in person lesion counts. Then, the subjects/caregivers will be 
instructed on how to participate in remote visits and practice the 
technology. Once the initial in person lesion count has been 
completed by the assessor, an additional count by the same 
investigator will be made utilizing the remote technology platform 
to serve as a training for future remote visit.  
Subjects will be contacted via phone on Day 2 to collect subject 
information on early dose reactions. The Week 4 Visit may be 
performed remotely or as an in-clinic visit.  At Weeks 16 and 20, 
subjects will be contacted via phone to capture information 
regarding MC recurrence and adverse events (AEs); at Week 24, 
the subject will be seen at the site for a final study visit to assess 
scarring, keloids, and MC recurrence. Subjects who discontinue 
the study prior to the Week 12 visit due to AEs or other reasons 
will be asked to complete the Week 12 visit assessments; this will 


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be recorded as an Early Termination (ET1) visit. Subjects who 
discontinue from the study after Week 12 but prior to Week 24 
will be asked to come to the site to complete Week 24 
assessments; this visit will be recorded as an ET2 visit. 
Safety assessments include Beginning of the End (BOTE) 
Inflammation Scores, Local Skin Reactions (LSRs), adverse event 
collection, including presence of scars/keloids, and urine 
pregnancy tests (UPTs). Safety assessments except UPTs will be 
completed at all visits through Week 12; UPTs will be completed 
at Screening, Baseline, and Week 12. After Week 12, safety 
information for ongoing and new AEs will be collected, along 
with information regarding household MC occurrence. 
Additional procedures include subject/caregiver completion of a  
the Global Severity Assessment and the Global Impression of 
Change Assessment by the investigator and the subject/caregiver 
at Week 12 and 24. These procedures are designed to provide 
insight into the subject/caregiver’s experience with MC and 
current MC disease state. A select number of sites will also 
consent subjects/caregivers to participate in a study exit interview, 
to be arranged by a third party after completion of Week 12. The 
interview will include questions to further detail the 
subject/caregiver perspective of their MC and treatment 
experience. 
Target Population 
Males and females, 6 months of age and older, with a minimum of 
3 and a maximum of 70 MC lesions at Baseline 
Number of Subjects 
Approximately 850 
Subjects will be assigned 1:1 to active:vehicle.  
Length of Participation 
On treatment: Approximately 12 weeks 
Safety follow-up period: Approximately 12 weeks  
In study (including screening and safety follow-up): Up to 
approximately 26 weeks 


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Intervention 
SB206 10.3% or Vehicle Gel once daily  
Inflammatory reactions around the MC have been associated with 
imminent resolution of MC (sometimes referred to as “beginning-
of-the-end” [“BOTE”] sign). In most cases, clinical features can 
differentiate between BOTE and LSR. BOTE may be associated 
with itch, but not pain. BOTE is usually asymptomatic, self-
limited, localized to individual MC lesions, and does not require 
discontinuation of study treatment or additional treatment. LSR is 
generally more diffuse, associated with significant itch or 
tenderness, may necessitate discontinuation of study treatment, 
and may need treatment for symptomatic relief (e.g. a topical 
corticosteroid or topical anesthetic). For very severe LSR, 
systemic corticosteroids may be considered. Investigators will 
assess the treatment area at each scheduled visit and use their 
medical judgement to differentiate between BOTE and LSRs. The 
subject’s baseline skin inflammatory condition will be assessed as 
part of the physical examination to be completed prior to 
randomization. BOTE Inflammation Score and LSR scores will be 
recorded at each visit.  LSRs will be rated on individual features 
including erythema, flaking/scaling, crusting, swelling, 
vesiculation/pustulation, and erosion/ulceration. When LSRs are 
clinically significant, the investigator should report the condition 
as AE(s). 
Clinically significant LSRs that are reported as adverse events 
and/or subject reported intolerability (i.e. itching, pain) may result 
in an investigator directed temporary treatment hold (drug 
holiday), and topical corticosteroids may be used to treat LSRs for 
up to 2 weeks. Per the investigator’s instructions, the subject may 
re-initiate study drug treatment prior to the next scheduled visit. 
Upon re-initiation (challenge) of study drug treatment, if a subject 
develops worsening LSRs, allergic contact dermatitis may be 
suspected. In the event of suspected allergic contact dermatitis, 
photographs may be taken of the affected area(s) and transmitted 
to the contract research organization (CRO) medical monitor for 
review and confirmation of allergic contact dermatitis prior to 
initiating patch testing. Consent must be in place for patch testing 
to occur. The investigator should also discuss the necessity of 
patch testing with the subject/caregiver. The investigator will then 


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discontinue the subject from study drug treatment and treat the 
area(s) with corticosteroids for up to 2 weeks. If the subject 
provides consent/assent, the investigator will consult the CRO 
medical monitor prior to implementing the process for patch 
testing.  
Adverse events will be assessed and collected after the initiation 
of study drug treatment through the end of the subject’s last visit. 
Treatment related adverse events will be followed up until 
resolution or up to one year after last treatment, whichever is 
sooner.  
The investigator will map locations of the molluscum lesions at 
Baseline in clinic and through the remote visit platform. The 
investigator will count and record the number of active (raised, 
treatable) molluscum lesions per body area. Additional lesions 
identified through Week 12 will be mapped at each visit. Using 
the map as a guidance, the investigator will assess the treated 
areas for scar/keloid formation. Scar formation will be assessed 
starting at the Week 4 visit through Week 12 and again at Week 
24. Scars will be considered an adverse event for the purposes of 
this study. In addition, treatment related keloid/hypertrophic scars 
will also be recorded as adverse events.  
If a subject’s treatment is discontinued by the investigator or the 
subject because of an AE, that AE should be indicated as the 
reason for treatment discontinuation. All subjects will be 
encouraged to remain in the study throughout the 24-week study 
duration, even if treatment is discontinued prematurely. 
Primary Endpoint 
This study is being conducted to evaluate the efficacy and safety 
of SB206 10.3% QD for the treatment of MC. The primary 
endpoint will evaluate the proportion of subjects with complete 
clearance of all treatable MC at Week 12. 
Secondary Endpoints 
• Proportion of subjects achieving a lesion count of 0 or 1 of all 
treatable MC at Week 12 
• Proportion of subjects achieving at least a 90% reduction from 
Baseline in the number of all treatable MC at Week 12 
• Proportion of subjects with complete clearance of all treatable 
MC at Week 8 
• Percent change from Baseline in the number of all treatable MC 
at Week 4 


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Safety Endpoints 
• Incidence of treatment-emergent adverse events 
• Change from Baseline in LSR scores 
• Change from Baseline in abbreviated physical examinations 
• Concomitant medications reported 
• Proportion of subject(s) with reported scar(s) 
Other Endpoint 
• Change from Baseline in BOTE scores 
Exploratory Endpoints 
• Percent change from Baseline in number of treatable MC at 
Weeks 2, 8, and 12 
• Proportion of subjects achieving a lesion count of 0 or 1 of all 
treatable MC at Weeks 2, 4, and 8 
• Proportion of subjects achieving at least a 90% reduction from 
Baseline in the number of all treatable MC at Weeks 2, 4 and 8 
• Proportion of subjects achieving at least a 75% reduction from 
Baseline in the number of all treatable MC at Weeks 2, 4, 8 and 
12 
• Absolute change from Baseline in number of treatable MC at 
Weeks 2, 4, 8 and 12 
• Proportion of subjects with complete clearance of all treatable 
MC at Weeks 2 and 4 
• Time to complete clearance of all treatable MC 
• Proportion of subjects who have a recurrence of MC after the 
first visit at which complete clearance was observed  
• Subject-reported spread to household members as measured by 
any new occurrence of MC in household members of subjects at 
Weeks 2, 4, 8, 12 
• Investigator Global Severity Assessment at Baseline, Week 12 
and 24 
• Subject Global Severity Assessment at Baseline, Week 12 and 
24 
• Investigator Global Impression of Change at Week 12 and 24 
• Subject Global Impression of Change at Week 12 and 24 
Number of Sites 
Approximately 55 sites in the United States 
Study Duration 
Estimated start date: 01 Sep 2020 
Projected stop date: 31 Mar 2021  
Estimated duration: 3.5 months of enrollment 
1.1 
Study Schematic 
The study schematic is presented in Figure 1.


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Visit 5 
 
Day 57±5 
Visit 6/ET 1 
 
Day 85±5 
Visit 7 
 
Day 113±7 
Visit 8 
 
Day 141±7 
Visit 9/ET2 
 
Day 169±7 
Visit 4 
 
Day 29±5 
Figure 1 
Study Timeline Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
SB206 (berdazimer) gel 10.3% QD 
No treatment after Week 12 through 24 
 
 
 
Vehicle gel 
 
 
 
 
 
Screening 
Up to 2 
weeks 
Randomized Treatment Period (Double-Blind) 
12 weeks 
Safety Follow-Up Period (Double-Blind) 
12 weeks 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Subjects that do not require a washout may have Screening and Baseline procedures conducting on the same day. Screening/Baseline visits will be done in-
clinic if completed on the same day.  
*Week 12 procedures should be completed for subjects who early terminate (ET) from the study prior to Week 12; Week 24 procedures should be completed 
for subjects who ET after Week 12 but prior to Week 24.  
 
1.2 
Schedule of Assessments 
The schedule of assessments (SOA) is presented in Table 1. 
 
 


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Table 1 
Schedule of Assessments 
 
Screening 
Treatment 
 
Screening1 
(Day -15 to 
Day 1) 
Visit 11 
Baseline 
(Day 1) 
Visit 2 
TC 
(Day 2) 
Visit 32 
Week 2  
(Day 15 ±3) 
Visit 42 
Week 4 
(Day 29 ±5) 
Visit 52 
Week 8 
(Day 57 ±5) 
Visit 62 
Week 12/ ET1 
(Day 85 ±5) 
Informed Consent (Assent) 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
 
 
 
 
 
 
Molluscum Lesion Count  
X 
X3 
 
X 
X 
X 
X 
Physical Exam4 
 
X 
 
 
 
 
X 
Urine Pregnancy Test5 
X6 
X 
 
 
 
 
X 
BOTE Inflammation Score7 
 
X 
(pre-dose) 
 
X 
X 
X 
X 
Local Skin Reactions (LSR)8 
 
X 
(post-dose) 
 
X 
X 
X 
X 
Scarring/Keloid Assessment  
 
 
 
 
X 
X 
X 
Review of Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
Drug Dispensed 
 
X 
 
 
X 
X 
 
Collect Study Drug 
 
 
 
 
X 
X 
X 
Provide instructions on and test remote visit technology 
 
X 
 
 
 
 
 
Provide Subject Diary 
 
X 
 
 
 
 
 
Review Subject Application Instructions 
 
X 
 
X 
X 
X 
 
In Clinic Study Drug Application9 
 
X 
 
X 
X 
X 
X 
Review/reinforce Study Drug Compliance 
 
 
 
X 
X 
X 
X 
Record Adverse Event (AE) and Concomitant Medication 
(CM) Changes 
 
X 
X 
X 
X 
X 
X 
Household status of MC10 
X 
X 
 
X 
X 
X 
X 
Investigator Global Severity Assessment & Subject Global 
Severity Assessment  
 
X 
 
 
 
 
X 
Investigator Global Impression of Change & Subject Global 
Impression of Change 
 
 
 
 
 
 
X 
Consent for Study Exit Interview11 
 
X 
 
 
 
 
 


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Safety Follow-up  
 
Visit 7 
Week 16 TC 
(Day 113 ± 7 days) 
Visit 8 
Week 20 TC 
(Day 141 ± 7 days) 
Visit 9 
Week 24/ET2 
(Day 169 ± 7 days) 
Scarring/Keloid Assessment 
 
 
X 
Record Adverse Event (AE) and Concomitant Medications10 
X 
X 
X 
Household status of MC10 
X 
X 
X 
Investigator Global Severity Assessment & Subject Global Severity Assessment 
 
 
X 
Investigator Global Impression of Change & Subject Global Impression of Change 
 
 
X 
1 Screening and Baseline may occur on the same day. If this occurs, lesion count and review of inclusion/exclusion criteria will only occur once.  
2 All visit dates are in reference to Baseline (e.g. Week 2 occurs 14 days after Baseline Visit). The Week 4 visit may be performed remotely or in clinic. Baseline, Week 2, Week 
8, Week 12, and 24 visits will be performed in clinic. Day 2, Week 16, and Week 20 will be performed via phone. If a subject terminates early, an in-clinic visit is preferred, but 
a remote visit may be performed with sponsor approval. 
3 Lesion counts will be performed twice during the Baseline visit; the first assessment will be performed by the investigator in person, and the second assessment will be 
performed by the investigator through image evaluation. 
5 The physical exam will include a directed examination of the skin (presence or absence of individual features of erythema, flaking/scaling, crusting, swelling, 
vesiculation/pustulation, and erosion/ulceration. 
6 Females who have reached 9 years of age, unless they are post-menopausal (at least 12 months of continuous amenorrhea without an alternative medical cause), or surgically 
sterilized (documented hysterectomy, documented bilateral salpingectomy, or documented bilateral oophorectomy). Tubal ligation does not meet the definition of surgically 
sterile.  
7 UPT will be performed at Screening if the visit takes place in the clinic. 
8 BOTE Inflammation Score will be assessed pre-dose at Baseline. The Baseline LSR assessment should be done at least 30 minutes after study drug is applied on Day 1. After 
Baseline, BOTE Inflammation score and LSRs can be evaluated at any time pre- or post-dose during the visit, regardless of whether lesions are present and whether study drug 
is applied.   
9 Study drug application will occur in clinic at Baseline, Week 2, Week 4, Week 8, and Week 12. On days when a remote visit will occur, subjects/caregivers will not apply the 
study drug until the study visit so that the mixing/application of study drug can be observed by site staff during the remote visit. 
10 At Screening, subjects should be asked if any household members currently have MC. In addition to recording AE and CM changes, subjects should be asked if there are any 
new occurrences of MC in household members of subjects at each visit, except Day 2. 
11 Follow up interviews will be performed with selected consented subjects that complete Week 12. Consent can be obtained starting at Baseline, and the follow up interview will 
be performed with the subject/caregiver at a later date.   
NOTE: The Week 4 visit can be performed in clinic or remote. Baseline, Week 2, Week 8, Week 12, and Week 24 should be performed in clinic wherever possible. Day 2, Week 
16, Week 20 should be performed as telephone contacts. Unscheduled visits are permitted as needed for medical reasons. In-clinic unscheduled visits should be reserved for 
evaluation of adverse events, lesion clearance, and study drug dispensation as needed. Remote unscheduled visits may be utilized as well as/if applicable. 


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2 
INTRODUCTION 
2.1 
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% (FDA, 2020). 
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).  
Patients with atopic dermatitis (AD) 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 (Olsen et al., 2014). 
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 
occurred in 102 (41%) of 250 cases in the literature.  
Novan, Inc. (Novan) conducted Study NI-MC201, a phase 2, multi-center, double-blind, vehicle-
controlled ascending dose, 12-week study to assess the tolerability, safety, and efficacy of SB206 
in subjects with molluscum contagiosum. In this study, the safety and efficacy of SB206 was 
evaluated in 256 subjects, males and females, 2 years of age or older, with 3 to 70 MC lesions. 
Different concentrations and dosing frequency of SB206 were tested for up to 12 weeks and the 
number of the subjects of each dose group were: 47 (4% BID), 48 (8% BID), 47 (12% BID), 48 
(12% QD) and 66 (Vehicle). In the intent-to-treat (ITT) analysis, 37.5% of subjects achieved 
complete clearance when treated with SB206 12% QD, compared to 18.2% of subjects achieving 
complete clearance with vehicle BID/QD combined (p=0.024). 
Based on the clear treatment effect demonstrated in NI-M201,  Novan conducted two phase 3 
multi-center, randomized, double-blind, vehicle-controlled, parallel group studies of SB206 in 
subjects 6 months of age and older with molluscum contagiosum, NI-MC301 and NI-MC302. In 
NI-MC301, 352 subjects were randomized across 33 sites in the United States and had an 
average of 18.1 molluscum lesions at baseline and an average of age 7.1 years. The study 
discontinuation rate was 15.3%. In NI-MC302, 355 subjects were randomized across 33 sites in 


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the United States and had an average of 18.3 molluscum lesions at baseline and an average age 
of 6.5 years. The study discontinuation rate was 17.2%.  
The primary endpoint for these studies was the proportion of subjects in the ITT population with 
complete clearance of all treatable molluscum lesions at Week 12. Subjects with missing Week 
12 lesion count data were counted as non-responders. In NI-MC301, 25.8% achieved complete 
clearance at Week 12 with SB206 and 21.6% achieved complete clearance at Week 12 with 
Vehicle; 30.0% of subjects on SB206 and 20.3% of subjects on Vehicle in NI-MC302 achieved 
complete clearance at Week 12. Although the primary analysis alone did not achieve statistical 
significance at the 0.05 level in either study, there is a positive trend within and across both 
studies. An integrated analysis of the primary endpoint for the combined studies was performed. 
This post hoc analysis shows a continued trend of effectiveness by achieving statistical 
significance with a complete clearance of 27.9% for SB206 and 20.9% for vehicle (p= 0.0387). 
Based on these results, an additional phase 3 study, NI-MC304, is being conducted with SB206. 
Topical formulations of berdazimer sodium at concentrations ranging from 1-16% have been 
studied. Over 1900 healthy volunteers or subjects with MC, acne, genital warts, atopic 
dermatitis, psoriasis, or tinea pedis have been exposed to Vehicle and over 3,400 exposed to 
berdazimer sodium as of January 31, 2020. In clinical studies completed to date, topical 
application of berdazimer sodium has generally been well-tolerated with no safety concerns 
identified. Note that description of the concentration of SB products used nominal numbers 
based on percent berdazimer sodium historically. Novan has updated the naming convention to 
use percent berdazimer. Therefore, SB206 12% (nominal berdazimer sodium) is the same 
admixture formulation as SB206 10.3% (berdazimer). In this protocol, the nominal berdazimer 
sodium numbers remain in historical studies.  
2.1.1 
Target Indication and Population 
SB206 is being developed to treat molluscum contagiosum in children and adults. 
2.1.2 
Description of SB206  
SB206 is a topical gel, formed by mixing berdazimer gel and hydrogel. Berdazimer gel is a nitric 
oxide-releasing macromolecule containing covalently bound N-diazeniumdiolate nitric oxide 
donors; nitric oxide release from the macromolecule is initiated by mixing the berdazimer gel 
with hydrogel. A summary of nonclinical and clinical data is provided below; additional details 
are provided in the Investigator’s Brochure. 
2.1.2.1 
Administration Regimen 
Subjects will apply treatment once daily for up to 12 weeks to all active lesions identified at 
Baseline and new lesions that arise during treatment. If the investigator determines all lesions are 
cleared at a visit, the treatment may stop. If treatment is stopped due to clearance, subjects will 
continue regularly scheduled visits through Week 24 and study drug will be dispensed in case of 
lesion recurrence between study visits. Prior to Week 12, if lesions recur or new lesions appear 


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after the subject has cleared, treatment should be resumed. No further treatment will occur after 
Week 12. 
An increase in the number of MC lesions (with or without inflammatory reaction) during the 
early treatment period 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 berdazimer gel or vehicle gel with hydrogel thoroughly mixed together 
by the subject or caregiver on a supplied dosing guide and applied to the individual lesions. 
Periocular lesions will be treated if the lesions are at least 2 cm from the edge of the eye. If a 
subject has more than 20 MC, a second dose of berdazimer gel or vehicle gel with hydrogel can 
be prepared to ensure appropriate coverage of all lesions. 
2.1.2.2 
Justification for Dosing Strategy 
Based on totality of the data presented in Section 2.1, SB206 12% QD (now SB206 10.3% QD) 
was selected for this phase 3 study. 
2.1.3 
Supportive Nonclinical Data 
Novan has completed over 150 non-clinical studies during the development of multiple 
berdazimer sodium products (SB204, SB206, SB208, SB414) to assess pharmacology, PK, 
ADME, and toxicology. For additional nonclinical information refer to the Investigator’s 
Brochure (IB). 
2.1.4 
Supportive Clinical Data 
Over 5300 subjects have been treated, including over 3400 subjects who have been treated with 
topical berdazimer sodium (SB204, SB206, SB208, SB414) and over 1900 subjects have been 
treated with vehicle. The conditions investigated include acne, external genital warts and perianal 
warts, tinea pedis, psoriasis, atopic dermatitis and molluscum contagiosum. Topical 
administration of berdazimer sodium has had an overall favorable safety and tolerability profile. 
Application site pain has been the most common treatment related adverse event in completed 
studies. There has been no evidence of meaningful trends in safety parameters. There have been 
no clinically significant changes in physical examination in subjects treated with topical 
berdazimer sodium; however, there have been a few sporadic clinically significant changes 
identified in laboratory assessments and vital signs.  
2.1.4.1 
Clinical Pharmacology and Pharmacokinetics 
The systemic bioavailability of SB206 after dermal administration has been investigated in one 
maximal use study, NI-MC101 in patients, at least six months of age, with a minimum of 20 MC 
lesions at baseline. For 15 days, subjects received once daily field treatment, which totaled an 
area of 484 cm2, which approximates to 100 MC lesions. The PK profile was assessed after 
repeated topical application of SB206 under the maximal use condition. No detectable systemic 


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exposure on Day 1 to hydrolyzed N-methylaminopropyl-trimethoxysilane (hMAP3), a silicon 
containing component of the parent compound was noted. Further PK analysis of Day 15 
samples indicated two subjects demonstrated negligible systemic concentration of hMAP3: one 
showed one measurable time point with 5.12 ng/mL at 3 hours post dose among 3 time points 
(pre-dose, 1, and 3 hours post dose), and the other showed 4 measurable time points with the 
maximum concentration of 33.9 ng/mL at 3 hours post dose among 4 time points (pre-dose, 1, 3, 
and 6 hours post-dose). Plasma nitrate concentrations were within normal variability. The 
maximum recorded post-Baseline value for methemoglobin of the study was 2.8%, and 
methemoglobin values from the 2 subjects who showed systemic exposure did not exceed 2.2 %.  
In the NI-MC201 study, plasma hMAP3 concentrations in all PK blood samples at Week 12 or 
end or treatment were below the lower limit of quantitation (LLOQ). 
In addition, two other supportive studies with the berdazimer drug product SB204 have been 
conducted in adults and adolescent subjects with moderate to severe acne vulgaris, and no 
quantifiable systemic exposure was observed. In adult subjects with moderate to severe acne 
vulgaris (NI-AC101) administration of SB204 8% (berdazimer sodium gel 16% co-administered 
with hydrogel) or Vehicle Gel daily for 5 days to the face, chest, back, upper shoulders twice 
daily (BID) (17% body surface area [BSA]) showed no detectable systemic exposure on Day 1 
or Day 5 to hydrolyzed N-methylaminopropyl-trimethoxysilane (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 pharmacokinetic (PK) study (NI-AC103) in 
adolescents (ages 9-16 years) with moderate to severe acne vulgaris, SB204 4% was applied 
topically once daily (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 were noted.  
Additionally, in a 4-way, randomized, double-blind, cross-over study examining 
electrocardiogram (ECG) effects following SB204 application (NI-AC104), there was no 
quantifiable systemic exposure to hMAP3 and no difference in plasma nitrate levels in 48 
subjects with moderate to severe acne treated with SB204 (berdazimer sodium) 4%, SB204 
(berdazimer sodium) 12% or Vehicle Gel applied to 17% BSA. No changes in ECG were 
observed with therapeutic or supratherapeutic doses of SB204. 
In a 2-week atopic dermatitis (AD) study (NI-AD101), and a 4-week psoriasis study (NI-PS101), 
a limited number of subjects who received SB414 6% (berdazimer sodium ointment 12% co-
administered with buffered hydrogel) demonstrated quantifiable systemic exposure to the study 
treatment at limited time points. Although both SB206 and SB414 have the same active 
pharmaceutical ingredient, the formulations are different: SB206 is a gel and SB414 is a cream. 
The cream formulation of SB414 resulted in low and not quantifiable systemic exposure to 
hMAP3 observed in the NI-AD101 and NI-PS101 studies for all but 2 subjects at 12 hours post-


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dose. Note that SB414 formulation is cream while SB204 formulation is gel, similar to SB206. 
For more information, refer to the Investigator’s Brochure. 
2.1.4.2 
Clinical Safety 
It should be noted some subjects have experienced transient asymptomatic erythema at the 
application site within 5 minutes of dosing, which typically lasted ≤15 minutes. This is due to 
nitric oxide’s vasodilatory pharmacologic effect and is an expected event. 
Summaries of the safety analyses of the phase 3 studies (NI-MC301 and 302) are ongoing, and 
the CSRs are under preparation. The treatment emergent adverse event (TEAE) profile of SB206 
through the Week 24 was found to be favorable and was very similar between the two studies. 
Study drug discontinuations in the SB206 treatment arm were all due to application site reactions 
and no treatment-related serious adverse events were reported across both studies. 
Table 2 
Overall Summary of TEAEs (Safety Population) through Week 24 
 
NI-MC301 
NI-MC302 
 
Vehicle 
(n=116) 
SB206 
(n=235) 
Vehicle 
(n=117) 
SB206 
(n=237) 
Subjects who reported at least one TEAE 
36 (31.0%) 
115 (48.9%) 
30 (25.6%) 
120 (50.6%) 
Serious TEAE 
0 
0 
1 (0.9%) 
1 (0.4%) 
Treatment-related TEAE 
19 (16.4%) 
86 (36.6%) 
8 (6.8%) 
86 (36.3%) 
TEAE leading to study drug discontinuation 
1 (0.9%) 
7 (3.0%) 
1 (0.9%) 
17 (7.2%) 
The TEAEs reported in greater than 5% of subjects in the SB206 treated groups were application 
site pain and application site erythema, with the majority of these TEAEs being mild or moderate 
in severity.  
Table 3 
TEAEs in ≥ 2% of subjects in either SB206 treated group or Vehicle group 
(NI-MC301) 
 
Vehicle (n=116) 
SB206 (n=235) 
 
Mild 
Moderate 
Severe 
Mild 
Moderate 
Severe 
Application site pain 
8 (6.9%) 
0 
0 
34 (14.5%) 
16 (6.8%) 
1 (0.4%) 
Application site erythema 
2 (1.7%) 
1 (0.9%) 
0 
13 (5.5%) 
15 (6.4%) 
1 (0.4%) 
Application site pruritus 
0 
0 
0 
8 (3.4%) 
2 (0.9%) 
1 (0.4%) 
Pyrexia 
3 (2.6%) 
1 (0.9%) 
0 
7 (3.0%) 
4 (1.7%) 
0 
Application site exfoliation 
0 
0 
0 
4 (1.7%) 
5 (2.1%) 
1 (0.4%) 
Application site scar 
9 (7.8%) 
0 
0 
6 (2.6%) 
0 
0 
Application site swelling 
1 (0.9%) 
0 
0 
5 (2.1%) 
1 (0.4%) 
0 
Application site dermatitis 
1 (0.9%) 
0 
0 
1 (0.4%) 
3 (1.3%) 
1 (0.4%) 
Application site discolouration 
0 
0 
0 
5 (2.1%) 
0 
0 
Vomiting 
1 (0.9%) 
0 
0 
2 (0.9%) 
5 (2.1%) 
0 
Upper respiratory tract infection 
2 (1.7%) 
0 
0 
3 (1.3%) 
2 (0.9%) 
0 
 


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Table 4 
TEAEs in ≥ 2% of subjects in either SB206 treated group or Vehicle group 
(NI-MC302) 
 
Vehicle (n=117) 
SB206 (n=237) 
 
mild 
moderate 
severe 
mild 
moderate 
severe 
Application site pain 
1 (0.9%) 
1 (0.9%) 
0 
15 (6.3%) 
22 (9.3%) 
0 
Application site erythema 
0 
0 
0 
10 (4.2%) 
14 (5.9%) 
2 (0.8%) 
Application site dermatitis 
1 (0.9%) 
0 
0 
6 (2.5%) 
5 (2.1%) 
0 
Application site scar 
10 (8.5%) 
0 
0 
10 (4.2%) 
0 
0 
Application site exfoliation 
0 
0 
0 
3 (1.3%) 
5 (2.1%) 
1 (0.4%) 
Application site pruritus 
1 (0.9%) 
1 (0.9%) 
0 
3 (1.3%) 
5 (2.1%) 
0 
Application site swelling 
0 
0 
0 
1 (0.4%) 
5 (2.1%) 
1 (0.4%) 
Pyrexia 
2 (1.7%) 
0 
0 
5 (2.1%) 
2 (0.8%) 
0 
Application site vesicles 
0 
0 
0 
0 
5 (2.1%) 
0 
Dermatitis contact 
0 
0 
0 
3 (1.3%) 
3 (1.3%) 
0 
 
Additional details regarding safety are available in the Investigators Brochure (IB). 
2.1.4.3 
Clinical Efficacy 
Recently two phase 3 studies have been completed and the clinical study reports are under 
preparation. The primary efficacy endpoint for the studies was complete clearance of all treatable 
MC lesions at Week 12 in the ITT population. The proportion of subjects with complete clearance 
at each visit is shown in Figure 2 and Figure 3. 
Figure 2 
NI-MC301: Percentage of Subjects with Complete Clearance 
 
Note: Subjects with missing lesion count data at the Week of interest were counted as non-responders. 
0.0%
4.3%
10.3%
21.6%
0.4%
4.7%
15.3%
25.8%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
35.0%
Week 2
Week 4
Week 8
Week 12
Vehicle
SB206


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Figure 3 
NI-MC302: Percentage of Subjects with Complete Clearance  
 
Note: Subjects with missing lesion count data at the Week of interest were counted as non-responders. 
The proportion of subjects with complete clearance of all treatable molluscum lesions at Week 
12 in NI-MC301 was 25.8% for SB206 and 21.6% for vehicle (p=0.375) and 30.0% for SB206 
and 20.3% for vehicle (p=0.062) in NI-MC302. For the secondary endpoint, the proportion of 
subjects with complete clearance of all treatable molluscum lesions at Week 8 in NI-MC301 was 
15.3% for SB206 and 10.3% for vehicle (p=0.202) and 13.9% for SB206 and 5.9% for vehicle 
(p=0.028) in NI-MC302. The results of other endpoints are available in the IB. The Kaplan-
Meier analysis in both studies also support the effectiveness of SB206 by showing the reduction 
of time to complete clearance. 
Analysis of the integrated data from NI-MC301 and NI-MC302 resulted in statistically 
significance for complete clearance at Week 12 (p= 0.038). Analysis of data from NI-MC302 
study demonstrated substantial effectiveness for reducing lesions to 1 or 0 (p=0.011) and 
reducing lesions by at least 90% (p=0.002). SB206 demonstrated statistical effectiveness in 
complete clearance for up to 28%, reduced lesions to 1 or 0 for up to 39% and approximately 
37% of subjects achieved a 90% reduction in lesions in NI-MC302. In addition, subjects treated 
with SB206 showed a lower occurrence of scarring when compared to the vehicle arm. 
Molluscum, caused by a family of pox viruses, is known to occasionally heal with small pitting 
(scar formation).” 
0.0%
1.7%
5.9%
20.3%
1.3%
3.4%
13.9%
30.0%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
35.0%
Week 2
Week 4
Week 8
Week 12
Vehicle
SB206


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2.1.5 
Benefit: Risk Assessment 
Subjects may not expect to receive direct benefit from study drug treatment during study 
participation. This study is designed to provide information about the efficacy and safety of an 
investigational medication compared to placebo/vehicle.  
There is a theoretical risk of methemoglobinemia resulting from dermal application of NO, i.e., 
through NO binding with systemic hemoglobin and thus methemoglobin levels have been closely 
monitored in Novan clinical trials. There have been no reports of methemoglobinemia or 
observed methemoglobin levels greater than 4.7% in subjects treated with topical berdazimer 
sodium in completed studies. Fluctuations in methemoglobin during treatment have been similar 
in subjects treated with berdazimer sodium or vehicle. Methemoglobin increases following 
treatment are rare. In subjects treated with berdazimer sodium, there have been a few sporadic 
clinically significant changes identified in laboratory assessments and vital signs. There have 
been no clinically significant changes in physical examination. No related SAEs have been 
reported for berdazimer sodium. 
Based on the known mechanism of action of NO as a vasodilator, theoretical risks from systemic 
exposure after topical administration of berdazimer sodium include hypotension and headache. 
There have been no reports of hypotension and no clinically significant changes in vital signs 
(blood pressure, pulse) judged by the investigators to be related to the administration of 
berdazimer sodium in clinical studies performed to date. Reported rates of headache in the 
clinical development program to date are similar across berdazimer and vehicle-treated subjects.  
Note that transient asymptomatic erythema at the application site within 5 minutes of dosing, 
which typically lasts ≤15 minutes, is an expected sign. This is due to nitric oxide’s vasodilatory 
pharmacologic effect. 
2.2 
Study Rationale 
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 interferes in 
physician-patient relationships. Repeated ablative treatments are difficult. Procedural treatments 
as well as self-limiting resolution may result in scarring. Using anesthesia involves safety risk 
and costs. Not treating increases the potential of further dissemination of the disease. Prevention 
of further dissemination of the disease is also important from a public health perspective. Topical 
application of SB206 may accelerate resolution of MC without causing pain and/or scarring, 
decrease the frequency of ablative treatment, and provide an effective, convenient treatment 
option for patients with MC. 
 


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3 
OBJECTIVES AND ENDPOINTS 
Tier 
Objectives 
Endpoint(s) 
Primary 
Efficacy 
To evaluate the efficacy of 
SB206 10.3% as compared 
to Vehicle in subjects with 
molluscum contagiosum 
The proportion of subjects with complete clearance of all treatable 
MC at Week 12 
Secondary 
Efficacy 
Endpoints 
To evaluate the efficacy of 
SB206 10.3% as compared 
to Vehicle in subjects with 
molluscum contagiosum 
• Proportion of subjects achieving a lesion count of 0 or 1 of all 
treatable MC at Week 12 
• Proportion of subjects achieving at least a 90% reduction from 
Baseline in the number of all treatable MC at Week 12 
• Proportion of subjects with complete clearance of all treatable 
MC at Week 8 
• Percent change from Baseline in the number of all treatable MC 
at Week 4 
Safety 
endpoints 
To evaluate the safety of 
SB206 10.3% compared to 
Vehicle in subjects with 
molluscum contagiosum 
• Incidence of treatment-emergent adverse events 
• Change from Baseline in LSR scores 
• Change from Baseline in abbreviated physical examinations 
• Concomitant medications reportedProportion of subject(s) with 
reported scar(s) 
Other 
Endpoint 
To evaluate BOTE and 
SB206 10.3% compared to 
Vehicle in subjects with 
molluscum contagiosum 
• Change from Baseline in BOTE scores 
Exploratory 
endpoints 
To evaluate various 
efficacy and other 
parameters of SB206 
10.3% compared to 
Vehicle in subjects with 
molluscum contagiosum.  
• Percent change from Baseline in number of treatable MC at 
each visit (Weeks 2, 8, 12) 
• Proportion of subjects achieving a lesion count of 0 or 1 of all 
treatable MC at Weeks 2, 4 and 8 
• Proportion of subjects achieving at least a 90% reduction from 
Baseline in the number of all treatable MC at Weeks 2, 4 and 8 
• Proportion of subjects achieving at least a 75% reduction from 
Baseline in the number of all treatable MC at Weeks 2, 4, 8 and 
12 
• Absolute change from Baseline in number of treatable MC at 
Weeks 2, 4, 8 and 12 
• Proportion of subjects with complete clearance of all treatable 
MC at Week 2 and Week 4 
• Time to complete clearance of all treatable MC 
• Proportion of subjects who have a recurrence of MC after the 
first visit at which complete clearance was observed  
• Subject-reported spread to household members as measured by 
any new occurrence of MC in household members of subjects at 
each visit (Weeks 2, 4, 8, 12)  
• Investigator Global Severity Assessment at Baseline, Week 12 
and 24 
• Subject Global Severity Assessment at Baseline, Week 12 and 
24 
• Investigator Global Impression of Change at Week 12 and 24 
• Subject Global Impression of Change at Week 12 and 24 
 


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4 
STUDY PLAN 
4.1 
Study Design 
In response to the recent COVID-19 pandemic, it is imperative to include additional protections 
to enhance the assurance of subject safety while protecting the integrity of the clinical trial data. 
In alignment with the FDA’s recommendation to utilize electronic and remote methods, the NI-
MC304 study was designed to include remote technology for the study visits between Week 2 
and Week 12, our primary endpoint, in an effort to minimize the amount of time that subjects 
and caregivers are required to be present in clinic if necessary, while also minimizing the number 
of contacts for our site personnel (FDA, 2020). Subjects/caregivers and investigators will 
practice at least one (simulated) remote assessment at the Baseline visit to familiarize each party 
with the technology before the first remote use. The frequency of planned on-site monitoring 
visits will be reduced, and more frequent remote monitoring visits will be incorporated to 
support protection of all team members. Enhanced central monitoring, telephone contact with the 
sites to review study procedures, trial participant status, and study progress, or remote 
monitoring of individual enrolled trial participants, will be performed as outlined in the 
monitoring plan. Additional information will be captured on any protocol deviations that occur 
due to COVID-19. Finally, a clinical trial continuity plan has been established for situations to 
outline the current modifications in place and in case of further impact the existing study design 
and plans. The plan incorporates contingency measures for additional disruptions due to COVID-
19 and other unforeseen circumstances, provides a process for documenting any participants 
impacted by the circumstance and what was impacted. The statistical analysis plan (SAP) 
includes analyses that will be performed to address the impact of the implemented contingency 
measures, and any necessary ad hoc analyses not incorporated into the SAP will be discussed in 
the clinical study report.  
This is a phase 3 multi-center, randomized, double-blind, vehicle-controlled, parallel group study 
to be conducted in approximately 850 subjects with MC. After obtaining informed 
consent/assent, subjects who satisfy entry criteria will be randomized 1:1 (active:vehicle) using 
an interactive web response system (IWRS). Subjects receiving current treatment for MC at the 
time of the Screening Visit will enter a wash out period of up to 14 days prior to randomization. 
In the event no wash out period is required, Screening and Baseline visit activities may be 
combined into a single in-clinic visit. At randomization, subjects will be stratified by investigator 
type (dermatologist vs. other), the subject’s BOTE score at Baseline (no inflammation (BOTE = 
0) vs. mild/moderate/severe inflammation (BOTE ≥ 1) and number of randomized subjects per 
household (1 subject per household vs. 2 subjects per household). Subjects will be stratified to 5 
strata first by subjects per household. Subjects from 1 subject households will be stratified by 
investigator type and baseline BOTE score. Subjects from 2 subject households will not be 
further stratified with respect to investigator type and baseline BOTE score because the overall 
sample size that is expected for the stratum for households with two subjects is not large enough 
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A maximum of two subjects from the same household may be randomized to the study. They 
must be randomized on the same day and both must individually meet all inclusion/no exclusion 
criteria. For subjects in the same household, Screening can occur on different days; however, the 
Baseline visit must occur on the same day. Households randomizing two subjects will receive the 
same treatment assignment for both subjects.  
Subjects or their caregivers will apply SB206 10.3% or Vehicle Gel once daily for a minimum of 
4 weeks and shall continue unless otherwise instructed by the investigator up to 12 weeks to all 
lesions identified at Baseline and new treatable lesions that arise during the course of the study. 
Subjects or their caregivers will continue to treat the area until the next scheduled visit even if 
the lesion(s) clear. At each in-clinic and remote visit, the investigator will count and record the 
number of active (raised, treatable) molluscum lesions per body area. Complete clearance should 
be confirmed by an in-clinic lesion count before treatment is discontinued. If the investigator 
determines all lesions are cleared at a visit, the investigator may instruct the subject to stop 
treatment. If treatment is stopped due to clearance, subjects will continue regularly scheduled 
visits through Week 12/ET and all procedures outside of study drug activities should be 
continued. If lesions recur or new lesions occur between visits after being stopped due to 
clearance, the subject or caregiver should re-initiate treatment to the recurring and new lesions. A 
new kit should be dispensed at Weeks 4 and 8 regardless of lesion count so that treatment can be 
restarted if lesions are observed between visits. An unscheduled visit is not required for the 
subject/caregiver to resume treatment. No study treatment is planned to be dispensed after the 
Week 12 visit. 
Remote visits may be performed at Week 4 using remote technology. During the Baseline visit, 
the subject/caregiver will be instructed on the technology to be used for remote visits. After the 
initial molluscum lesion count is completed, it will be repeated by the same assessor and the 
subject/caregiver using the subject/caregiver’s electronic device that will be utilized to capture 
photographs for remote visits. This will provide the subject/caregiver an opportunity to practice 
with the technology and will allow for the assessor to understand lesion appearance in person 
compared to through the technology platform.  
Subjects will be contacted via phone on Day 2 to collect subject information on early dose 
reactions. At Weeks 16 and 20, subjects will be contacted via phone to capture information 
regarding MC recurrence and adverse events (AEs); at Week 24, the subject will be seen at the 
site for a final study visit to assess scarring, keloid, and MC recurrence.  
Subjects who discontinue the study prior to the Week 12 visit will be asked to complete the Week 
12 visit assessments in the clinic; this will be recorded as an Early Termination (ET1) visit. 
Subjects who discontinue from the study after Week 12 but prior to Week 24 will be asked to come 
to the site to complete Week 24 assessments; this visit will be recorded as an ET2 visit. 
Safety assessments include BOTE Inflammation Scores, Local Skin Reaction (LSR) scores, 
adverse event collection, including scarring/keloid and urine pregnancy tests (UPTs). Safety 


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assessments will be completed at specified visits through Week 12. Adverse events and 
concomitant medications will be reviewed and updated as needed at each visit through Week 24.  
Inflammatory reactions around MC lesions has been associated with imminent resolution of MC 
(sometimes referred to as “beginning-of-the-end” [“BOTE”] sign). The investigator (or 
designated evaluator) will assess the presence and overall degree of inflammatory reactions at 
MC lesions at Baseline (pre-dose) and Weeks 2-12 using the BOTE Inflammation Score 
(Section7.1.2.1). BOTE may be associated with itch, but not pain. BOTE is usually 
asymptomatic, self-limited, localized to individual MC lesions, and does not require 
discontinuation of study treatment or additional treatment. LSR is generally more diffuse, 
associated with significant itch or tenderness, may necessitate discontinuation of study treatment, 
and may need treatment for symptomatic relief (e.g. a topical corticosteroid or topical 
anesthetic). For very severe LSRs, systemic corticosteroids may be considered (Section 7.2.3 for 
additional details). Investigators will assess the treatment area at each scheduled visit and use 
their medical judgement to differentiate between BOTE and LSRs. BOTE Inflammation Score 
and LSR component scores will be recorded at each visit. When LSRs are clinically significant at 
the application site, the investigator should report the condition as AE(s). 
Prior to the first application of study drug at Baseline, the investigator will assess the subject’s 
skin as part of the physical examination, including the presence or absence of individual features 
of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. 
At Baseline (30 min. post-dose) and at Week 2 through Week 12 the evaluators will rate LSRs 
on individual features including erythema, flaking/scaling, crusting, swelling, 
vesiculation/pustulation, and erosion/ulceration using the LSR Assessment scale (Table 7).  
Adverse events will be assessed and collected after the initiation of study drug treatment through 
the end of the subject’s last visit. Treatment-related adverse events and all serious adverse events 
will be followed up until resolution or up to one year after last treatment, whichever occurs 
earlier.  
Scar formation (scars/keloids/hypertrophic scars) will be assessed starting at the Week 4 visit 
through Week 24. The investigator will map locations of the molluscum lesions at Baseline. 
Additional lesions identified through Week 12 will be added to the map. Using the map as a 
guidance, the investigator will assess the treated areas for scar/keloid formation. All scars, 
including keloid/hypertrophic scars, that develop after the Baseline assessment should be 
captured as AEs and assessed for relatedness to study treatment.  
If a subject’s treatment is discontinued by the investigator or the subject because of an AE, that 
AE should be indicated as the reason for treatment discontinuation. All subjects will be 
encouraged to remain in the study and to complete all required study visits throughout the 24-
week study duration. 


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A Data Safety Monitoring Board (DSMB) will review all available unblinded safety data 
(including completed patch testing results). Section 11.2 provides additional details regarding the 
DSMB.  
4.2 
Number of Participants and Study Sites 
Approximately 850 male and female subjects ages 6 months of age and older with a minimum of 
3 and a maximum of 70 molluscum lesions at Baseline will be enrolled at approximately 55 sites 
in the United States. 
4.3 
Treatment Arms and Duration 
A double-blind randomization will be generated that randomly allocates subjects to one of 2 
treatment arms (SB206 10.3% or Vehicle gel) in a 1:1 ratio, so that approximately 50% of 
subjects will be randomized to receive SB206 10.3% and 50% will be randomized to receive 
Vehicle gel. Subjects receiving current treatment for MC at the time of the Screening Visit will 
enter a wash out period of up to 14 days prior to randomization. In the event no wash out period 
is required, Screening and Baseline visit activities may be combined into a single visit.  
The sponsor, investigator, site staff and study subjects will remain blinded to the study treatment 
during this study. Each dose will consist of berdazimer gel or vehicle gel that will be mixed by 
finger with hydrogel on a supplied dosing guide, and then immediately applied topically by the 
subject to the affected designated area(s). Treatment will be applied once daily to all lesions 
identified at Baseline and new lesions that arise during treatment for a minimum of 4 weeks and 
shall continue unless otherwise instructed by the investigator up to 12 weeks. If the investigator 
determines all lesions are cleared at an in-clinic visit, the investigator may stop treatment. If 
treatment is stopped due to clearance, subjects will continue regularly scheduled visits through 
Week 24/ET, and study drug will be dispensed in case of lesion recurrence between study visits. 
If lesions recur or new lesions occur between visits after being stopped due to clearance, the 
subject or caregiver should reinitiate treatment to the recurring and new lesions. At each visit, 
sites should remind subjects/caregivers that if new lesions or recurring lesions are noticed 
between visits, treatment should be applied to those new or recurring lesions. The subject or 
caregiver will apply to the individual lesions. Periocular lesions will be treated if the lesions are 
at least 2 cm from the edge of the eye. 
5 
POPULATION 
5.1 
Eligibility Criteria and Definitions 
Subjects officially enter the Screening Period following provision of informed consent either 
directly, via a legal guardian, or a combination of both. Consent signatures may be obtained in 
person or via electronic consent. 


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A Screen Failure is a consented subject who has been deemed ineligible on the basis of 1 or more 
eligibility criteria or who has withdrawn consent prior to treatment assignment. Subjects may be 
rescreened once. 
A randomized subject is one who has been deemed eligible and has been assigned to a treatment 
group. To be eligible to participate in this study, a subject must meet the eligibility criteria - all 
of the Inclusion Criteria, and none of the Exclusion Criteria. 
5.2 
Inclusion Criteria 
To be considered eligible to participate in this study, the subject must satisfy all the following 
criteria: 
1. Be 6 months of age or older, and in good general health; 
2. Have a documented informed consent form signed by subject or a parent or legal 
guardian and an assent form as required;  
3. Have between 3 and 70 treatable MC lesions at Baseline; 
4. For women of childbearing potential (WOCBP): Must have a negative urine pregnancy 
test prior to randomization and must agree to use an effective method of birth control 
during the study; 
Note: WOCBP and effective methods of birth control are outlined in Section 9.4. 
5. Have a device (phone, tablet, personal computer, etc.) that will support remote visits, 
including a camera;  
6. Be willing and able to follow study instructions and likely to complete all study 
requirements, including remote study visits. 
5.3 
Exclusion Criteria 
Subjects will not be eligible for entry into this study if they meet any of the following criteria: 
1. Have strongly suggested sexually transmitted MC and do not agree to refrain from sexual 
activities throughout the study period; 
2. Are immunosuppressed, have immunodeficiency disorder, or are on immunosuppressive 
treatment; 
3. Have significant injury on and/or surrounding MC that may impact ability to treat and 
count lesions; 
4. Have received treatment with topical calcineurin inhibitors or steroids on MC or within 2 
cm of MC lesions within 14 days prior to Baseline; 
5. 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 over the counter (OTC) products including, but not limited 
to, ZymaDerm and tea tree oil, cimetidine and other histamine H2 receptor antagonists 
(including Zantac), or any agent that in the opinion of the investigator may be relevant – 
(e.g. wart therapies);  


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6. Have received surgical procedures related to MC (e.g. cryotherapy, curettage) within 14 
days prior to Baseline; 
7. Have MC only in periocular area; 
8. Female subjects who are pregnant, planning a pregnancy or breastfeeding; 
9. Have known hypersensitivity to any ingredients of SB206 or Vehicle Gel including 
excipients; 
10. Have participated in a previous study with a berdazimer containing product (i.e. SB204, 
SB206, SB208, SB414); 
11. Have more than one other family member participating in this study (NI-MC304); 
12. Have at least 1 family member currently participating in a study, other than this study, 
with a berdazimer containing product (i.e. SB204, SB206, SB208, SB414); 
13. Have participated in any other trial of an interventional investigational drug or device 
within 14 days or concurrent participation in another interventional research study; 
14. History or presence of clinically significant medical, psychiatric, or emotional condition 
that, in opinion of the investigator, would compromise the safety of the subject or the 
quality of the data. 
5.4 
Subject Screening 
Written informed consent (including 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/caregiver without first obtaining consent and/or 
assent. A hard-copy or electronic informed consent may be utilized. A subject wishing to 
participate must give documented 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 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 CRO for 
approval prior to submission to an Institutional Review Board (IRB) and/or Independent Ethics 
Committee (IEC) as appropriate, in cases in which a local IRB is being used. 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 


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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 the above activities must be 
completed before any study related procedures are conducted. 
5.5 
Screen Failures 
Study site personnel will use an interactive web response system (IWRS) system to assign a 
unique study number to each potential study participant, following informed consent. Subjects 
that ultimately do not meet eligibility criteria or who withdraw their consent prior to 
randomization will be considered a Screen Failure. The site will document the Screen Failure 
status in the IWRS and in their source documents/eCRF and will document their demographics 
and reason for screen failure. 
5.6 
Deviation from Inclusion/Exclusion Criteria 
Deviation from the inclusion/exclusion criteria is not allowed. Any deviation identified during 
the study will be documented and should be discussed with the CRO and/or sponsor. 
6 
STUDY CONDUCT 
6.1 
Study Procedures 
Subjects are expected to be in this study for up to 27 weeks. There is a 2-week 
screening/washout period if needed and the treatment period is expected to be a minimum of 4 
weeks and a maximum of 12 weeks. After the 12-week treatment period, subjects will enter a 12-
week safety follow-up period. The Schedule of Assessments (Table 1) summarizes the study 
procedures/assessments to be performed/collected at each study visit. Some Baseline/Day 1 
procedures (i.e. review of inclusion/exclusion criteria, brief physical examination including a 
directed assessment of skin condition prior to application of study drug, adverse event 
assessment, concomitant medication review, and UPT if applicable) 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 the same day. At Baseline, subjects at 
selected sites will have an opportunity to consent to a study exit interview. Once randomized, 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 as well as having in-clinic applications being 
performed at Week 2, Week 4 (if the visit is performed in the clinic), Week 8, and Week 12. 
Subjects/caregivers will be observed mixing and applying study drug during each study visit 
through the final scheduled dose of study drug during the Week 12 visit. Additionally, the 
Investigator and subject/caregiver will assess the impact of MC at Baseline, Week 12, and Week 
24. The Investigator and subject/caregiver will also complete the global impression of change at 


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Week 12 and Week 24. From Week 12 to Week 24, additional safety assessments will be 
performed, including scar assessment and household MC occurrence. 
6.2 
Subject Engagement and Retention 
It is important to support subjects and caregivers throughout their participation in this study and 
to provide a path for every subject to complete the study. To achieve this, Novan created an 
engagement and retention plan that includes the following, in addition to other supportive 
processes: 
• Remote visits, to decrease subject/caregiver burden and exposure 
• Daily dosing reminders and appointment reminders  
• Brief (1-3 minute) educational videos, including training on normal lesion healing 
• Study-related retention items, provided at each visit  
• Certificate of participation 
• Travel and childcare reimbursement as needed 
• Site outreach to subject/caregiver after a missed visit  
• Standardized follow up letter process if subject/caregiver are unresponsive to contacts 
(Section 6.8.5) 
Additional details can be found in the Study Procedures Manual. This plan will continue to be 
revised as study circumstances evolve. 
6.3 
Study Visit Scheduling 
At the end of each study visit the next visit should be scheduled/confirmed. Screening, Baseline, 
Week 2, Week 8, Week 12 and Week 24 visits are to be performed in the clinic, with the option 
to perform Week 4 in clinic or remotely. A reminder of the next scheduled visit date will be 
shared with the subject. Every effort should be made to adhere to the allowable study visit 
window period as described in the Schedule of Assessments (Table 1). All visit dates are in 
reference to Baseline Day 1. In the event that a subject visit is performed out of window or if a 
visit is skipped, every effort should be made to get the subject to return for the next visit or 
complete the early termination visit if the subject is discontinuing from the study. A text 
messaging service or application may be utilized during the trial to send reminders and other 
educational messages to subjects/caregivers throughout the course of the study. 
6.4 
Remote Visits 
Week 4 can be performed as a remote visit or in clinic visit. All subjects/caregivers will be 
instructed on the technology to be utilized during the Baseline visit. Approximately 24-48 hours 
in advance of the remote visit, the subject or caregiver should utilize the historic lesion map to 


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take images of all lesion areas noted at the previous visit and any new lesion areas that developed 
since the previous visit. Photographs of the lesions should be taken prior to IP application for the 
day or at least 1 hour after application. The remote visit should be rescheduled within visit 
window if acceptable images have not been received by the site. Additional instructions on how 
to take and upload photographs is provided in the Study Reference Manual.  
6.5 
Unscheduled Visits 
The investigator may deem it clinically necessary to conduct visits outside of the ones specified 
in the Schedule of Assessments, in order to investigate a possible adverse event, follow up on 
adverse events, etc. The date and reason for the Unscheduled visit should be recorded in the 
source documents, with the specific procedures performed determined by the investigator, and in 
consultation with the medical monitor as needed, depending on the reason for the visit. In-clinic 
unscheduled visits should be reserved for assessment or follow-up of AEs and dispensation of 
drug. Remote visits can be used when possible. 
6.6 
Order of Assessments 
At the Baseline visit on Day 1, the physical examination and BOTE Inflammation Score should 
be done prior to randomization to study treatment. For WOCBP (see definition in Section 9.4), 
the UPT must be done prior to randomization. The initial Local Skin Reaction (LSR) assessment 
should be done at least 30 minutes after study drug is applied on Day 1. The BOTE and LSR 
assessments should be completed at each scheduled visit even if the subject is not going to be 
dosed or if the MC lesions have cleared. It may be most convenient to perform lesion counting, 
mapping, and scarring assessments immediately following the BOTE and LSR assessments. In 
order to ensure consistent counting of MC lesions, the same assessor should complete the lesion 
counts at all visits, but at a minimum, at Baseline and Week 12.  
6.7 
Study Procedures by Time Point 
6.7.1 
Screening (Day –15 to Day 1) (In-Clinic Visit) 
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 documented consent/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]), household 
MC status, medication history, and concomitant medication information. 
4. Perform lesion mapping and lesion count.   


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5. If applicable and visit is conducted in clinic, obtain UPT and evaluate results. If pregnancy 
test is positive, the subject may not participate in the study. 
6. Review inclusion/exclusion to confirm whether subject qualifies to participate in the study. 
6.7.2 
Visit 1/Baseline (Day 1) (In-Clinic Visit) 
The following procedures must be performed and recorded at the Baseline visit. If Screening and 
Baseline visits occur the same day, procedures with an asterisk (*) should only be performed once 
and will be recorded as Baseline values.  
1. Perform a brief physical examination, including the directed examination of the skin 
(presence or absence of individual features of erythema, flaking/scaling, crusting, 
swelling, vesiculation/pustulation, and erosion/ulceration). 
2. Perform lesion mapping and lesion count.* 
3. Perform BOTE Inflammation Score (pre-dose). 
4. Complete Investigator Global Severity Assessment. 
5. Complete Subject Global Severity Assessment. 
6. Obtain UPT, as applicable. If pregnancy test is positive, the subject may not participate in 
the study.*  
7. Update concomitant medication information. 
8. Confirm eligibility and randomize subject. 
9. Provide subject diary and dispense study drug.  
10. Weigh and record study product tubes.  
11. Instruct and practice remote visit technology with subject/caregiver, preferably on the 
device that will be used for the duration of the study. The investigator should review and 
perform a lesion count with the captured images.  
12. Instruct subject on dispensing, mixing, and application of study product and diary 
completion. 
13. Have subject/caregiver apply first dose in clinic from kit assigned at randomization. 
14. Complete Local Skin Reaction assessment approximately 30 minutes post dose. 
15. Collect and record AE information for any AEs reported. 
16. Confirm household MC status (any new cases in household members since screening 
visit).* 


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Note: Follow up interviews will be performed with a subset of subjects that complete Week 
12. Consent will be obtained between screening and the Week 12 visit. The follow up 
interview will be performed with the subject/caregiver at a later date after Week 12 is 
completed. 
6.7.3 
Visit 2/Day 2 (Telephone Contact) 
The following procedure must be performed and recorded at the Day 2 telephone contact. 
1. Contact subject to confirm how the subject is feeling and assess if any changes to AEs or 
concomitant medications. 
6.7.4 
Visit 3/Week 2 (Day 15 ± 3 days) (In-clinic Visit) 
The following procedures must be performed and recorded at the Week 2 visit. 
1. Perform BOTE Inflammation Score. 
2. Complete Local Skin Reaction Assessment. 
3. Perform lesion counting and mapping and update lesion map with location for any new 
lesions. 
4. Review study drug compliance/diary completion.  
5. Review dosing instructions and observe the subject/caregiver apply daily dose using the 
kit assigned at randomization. 
6. Collect and record AE information for AEs reported. 
7. Update concomitant medication information and confirm if any new occurrences of MC 
were reported in the subject’s household. 
6.7.5 
Visit 4/Week 4 (Day 29 ± 5 days) (In-clinic or Remote Visit) 
This visit can occur in clinic or be performed as a remote visit. If this visit is performed remotely, 
subjects/caregivers will upload images of all treatable lesions for the site to review in advance of 
the visit. If additional images are required, the site will notify the subject and provide any necessary 
feedback. The remote visit should be rescheduled within visit window if acceptable images have 
not been received by the site. Additional details on this process are found in the Study Reference 
Manual. If this visit is performed in clinic, no images are required, and the visit procedures are 
expected to be completed while the patient is in clinic. The following procedures must be 
performed and recorded at the Week 4 visit. 
1. Perform BOTE Inflammation Score. 
2. Perform Local Skin Reaction Assessment. 
3. Perform lesion counts and update lesion map with location for any new lesions. 
4. If previously cleared, assess for subject recurrence of MC. 
5. Perform scarring/keloid assessment; if present, document location on lesion map and 
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6. Weigh returned study drug and review study compliance.* 
7. Weigh, record, and dispense new supply of study product.* 
8. Review dosing instructions and observe subject/caregiver apply daily dose. 
9. Collect and record AE information for AEs reported. 
10. Update concomitant medication information and confirm if any new occurrences of MC 
were reported in the subject’s household. 
* Note: If Visit 4 is performed as a remote visit, the subject/caregiver can return the study 
drug kit and receive a new kit after completion of the remote visit and within the 
established visit window. If Visit 4 is performed in clinic, the subject/caregiver will 
return the study drug kit and will receive a new kit while in clinic. 
6.7.6 
Visit 5/Week 8 (Day 57 ± 5 days) (In-clinic Visit) 
The following procedures must be performed and recorded at the Week 8 visit. 
1. Perform BOTE Inflammation Score. 
2. Perform Local Skin Reaction Assessment. 
3. Perform lesion counts and update lesion map with location for any new lesions.  
4. If previously cleared, assess for subject recurrence of MC. 
5. Perform scarring/keloid assessment; if present, document location on lesion map and 
record as an AE. 
6. Weigh returned study drug and review study compliance. 
7. Weigh, record, and dispense new supply of study product. 
8. Review dosing instructions and observe subject/caregiver apply daily dose. 
9. Collect and record AE information for AEs reported. 
10. Update concomitant medication information and confirm if any new occurrences of MC 
were reported in the subject’s household. 
6.7.7 
Visit 6/Week 12/ET (Day 85 ±5 days) (In-clinic Visit) 
The following procedures must be performed and recorded at the Week 12/ET visit. 
1. Obtain pregnancy test and evaluate results, as applicable.  
2. Perform BOTE Inflammation Score. 
3. Perform Local Skin Reaction Assessment. 
4. Perform lesion counts and update lesion map with location for any new lesions. 
5. If previously cleared, assess for subject recurrence of MC. 
6. Perform scarring/keloid assessment; if present, document location on lesion map and 
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7. Perform a brief physical examination. 
8. Complete Investigator Global Severity Assessment and Investigator Global Impression of 
Change Assessment. 
9. Complete Subject Global Severity Assessment and Subject Global Impression of Change 
Assessment. 
10. Subject/caregiver administer final dose of study drug from previously dispensed kit only if 
lesions are present.  
11. Weigh returned study drug and review study compliance. 
12. Collect and record AE information for AEs reported. 
13. Update concomitant medication information and confirm if any new occurrences of MC 
were reported in the subject’s household. 
14. Review interview procedures with the subject/caregiver and obtain documented 
ICF/assent. 
Note: Follow up interviews will be performed with a subset of subjects that complete Week 
12.  Consent will be obtained during the Week 12 visit, and the follow up interview will be 
performed with the subject/caregiver at a later date. 
6.7.8 
Visit 7/Week 16 and Visit 8/Week 20 (Day 113 ±7 days; Day 141 ±7 days) 
(Telephone Contact) 
The following procedures must be performed and recorded at the Week 16 and Week 20 visits. It 
is expected that these visits should be done by telephone. 
1. Collect and record information for new and ongoing AEs, including recurrence of MC. 
2. Confirm household MC status (any new cases in household members since last visit). 
3. Update concomitant medication information. 
6.7.9 
Visit 9/Week 24 (Day 169 ± 7 days) (In-clinic Visit) 
The following procedures must be performed and recorded at the Week 24 visit. 
1. Perform scarring/keloid assessment; if present, document location on lesion map and 
record as an AE. 
2. Complete Investigator Global Severity Assessment and Investigator Global Impression of 
Change. 
3. Complete Subject/Caregiver Global Severity Assessment and Subject Global Impression 
of Change. 
4. Collect and record information for new and ongoing AEs, including subject recurrence of 
MC. 
5. Confirm household MC status (any new cases in household members since last visit visit). 
6. Update concomitant medication information. 


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6.8 
Discontinuation or Withdrawal 
6.8.1 
Individual Subjects 
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 permanently 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 the subject is encouraged to follow the visit 
schedule and complete all assessments, particularly those at Week 12 and 24.  
6.8.2 
Treatment Modifications, Interruptions, and Discontinuation 
If a subject experiences an LSR (AE) for the first time, the investigator must confirm if treatment 
is needed, if a treatment modification (hold treatment for certain areas) is needed, and/or if a 
treatment interruption (discontinue treatment in all areas) is needed. If the investigator confirms 
treatment is needed, the subject can continue study treatment on all areas, hold treatment in 
certain areas, or interrupt treatment completely, and add non-medicated treatment such as 
petroleum gel as a concomitant medication. This option can be exercised at any point during the 
study as needed.  
If no concomitant treatment is added, the investigator may choose to withhold study treatment on 
either specific areas (modification) or all areas (interruption) until the investigator confirms it is 
appropriate to continue. It is recommended to modify or interrupt treatment for 2-3 days before 
re-starting the study treatment; the investigator should use their discretion for when to reinitiate 
treatment by discussing the status of the AE with the subject/caregiver to determine if the event 
is resolved or if continued modification/interruption of study treatment is necessary. The 
investigator will confirm when reintroduction of study treatment can occur. This option can be 
exercised at any point during the study as needed. 
For more severe AEs, concomitant treatment such as corticosteroids can be added while 
withholding study treatment on specific areas (modification) or all areas (interruption) until the 
investigator confirms it is appropriate to continue with the study drug. Similar to the 
modifications and interruptions above, it is recommended to modify or interrupt treatment for 2-
3 days before re-starting the study treatment; the investigator should discuss the status of the AE 
with the subject/caregiver to determine if the event is resolved or if continued 
modification/interruption of study treatment is necessary. The investigator will confirm when 
reintroduction of study treatment can occur. This option can also be exercised at any point during 
the study as needed. 
After the resolution of the first LSR and reinitiation of treatment, if a more severe second LSR 
occurs, it is appropriate to suspect the cause is allergic contact dermatitis. Study treatment on all 
areas should be discontinued, and after resolution of the second LSR, patch testing is 


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recommended if the subject/caregiver consents. This step should be exercised only if the LSR is 
more severe than previous LSR(s). See Appendix 1 for additional information. 
6.8.2.1 
Temporary Treatment Discontinuation 
The investigator may instruct the subject to temporarily hold treatment to a specified region or 
completely (i.e., due to an adverse event). This treatment modification and the reason for the 
temporary drug interruption should be documented in the subject’s source documents. The 
lesions in the impacted area should continue to be counted in the lesion count during the period 
of treatment modification. See Section 6.8.2 for additional details.  
6.8.2.2 
Permanent Discontinuation of Treatment 
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. See Section 6.8.2 for additional details.  
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: 
• Complete clearance confirmed by investigator prior to Week 12 
• Adverse Event (including LSRs deemed to be significant by investigator) 
• Withdrawal of Consent by Subject/Caregiver 
• Lost to Follow-Up 
• Other 
6.8.3 
Withdrawal from Study 
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 prior to the 


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Week 12 visit, every effort should be made to have the subject return to the study site to 
complete the Week 12 evaluations (ET1 visit). If the subject/caregiver is unable or unwilling to 
return to clinic for the Week 12 visit, the investigator should discuss with the medical monitor 
the option to perform a remote Week 12 visit. All premature discontinuations and their causes 
must be carefully documented in the subject’s study record and in the study database. 
All Week 12 evaluations should be performed at the time of premature discontinuation as 
applicable if the subject discontinues prior to Week 12. If the subject discontinues after the Week 
12 visit, the Week 24 evaluations should be performed. All data gathered on the subject prior to 
termination will be made available to the CRO. The investigative site should make all reasonable 
efforts to ensure the subject returns to complete the termination visit, even if the subject is not 
able to attend other study visits.  
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: 
• Withdrawal of Consent by Subject/Caregiver 
• Lost to Follow-Up 
• Adverse Event 
• Other  
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. 
6.8.4 
Replacement of Subjects 
Subjects who withdraw from the study will not be replaced.  
6.8.5 
Subjects Lost to Follow-up 
All subjects who fail to return to the study site 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 three 
documented attempts (one attempt on three different days using at least 2 different forms of 
communication), a certified letter will be sent requesting that the subject contact the investigator 
to confirm the final status of their molluscum lesions and to return any outstanding study drug. 
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. The certified letter should include the following questions:  
• Please choose one of the following:  
o I/my child want to continue participating in this study.  


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o I/my child am no longer interested in participating in this study and withdraw my 
consent. 
• At the time you chose to stop participating in study visits, was your/your child’s 
molluscum contagiosum:  
o Resolved (no lesions left) 
o Resolving (number of lesions is decreasing) 
o Unchanged (number of lesions is similar to previous visit) 
o Worsening (number of lesions increased) 
An investigator may withdraw a subject from the study when a subject is lost to follow-up. 
6.9 
Study Termination 
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. 
7 
DESCRIPTION OF STUDY ASSESSMENTS 
The following study assessments will be done. Additional details can be found in in the Study 
Reference Manual and in the supportive online trainings. 
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 raised 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. If the investigator cannot clearly differentiate the lesions as is the case 
for agminated (clustered) lesions this should be counted as one lesion. If the investigator can 
differentiate and count the umbilical tops separately, each lesion should be counted separately. 
The investigator should be consistent with the method of recording agminated lesions throughout 
the study. 
For the purpose of this clinical trial, only treatable MC lesions are counted. Treatable lesions are 
any active (raised, palpable) MC lesions that are dome-shaped, pearly, and shiny white top 
centered papules that are at least 2 cm away from the ocular region. In clinic, investigators may 
choose to palpate the lesion to confirm if it is raised. Treatable region is any skin area containing 
a molluscum lesion, with the exception of the periocular region.  


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All study personnel who will perform lesion counts must pass the study training including lesion 
count training. Training on how to accurately count the number of MC lesions will be provided.  
Mapping of lesions: At every visit from Baseline through Week 12, all lesions should be 
recorded on the body map and will clearly note the location of each lesion or agminated lesion. 
The lesion map is intended to assist study personnel in performing lesion counting and 
scar/keloid assessment. The body map will also be shared with the subjects/caregivers at Week 2 
to assist with counting of lesions. 
Definition of Clearance: For the purpose of this study, “clear” means resolution of the active 
(raised, palpable) treatable molluscum lesion(s). After a lesion has cleared, the residual surface 
changes such as a pitted scar (indentation), hyperpigmentation, or hypopigmentation may 
remain. Additional details will be provided in the lesion count training. Complete clearance can 
only be confirmed by an in-clinic lesion count. 
The same evaluator should perform lesion counts at Screening, Baseline, and Weeks 2, 4, 8 and 
12/ET. In the event that this is not possible due to unforeseen circumstances, a different 
evaluator may evaluate the subject. All evaluators must pass the study training including lesion 
count training. It is particularly important to ensure the same evaluator performs the Baseline and 
Week 12/ET for lesion counts for a subject, 
7.1.2 
Other Assessments 
7.1.2.1 
BOTE Inflammation Score 
Inflammatory reactions around MC lesions has been associated with imminent resolution of MC 
(sometimes referred to as “beginning-of-the-end” [“BOTE”] signs). Investigators should educate 
subjects and caregivers on the characteristic stages of BOTE as it is recognized as the natural 
course of self-limiting clearance of MC. BOTE may be associated with itching, but not pain. 
BOTE is usually asymptomatic, self-limited, localized to individual MC lesions, and does not 
require discontinuation of study treatment or additional treatment.  
Investigators will assess the treatment area at each scheduled visit and use their medical 
judgement to differentiate between BOTE and LSRs. The BOTE Inflammation Score will be 
recorded at each visit (Table 5).  
 
 


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Table 5 
BOTE Inflammation Score 
Score 
Global Assessment 
Description 
0 
No inflammation 
No evidence of local inflammation 
1 
Mild 
Minimal erythema and/or edema 
2 
Moderate 
Definite erythema and/or edema with or without 
hemorrhagic crusting 
3 
Severe 
Erythema and edema with definite hemorrhagic crusting 
4 
Very Severe 
Strong reaction spreading beyond the treated area, 
bullous reaction, erosions 
7.1.2.2 
Investigator Global Severity Assessment  
The Investigator Global Severity Assessment will be completed by the investigator to assess 
overall impression of severity of MC and completed at Baseline, Week 12, and Week 24. The 
investigator will be asked to answer the following question:  
Please choose the response below that best describes the overall molluscum severity of the 
subject. 
0. None 
1. Mild 
2. Moderate 
3. Severe 
4. Very severe 
7.1.2.3 
Subject Global Severity Assessment  
The Subject Global Severity Assessment will be completed by the subject/caregiver to assess 
overall impression of severity of MC and completed at Baseline, Week 12, and Week 24. The 
subject or caregiver will be asked to answer the following question:  
Please choose the response below that best describes the severity of your/your child’s molluscum 
contagiosum today. 
0. None 
1. Mild 
2. Moderate 
3. Severe 
4. Very severe 


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7.1.2.4 
Investigator Global Impression of Change 
The Investigator Global Impression of Change will be completed by the investigator to assess 
their overall impression of change from baseline in overall MC condition at Weeks 12 and 24. 
The investigator will be asked to answer the following question:  
Please choose the response below that best describes the overall change in the subject’s 
molluscum contagiosum since he or she started taking the study medication. 
1. Very much improved 
2. Much improved 
3. Minimally improved 
4. No change 
5. Minimally worse 
6. Much worse 
7. Very much worse 
7.1.2.5 
Subject Global Impression of Change 
The Subject Global Impression of Change will be completed by the subject/caregiver to assess 
their overall impression of change from baseline in overall MC condition at Weeks 12 and 24. 
The subject or caregiver will be asked to answer the following question:  
Please choose the response below that best describes the overall change in your/your child’s 
molluscum contagiosum since you/your child started applying the study medication. 
1. Very much improved 
2. Much improved 
3. Minimally improved 
4. No change 
5. Minimally worse 
6. Much worse 
7. Very much worse 
7.1.2.6 
Study Exit Interview 
Study exit interviews may be conducted with a selected subset of subjects that complete Week 
12. Consent will be obtained starting at Baseline, and the professional interview will be 
performed with the subject/caregiver after completion of Week 12. The objective of the 
interview is to better understand the subject/caregiver perspective of their MC and treatment 
experience. 
7.2 
Safety Assessments 
7.2.1 
Physical Exam 
A brief physical examination will be performed to evaluate objective anatomic findings. This 
physical examination will be performed at Baseline and at Week 12/ET. At Baseline, the 
physical examination will include a directed examination of the skin condition prior to any 


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application of study drug. This skin assessment will include the presence or absence of 
individual features of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and 
erosion/ulceration. Any clinically significant changes in the physical exam from baseline will be 
recorded as AEs. 
7.2.2 
Pregnancy Testing 
Urine pregnancy testing will be required for females 9 years of age and older unless they are 
post-menopausal or surgically sterile (see Section 9.4). UPTs will be collected at Screening (if in 
-clinic visit), Baseline, and Week 12/ET. In addition to having a negative UPT at Baseline, 
before the first application of study drug, females who are 9 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: hormonal contraceptives (combined estrogen 
and progestogen or progestogen only, including oral, injectable, transdermal or injectable 
formulations); intrauterine device (IUD); intrauterine hormone releasing system (IUS); bilateral 
tubal occlusion or ligation if performed ≥ 3 months prior to Baseline; same sex partner or partner 
who has had a vasectomy ≥ 3 months prior to Baseline; sexual abstinence with a documented 
acceptable method of birth control if the subject becomes sexually active; female or male 
condoms with or without spermicide; or a cervical cap, diaphragm, or sponge with spermicide. 
Women with tubal occlusion or ligations or whose partner had a vasectomy will be required to 
complete UPTs at the required timepoints if their procedure was done < 3 months prior to 
Baseline. Tubal ligations or occlusion procedures should be recorded as part of the subject’s 
medical history if applicable. 
7.2.3 
Local Skin Reaction Assessment 
The investigator (or designated evaluator) will assess localized skin reactions (LSRs) at Baseline 
(at least 30 minutes post-dose), and at any time during the visit at Weeks 2, 4, 8 and 12. The 
individual components of LSRs are scored separately on a scale of 0-4, with higher numbers 
indicating more severe reactions. The individual components include erythema, flaking/scaling, 
crusting, swelling, vesiculation/pustulation, and erosion/ulceration.  
Compared to BOTE, LSRs are generally more diffuse, associated with significant itch or 
tenderness, may necessitate discontinuation of study treatment, and may need treatment for 
symptomatic relief (e.g. a topical corticosteroid or topical anesthetic). For very severe LSR, 
systemic corticosteroids may be considered. 
Investigators will assess the treatment area at each scheduled visit and use their medical 
judgement to differentiate between BOTE and LSRs. When LSRs are clinically significant in the 
opinion of the investigator (i.e. they interfere with the subject’s normal daily activities), s/he 
should report the condition as an AE(s) (e.g. application site erythema, application site edema). 
Clinically significant LSRs that are reported as adverse events and/or subject reported 
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(drug holiday), and topical corticosteroids may be used to treat LSRs for up to 2 weeks. The 
subject may re-initiate study drug treatment prior to the next scheduled visit. Upon re-initiation 
(challenge) of study drug treatment, if a subject develops worsening LSRs (more severe than the 
first LSRs), allergic contact dermatitis may be suspected. In the event of suspected allergic 
contact dermatitis, photographs may be taken of the affected area(s) and transmitted to the CRO 
medical monitor for review and confirmation of allergic contact dermatitis prior to initiating 
patch testing. Consent must be in place for patch testing to occur. The investigator should also 
discuss the necessity of patch testing with the subject/caregiver. The investigator will then 
discontinue the subject from study drug treatment and treat the area(s) with corticosteroids for up 
to 2 weeks. If the subject provides consent/assent, the investigator will consult the CRO medical 
monitor to implement the process for patch testing. See Section 7.2.5 for information on patch 
testing. 
Table 6 
Local Skin Reaction Scale 
 
Erythema 
Flaking/ 
Scaling 
Crusting 
Swelling 
Vesiculation/ 
Pustulation 
Erosion/ 
Ulceration 
0 
Not present 
Not present 
Not present 
Not present 
Not present 
Not present 
1 
Slightly pink 
Mild, 
limited 
Isolated 
crusting 
Minimal, 
limited 
Fine vesicles 
Superficial 
erosion 
2 
Pink or light 
red 
Moderate 
Crusting      
< 50% 
Mild, 
palpable 
Scant 
transudate or 
exudate 
Moderate 
erosion 
3 
Red, 
restricted to 
treatment area 
Coarse 
Crusting      
> 50% 
Moderate 
Moderate 
transudate or 
exudate 
Marked, 
extensive 
4 
Red 
extending 
outside 
treatment area 
Scaling 
extending 
outside 
treatment 
area 
Crusting 
extending 
outside 
treatment 
area 
Marked 
swelling 
extending 
outside 
treatment 
area 
Marked 
transudate or 
exudate 
Black eschar 
or ulceration 
7.2.4 
Scarring/Keloid Assessment 
Scar formation (scars/keloids/hypertrophic scars) will be assessed starting at the Week 4 visit 
through Week 12 and again at Week 24. Using the lesion map as a guide, the investigator will 
assess the treated areas for scar/keloid formation. All scars, including keloid/hypertrophic scars, 
that develop after the Baseline assessment should be captured as AEs and assessed for 
relatedness to study treatment.  


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7.2.5 
Diagnosis of Allergic Contact Dermatitis and Patch Testing  
After treatment is reintroduced post-LSR, if a subject experiences a stronger LSR (second LSR 
event) than the first LSR event, allergic contact dermatitis may be suspected. In order to confirm 
whether the reaction is allergic contact dermatitis, patch testing should be conducted. If the 
investigator determines that patch testing is appropriate, he/she should contact the CRO medical 
monitor to discuss next steps. Patch testing supplies will be provided once requested from the 
CRO medical monitor. Additional drug product for patch testing may be supplied through IWRS 
if the currently assigned subject’s investigational product was assigned more than 60 days prior 
to the patch testing date(s) or if the subject had previously returned all their drug product. 
Additionally, patch testing should be discussed with the subject/caregiver. If the 
subject/caregiver consents to patch testing and once the LSR has been completely resolved for a 
period of 2 weeks and up to 2 months, patch testing will commence. If allergic contact dermatitis 
is suspected, study drug should be permanently discontinued and an AE of allergic contact 
dermatitis should be recorded as the reason for discontinuation. Week 12/ET assessments should 
be completed at the time of discontinuation.  
In the event of suspected allergic contact dermatitis developed, photographs may be taken of the 
affected area(s) and transmitted to the CRO medical monitor for review prior to initiating patch 
testing. See Appendix 1 for further information. 
7.2.6 
Adverse Events  
Adverse events will be assessed and collected after the initiation of study drug treatment through 
the end of the subject’s last visit. Treatment-related adverse events and serious adverse events 
will be followed up until resolution or up to one year after last treatment, whichever occurs 
earlier. 
If a subject’s treatment is discontinued by the investigator or the subject because of an AE, that 
AE should be indicated as the reason for treatment discontinuation. All subjects will be 
encouraged to remain in the study and to complete all required study visits throughout the 24-
week study duration. 
If a subject achieves complete clearance at Week 12 or before and experiences new lesions 
between Week 12 and Week 24, an AE of molluscum contagiosum should be documented to 
capture this recurrence since there is no lesion count after Week 12. 
See Section 9 for additional information regarding adverse events. 
8 
STUDY DRUG TREATMENT 
8.1 
Description of Products 
Study drug treatment will include once daily application of SB206 10.3% or Vehicle (placebo) 
gel. Each dose will consist of berdazimer gel or vehicle gel that will need to be mixed with 


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hydrogel on a supplied dosing guide, and then immediately applied by the subject or caregiver to 
the affected designated area(s). 
All study drug treatments will be manufactured and provided by the sponsor. The study 
treatments and their attributes are described in Table 7. 
Table 7 
Study Drug 
 
SB206 10.3%  
Vehicle gel 
Study Drug Components 
Berdazimer gel 22.7% and buffered 
hydrogel  
Mixed immediately prior to application 
Vehicle gel and buffered hydrogel  
Mixed immediately prior to application 
Name of Active Ingredient 
Berdazimer Sodium 
None 
Packaging 
One kit will include 3 x 14g aluminum 
tubes of berdazimer gel and 3 x 14g 
aluminum tubes of hydrogel  
One kit will include 3 x 14g aluminum 
tubes of vehicle gel and 3 x 14g 
aluminum tubes of hydrogel  
Storage Requirements 
Refrigerated, horizontal 
2-8°C until dispensed 
Refrigerated, horizontal  
2-8°C until dispensed 
Appearance Post-Mixing 
Opaque white gel 
Opaque white gel 
Dosing Schedule 
QD 
QD 
Route of Administration 
Topical Application 
Topical Application 
Note that description of the concentration of SB products used nominal numbers based on percent berdazimer 
sodium historically. Novan has updated the naming convention to use percent berdazimer. Therefore, SB206 12% 
(nominal berdazimer sodium) is the same admixture formulation as SB206 10.3% (berdazimer). In this protocol, 
the nominal berdazimer sodium numbers remain in historical studies.  
8.1.1 
Formulation, Storage, Preparation, and Handling 
SB206 is a two-component drug product formulation intended for topical administration. The 
drug product is comprised of an active gel component containing the berdazimer sodium drug 
substance, and a buffered hydrogel (aqueous) component that when mixed releases nitric oxide. 
Berdazimer sodium is silsesquioxanes, 3-(2-hydroxy-1-methyl-2-nitrosohydrazinyl)propyl 3-
(methylamino)propyl, polymers with silicic acid (H4SiO4) tetra-Et ester, hydroxy-terminated, 
sodium salts. 


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Figure 4 
Structure of Berdazimer Sodium (active ingredient in SB206) 
 
8.2 
Dosing and Administration 
During the double-blind treatment period, study drug will be assigned using an IWRS. 
Approximately 850 subjects, 6 months of age and older, with a minimum of 3 and a maximum of 
70 lesions at Baseline will be randomized. A drug kit consisting of 6 tubes of assigned study 
drug sufficient for 4 weeks of dosing will be dispensed to the subject at the Baseline Day 1 visit. 
A second kit will be dispensed at Week 4, and a third kit will be dispensed at Week 8. Three of 
the tubes will contain berdazimer gel or vehicle gel and 3 of the tubes will contain buffered 
hydrogel. When the gel and hydrogel are mixed together, the components form a gel that will be 
applied to the lesions. If a subject’s lesions have been confirmed by an investigator as completely 
cleared at Weeks 4 or 8, a new kit should still be dispensed so that the subject can resume once 
daily treatment in the event of recurrence or new lesions prior to the next scheduled visit. 
The first study drug dose will occur on Baseline Day 1, with application by the subject or 
caregiver following training by the site. Subsequent applications of study drug occur at home or 
on-site at the clinic visits at Week 2, Week 4 (if the visit is performed in clinic), Week 8, and 
Week 12. Subjects will return their kit to each clinic visit for weight and retraining purposes; at 
Week 2 only, the kit will be re-dispensed to the subject.  
The following is a summary of the subject’s/caregiver’s role in treatment of lesions:  
• Continuous daily treatment of treatable lesions to Week 4 at a minimum 
• Continued treatment of treatable lesions after Week 4 unless otherwise instructed by the 
Investigator 
• Self-initiated treatment of new or recurrent lesions  
• Documentation of daily dose application in subject diary 


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Withdrawal and discontinuation are covered in Section 6.8. 
8.3 
Treatment Allocation 
Subjects will be randomly assigned in a 1:1 fashion to either SB206 10.3% or Vehicle gel.  
8.4 
Randomization Strategy and Procedure 
The randomization schedule will be computer generated using a permuted block algorithm and 
will randomly allocate IP to randomization numbers. As subjects qualify to be randomized into 
the study, a randomization number will be assigned through a central IWRS. At randomization, 
subjects will be stratified by investigator type (dermatologist vs. other), the subject’s BOTE 
score at Baseline (no inflammation (BOTE = 0) vs. mild/moderate/severe inflammation (BOTE 
≥ 1) and number of randomized subjects per household (1 subject per household vs. 2 subjects 
per household). Subjects will be stratified to 5 strata first by subjects per household. Subjects 
from 1 subject households will be stratified by investigator type and baseline BOTE score. 
Subjects from 2 subject households will not be further stratified with respect to investigator type 
and baseline BOTE score because the overall sample size that is expected for the stratum for 
households with two subjects is not large enough to support further stratification. Approximately 
850 subjects, 6 months of age and older, with a minimum of 3 and a maximum of 70 lesions at 
Baseline will be randomized.  
8.5 
Extent and Maintenance of Blinding 
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.  
Study personnel will endeavor to safeguard the integrity of the study blind to minimize bias in 
the conduct of the study.  
8.5.1 
Unblinding Procedures 
8.5.1.1 
Planned Unblinding 
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 CRO 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 eCRF for 


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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. 
Of note, all available unblinded safety data will be provided to the DSMB to review after 
approximately 200 subjects are randomized. Personnel who are not otherwise involved in the 
study will prepare the unblinded data and summary tables for this analysis.  
8.5.1.2 
Unplanned or Unintentional Unblinding 
All instances of unplanned or unintentional unblinding will be documented. 
8.6 
Assessment and Verification of Compliance 
Subjects will be provided a diary to record doses taken on a daily basis. The diary will contain a 
reminder for subjects to not administer their dose the day of each visit. Review of subject 
compliance with the diary completion and dosing will be conducted at each visit. Subject 
compliance will be based on calculation from the missed doses recorded from the subject diary 
and from additional information noted in the source (e.g. investigator instructed interrupted or 
modified doses).  
8.7 
Prior and Concomitant Therapies 
At Screening, prior MC medications/therapies taken within 6 months of Screening will be 
recorded. Subjects receiving medicinal treatment or other therapy for MC as defined in the study 
Exclusion Criterion #4, 5, or 6 at the time of the Screening Visit may enter a washout period of 
up to 14 days prior to the Baseline visit. Subjects receiving or that have received an 
investigational drug/device within 14 days or 5 half-lives (whichever is longer) prior to Baseline 
as described in Exclusion Criterion #13 may enter a washout period of up to 14 days prior to the 
Baseline visit (Section 5.2). 
Initiation of new medications and changes to ongoing medications will be reviewed and 
documented at each study visit from Screening through Week 24, as well as at Unscheduled Visits. 
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. 


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Clinically significant LSRs (e.g., those that interfere with a subject’s normal daily activities) that 
are reported as adverse events and/or subject reported intolerability (i.e. itching, pain) may result 
in an investigator directed temporary treatment hold (drug holiday), and topical corticosteroids 
may be used to treat LSRs for up to 2 weeks. The subject may re-initiate study drug treatment 
prior to the next scheduled visit. Upon re-initiation (challenge) of study drug treatment, if a 
subject develops worsening LSRs, allergic contact dermatitis may be suspected. In the event of 
suspected allergic contact dermatitis, the investigator will discontinue the subject from study 
drug treatment and treat the area(s) with corticosteroids for up to 2 weeks. If the subject provides 
consent/assent, the investigator will consult the CRO medical monitor to implement the process 
for patch testing 
8.7.1 
Prohibited Therapies 
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 over-the-counter 
products including, but not limited to, ZymaDerm and tea tree oil, cimetidine and other 
histamine H2 receptor antagonists. Surgical procedures to treat MC (e.g. cryotherapy, curettage) 
are prohibited during the study. The CRO medical monitor should be contacted for any questions 
regarding prohibited therapies. 
9 
SAFETY MONITORING 
Adverse events will be assessed and collected after the initiation of study drug treatment through 
the end of the subject’s last visit. 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?” 
SAEs will be collected from the time of consent through the end of the subject’s last visit. 
Adverse events that occur from time of consent up to the time of treatment administration should 
be recorded as medical history for all participants. Serious adverse events will be followed until 
resolution. 
9.1 
Definitions 
• Adverse event – An AE is any untoward medical occurrence associated with the use of an 
intervention in humans whether or not it is considered intervention-related. 
• Serious adverse event (SAE) – An event is considered “serious” if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
− Death 
− A life-threatening AE (An event is considered “life-threatening” if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at 


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immediate risk of death. It does not include an AE or suspected adverse reaction (AR) 
that, had it occurred in a more severe form, might have caused death.) 
− Inpatient hospitalization or prolongation of existing hospitalization 
− A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
− A congenital anomaly/birth defect 
− Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
• Causality or relatedness – Determination of whether there is a reasonable possibility that 
the product is causally related to the adverse event. Causality assessment includes, for 
example, evaluation of temporal relationships, dechallenge/rechallenge information, 
association with (or lack of association with) underlying disease, presence (or absence) of 
a more likely cause, and biologic plausibility.  
• Adverse reaction – An AR is any AE caused by a drug. 
• Suspected adverse reaction (SAR) – An SAR is any AE for which there is a reasonable 
possibility that the drug caused the AE. For the purposes of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal relationship between 
the drug and the AE. SAR implies a lesser degree of certainty about causality than AR. 
• Unexpected – An event is considered unexpected if it is not listed in the IB, is not listed 
at the specificity or severity that has been observed, or, if an IB is not required or 
available, is not consistent with the risk information described in the General 
Investigational Plan or elsewhere in the IND. Unexpected also refers to events that are 
mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug but are not specifically mentioned as occurring 
with the particular drug under investigation. 
9.2 
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 no later than 5 days of the site’s first knowledge. 
The site must report all SAEs to the CRO within 24 hours after first knowledge of the event by 
the study site. The date of onset, date ended, accurate event term, seriousness, severity, outcome, 
causality (relationship to study drug), therapy required, and action taken regarding study drug 
and study participation will be reported for each AE. 


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Significant LSRs (as judged by the investigator), scarring, and hypertrophic/keloid scars will be 
captured as adverse events. 
9.2.1 
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  
9.2.2 
Assessment of Causality 
Several factors should be considered when assessing the relationship (causality) of an event to 
the study drug or administration of the study drug. The investigator should assess the relatedness 
to the study drug using a standard of a reasonable possibility of a causal relationship between the 
study drug and the AE, as per the examples in Table 8: 
Table 8 
Assessment of Causality 
Related Events:  
Include those assessed 
as definitely, possibly, 
or probably related 
events 
• Reasonable temporal sequence to drug administration 
• Event can be fully attributable to administration of the study drug 
• Known pharmacological action of the study drug 
• Specific tests available (positive allergy test, antibodies, metabolites) 
• As adverse drug reaction in the product information (Investigator’s Brochure) 
• Reported in the literature as a possible side effect 
• Dechallenge (event abates on discontinuation of the study drug/without treatment) 
• Rechallenge positive (event reappears on re-exposure to study drug) 
• Not explained otherwise by the subject’s clinical state or medical history or by other 
concomitant agents/therapies, etc.  
Unrelated Events:  
Include those assessed 
as unlikely or 
unrelated events 
• No reasonable temporal sequence to study drug administration 
• Event is explained by a number of other factors such as a subject’s clinical state, 
medical history, or other concomitant agents/therapies 
• Etiology has been clarified and is in no way related to the study drug 
• No reason for suspecting a causal relationship to the study drug and 
• Investigators have established this beyond reasonable doubt 
 
9.2.3 
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/ 


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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 the appropriate reporting form to 
the CRO 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. 
7. 
The investigator is responsible for following pregnancies through the end of the pregnancy 
and for providing the assessment of the healthy live birth or for reporting any abnormal 
pregnancy outcome such as stillbirth, miscarriage, or deformity to the CRO/sponsor. 
For clarity on how to record an adverse event that progresses into a serious adverse event, there 
should be two events recorded: the first event would be the beginning adverse event, and the 
second event would be the serious adverse event (i.e. only the time the AE qualified as serious). 
Resolution of the SAE should be recorded in the same manner, two end dates for SAE and AE, 
where the SAE and AE may or may not share the same end date.  
9.3 
Adverse Event Follow-up 
AEs that are not resolved at the time of the last scheduled study visit (Week 24/ET2) must be 
recorded in the study database as ongoing/not recovered/not resolved/resolving. Treatment 
related adverse events and serious adverse events, including LSRs and scars/keloids, will be 
followed until resolution or up to 1 year after last treatment, whichever is sooner. 


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The investigator should follow all SAEs until the events are resolved, or the subject completes 
study participation at Week 24/ET2. 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. 
9.4 
Women of Childbearing Potential & Pregnancy 
A female is considered of childbearing potential if she has reached 9 years of age or unless she is 
post-menopausal (no menses for 12 consecutive months), surgically sterilized (documented 
hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy). Tubal 
ligation does not meet the definition of surgically sterile. 
WOCBP must use an effective method of birth control during the study. The following are 
considered acceptable methods of birth control for this study: hormonal contraceptives 
(combined estrogen and progestogen or progestogen only, including oral, injectable, transdermal 
or injectable formulations); intrauterine device (IUD); intrauterine hormone releasing system 
(IUS); bilateral tubal occlusion or ligation if performed ≥ 3 months prior to Baseline; same sex 
partner or partner who has had a vasectomy; sexual abstinence .with a documented acceptable 
method of birth control if the subject becomes sexually active; female or male condoms with or 
without spermicide; or a cervical cap, diaphragm, or sponge with spermicide. Women with tubal 
occlusion or ligations or whose partner has had a vasectomy will be required to complete UPTs 
at the required timepoints if the procedure was done < 3 months prior to Baseline. 
Before enrolling any subject in this clinical trial, the investigator must review guidelines about 
study participation including the topics below: 
• Informed consent document 
• Pregnancy prevention information 
• 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. 
During the study, females who have reached the age of menarche should be instructed to contact 
the investigator immediately if they suspect they might be pregnant (e.g., missed or late 


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menstrual cycle). Study drug shall be held immediately if a subject is suspected to be pregnant 
and study drug must be permanently discontinued if pregnancy is confirmed. The investigator 
must immediately notify the medical monitor/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 will be 
discontinued from study drug treatment, continue with study visits through Week 24 and follow 
up with pregnancy outcome. The site should follow-up with the subject periodically during the 
pregnancy for ongoing health and safety information through the end of the pregnancy, as 
applicable. The investigator is responsible for following the pregnancy through the end of the 
pregnancy and for providing the assessment of the healthy live birth or for reporting any 
abnormal outcome such as stillbirth, miscarriage, or deformity to the CRO/sponsor (Note: 
Congenital anomalies  are considered SAEs and require separate reporting per Section 9.2.3). 
9.5 
Overdose or Misuse 
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. The 
medical monitor/CRO/sponsor must be notified of any subject exhibiting signs of 
methemoglobinemia. 
10 
ANALYSIS 
10.1 
Hypothesis 
This study is intended to formally evaluate the efficacy of SB206 10.3% QD against Vehicle.  
The primary efficacy comparison will test the following hypotheses: 
H0: The proportion of subjects with complete clearance is equal between SB206 10.3% 
QD and Vehicle; 
H1: The proportion of subjects with complete clearance is different between SB206 
10.3% QD and Vehicle.  
10.2 
Population 
10.2.1 
Sample Size Rationale 
Approximately 850 subjects, 6 months of age and older, with a minimum of 3 and a maximum of 
70 MC lesions at Baseline will be randomized in a 1:1 (active:vehicle) scheme. The sample size 
assumptions for this study were informed by the integration of the completed phase 3 studies 
NI-MC301 and NI-MC302. Multiple replications of simulated random sampling of the integrated 
NI-MC301 and NI-MC302 data was performed to ensure the sample size assumptions align with 
the proposed design of NI-MC304. This includes the 1:1 ratio (active:vehicle) and the 
percentages observed in NI-MC301 and NI-MC302 for each stratum of each of the stratification 


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factors: investigator type, number of randomized subjects per household, and baseline BOTE 
score that are planned for NI-MC304. 
The analysis of the proportion of subjects with complete response of all treatable MC at Week 12 
within the Intent-to-Treat (ITT) Population of the multiple replications of simulated random 
sampled integrated data yields rates of 20% for vehicle and 29.5% for SB206 10.3% QD with the 
covariate-adjusted treatment difference was 9.5%. A sample size of 850 subjects (425 subjects in 
the SB206 10.3% QD group and 425 subjects in the vehicle group) will provide 90% power for a 
2-sided alpha test of size 0.05 to detect an absolute difference of 9.5% when the vehicle response 
rate is 20%.    
10.2.2 
Analysis Subsets 
The Intent-to-Treat (ITT) analysis population will include all randomized subjects who have a 
signed informed consent or assent as applicable. The ITT analysis population will be used as the 
main analysis population for efficacy (primary and secondary) and exploratory endpoints. 
Subjects will be analyzed according to the treatment group to which they were randomized. 
The Per Protocol (PP) analysis population will include all ITT subjects with no significant 
protocol deviations potentially having an impact on the efficacy evaluations. Subjects will be 
analyzed according to the treatment group to which they were randomized. The PP analysis 
population will be used as a supportive analysis population for the primary and secondary 
efficacy endpoints. 
The Safety analysis population will include all ITT subjects who received at least one dose of the 
study treatment. Subjects will be analyzed according to the study treatment actually received. 
The Safety analysis set will be used for the summary of demographic and other baseline 
characteristics, prior and concomitant medications, exposure and compliance with the study 
drug, and all safety endpoints.  
10.2.3 
General Considerations 
Continuous variables will be summarized by treatment group and visit, when applicable, using 
the number of subjects with non-missing data (n), mean, standard deviation (SD), median, 
minimum, and maximum. Categorical variables will be summarized by treatment group and 
visit, when applicable, using frequencies and percentages. 
All statistical tests will be two-sided and will be performed with a significance level of 0.05, 
unless otherwise specified. 
Additional details regarding the analysis of primary, secondary, exploratory, safety endpoints 
and all sensitivity analysis will be included in the SAP. The SAP will be finalized before 
unblinding and database lock. 


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10.3 
Testing Procedures 
10.3.1 
Analysis of the Primary Efficacy Endpoint 
The primary efficacy endpoint for this study is the proportion of subjects achieving complete 
clearance of all treatable molluscum lesions at Week 12 for the ITT population. Complete 
clearance of all MC at Week 12 is defined as having a lesion count of 0 at Week 12. The number 
and percentage of subjects with complete clearance at Week 12 will be summarized by treatment 
group.  
The primary efficacy endpoint will be analyzed using a generalized estimating equation (GEE) 
for logistic regression with an exchangeable working correlation structure. The model will 
include treatment, investigator type (dermatologist vs other), Baseline BOTE score (no 
inflammation (BOTE = 0) vs. mild/moderate/severe inflammation (BOTE ≥ 1) and number of 
randomized subjects per household (1 subject per household vs. 2 subjects per household), age 
and Baseline lesion count as factors. The odds ratio between SB206 10.3% and vehicle gel, 95% 
CIs for the odds ratio, and P-value for the covariate-adjusted treatment comparison will be 
presented; together with predicted proportions along with their associated 95% confidence 
interval. Only subjects who achieve complete clearance at Week 12 will be counted as 
responders for the primary analysis. Subjects who discontinue the study before the Week 12 
analysis visit for any reason will be considered not to have achieved complete clearance at Week 
12, even if the subject discontinues after a lesion count of 0. 
As a sensitivity analysis, the primary efficacy analysis will also be applied to the PP population. 
Additional sensitivity analyses may be performed including analyses that utilize alternative 
assumptions from those of this primary method to ensure that efficacy results are not driven by 
the method of handling missing data.  
10.3.2 
Analysis of Secondary Efficacy Endpoints 
The familywise error rate with respect to the primary endpoint and secondary endpoints will be 
strongly controlled at the alpha=0.05 level using a hierarchical fixed sequence method testing 
strategy. If the primary endpoint is not statistically significant at the alpha=0.05 level, the 
secondary efficacy endpoints will be considered not significant. If the primary endpoint is 
statistically significant at the alpha=0.05 level, the secondary efficacy endpoints will be tested in 
the following hierarchical fixed sequence: 
• Proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at Week 12 
• Proportion of subjects achieving at least a 90% reduction from Baseline in the number of 
all treatable MC at Week 12 
• Proportion of subjects with complete clearance of all treatable MC at Week 8 
• Percent change from Baseline in the number of all treatable MC at Week 4 
At each subsequent test of the secondary efficacy endpoints, if the secondary endpoint is not 
statistically significant at the alpha=0.05 level, the remaining secondary efficacy endpoints will 


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be considered not significant. If the secondary endpoint is statistically significant at the 
alpha=0.05 level, the next subsequent secondary efficacy endpoint will be tested following the 
sequence. 
10.3.3 
Population Analysis 
10.3.3.1 
Disposition 
Subject disposition information will be summarized for all subjects by treatment group. 
Summaries will include: the number of subjects screened, the number of subjects in each 
analysis population, the number of subjects where study treatment stopped, primary reason for 
study treatment stopped, the number of subjects completing 12 weeks of the study, the number of 
subjects completed the study, and the primary reason for discontinuation. 
10.3.3.2 
Demographics and Baseline Characteristics 
Demographic variables include age, sex, ethnicity, and race. Age will be calculated in years 
relative to the informed consent date.  
Other baseline characteristics include lesion counts at baseline, baseline BOTE score, site type 
(dermatologist vs other), and age at and time since onset of symptoms of current molluscum 
episode. Demographic and baseline characteristics will be summarized for the Safety, ITT, and 
PP Populations. 
10.3.4 
Safety Analysis 
No missing safety data will be imputed, and no inferential statistics will be done for any safety 
endpoints. Change from Baseline in abbreviated physical examinations and a summary of 
concomitant medications will be presented. 
10.3.4.1 
Adverse Events 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA 
Version 23.0 or later). 
A treatment-emergent AE (TEAE) is defined as those AEs that occurred any time on or after the 
first in-clinical application of study drug through the last application of study drug and those 
existing AEs that worsened during this same period. If it cannot be determined whether the AE is 
treatment emergent due to a partial onset date, then it will be counted as such. 
TEAEs will be summarized by System Organ Class (SOC) and Preferred Term (PT). For the 
summary by SOC and PT, each subject will be counted only once within a SOC or a PT. AEs 
with an outcome of death, SAEs, TEAEs leading to discontinuation from study treatment, and 
TEAEs leading to discontinuation from the study will be summarized similarly. 
TEAEs will be further summarized by worst severity and highest relationship with study 
treatment, separately. For the summary by worst severity, each subject will be counted only once 


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within a SOC or PT according to the worst reported severity. Similarly, for the summary by 
highest relationship with study treatment, each subject will be counted only once within a SOC 
or PT according to the highest reported relationship with study treatment. 
Separate listings will be provided for the AEs with an outcome of death, SAEs, TEAEs leading 
to discontinuation from study treatment, and TEAEs leading to discontinuation from study. 
The proportion of subjects with scarring and the proportion of subjects with keloid or 
hypertrophic scarring will be summarized descriptively. 
10.3.4.2 
Local Skin Reactions 
The LSR composite score will be calculated by summing up all the numerical responses (0-4) to 
each individual parameter for a composite score that ranges between 0 and 24. The change from 
Baseline of the LSR composite score will be summarized descriptively. A table summarizing 
each LSR parameter (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and 
erosion/ulceration) score at each scheduled postbaseline assessment will be presented. 
Additionally, a shift table comparing the baseline score for each LSR parameter to each 
scheduled postbaseline assessment will be presented for the Safety Population. 
10.3.5 
Other Analyses 
A shift table comparing the baseline BOTE score to each scheduled post-baseline assessment 
will be presented for the Safety Population. Additional BOTE vs lesion count/complete clearance 
analyses may be explored and further detailed in the SAP. 
10.3.6 
Exploratory Analysis 
The exploratory endpoints based on the proportion of subjects achieving complete clearance (at 
Weeks 2, 4) or 75% (at Weeks 2, 4, 8, 12), 90% (at Weeks 2, 4, 8) reductions will be analyzed in 
the same manner as the primary endpoint.  
Likewise, the proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at 
Weeks 2, 4 and 8 will be analyzed in the same manner as the primary endpoint. 
The change and percent change from Baseline in the number of treatable MC will be analyzed 
using a repeated measures mixed model for the respective visits with the same covariates as the 
primary model together with visits and treatment by visit.  
Time to first complete clearance of all MC will be analyzed using Kaplan-Meier methods. The 
number and percentage of subjects achieving complete clearance, number and percentage of 
censored subjects, and Kaplan-Meier estimates of first quartile, median, and third quartile will be 
summarized by treatment group.  
The proportion of subjects who have a recurrence of MC after the first visit at which complete 
clearance was observed will be summarized. 


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The subject-reported spread of MC to household members not in the study will be summarized 
descriptively including a breakdown of whether or not there was any spread and then a 
breakdown of the amount of spread within the household at each visit at the household level. 
Investigator global severity assessment and investigator global impression of change will be 
summarized descriptively. Subject global severity assessment and subject global impression of 
change will be summarized descriptively.  
Listings will be provided for the results from the study exit interview. 
11 
ETHICAL CONSIDERATIONS 
11.1 
Good Clinical Practice 
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry 
E6 (R2) 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/her knowledge, it 
accurately describes the conduct and results of the study. 
11.2 
Data Safety Monitoring Board (DSMB) 
When approximately 200 subjects are randomized, a Data Safety Monitoring Board (DSMB) 
will review all available unblinded safety data (including completed patch testing results). The 
DSMB will provide their recommendation for the study to proceed or not proceed. 
11.3 
Ethics Review  
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. 
11.4 
Informed Consent 
In compliance with 21 C.F.R. § 50.25, 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. This study may include both paper-based informed consent/assent forms, and 
electronic consent/assent forms. All consent/assent forms will be 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 


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terms suited to the subject’s comprehension of the purposes, procedures, and potential risks of 
the study, alternative treatment options, 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 
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. 
11.5 
Data Privacy 
Pursuant to 21 CFR, all information, including images and remote visits via video and telephone, 
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 documented consent is gained from 
Novan. However, authorized regulatory officials, IRB/IEC personnel, Novan and its authorized 
representatives are allowed full access to the records. 
Subjects 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. 
11.6 
Disclosure 
The study will be posted to clinicaltrials.gov. 
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. 
12 
OVERSIGHT 
12.1 
Quality Control and Assurance 
12.1.1 
Monitoring 
All aspects of the study will be monitored by the CRO or Novan according to GCP and Standard 
Operating Procedures (SOPs) for compliance with applicable government regulations, (i.e., 
informed consent regulations, (21 CFR § 50.20, 1999), and Institutional Review Board 
regulations, (21 CFR § 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 


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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 CFR § 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 be in regular contact with the site and will perform 
remote visits and on-site visits in accordance with the monitoring plan. The objective of these 
communications is to review 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 site. Monitoring standards require full verification for 
the presence of informed consent, adherence to the inclusion/exclusion criteria, documentation 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 responsible IRB with a study summary shortly after study 
completion, as per IRB requirements. 
This study may incorporate the use of remote monitoring and on-site monitoring visits based on 
many factors. Risk based monitoring may also be utilized to focus on oversight of subject safety 
and data integrity. Additional details regarding these visits can be found in the clinical 
monitoring plan.  


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12.1.2 
Audits 
In addition to the routine monitoring procedures, audits of clinical research activities in 
accordance with 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, study 
drug, original, study-relevant medical records). All subject data will be treated confidentially. 
12.1.3 
Protocol Modification/Deviations 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the sponsor. All protocol modifications should be submitted to the IRB in the form 
of an amendment, with approval obtained prior to implementation of changes unless the 
amendment is intended to reduce immediate subject risk. When the protocol modification 
substantially changes the protocol design or updates the potential study risks section of the 
Informed Consent Form, the Informed Consent Form will be amended/approved by the IRB, 
requiring all subjects already enrolled to provide informed consent, again. 
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. This will allow an early joint decision regarding the subject’s continuation 
in the study. All deviations, as well as subject participations decisions, will be documented by 
the investigator and the CRO.  
If additional contingency measures that require deviation from the protocol are enacted, efforts 
will be made to minimize impacts on trial integrity, and to document the reasons for protocol 
deviations as outlined in the clinical trial continuity plan. 
12.1.4 
Records  
12.1.4.1 
Data Capture and Management 
Subject data will be entered into a sponsor-approved electronic database compliant with 21 CRF 
Part 11, into electronic case report forms (eCRFs) and combined with data provided from other 
sources (e.g., laboratory) in validated datasets then transmitted electronically to the sponsor or 
designee. Management of clinical data will be performed in accordance with the applicable 


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sponsor-approved standards and data cleaning processes to ensure the integrity of the data. A 
data management plan for the study will be maintained by the CRO. 
Adverse events and prior/concomitant medications and medical history terms will be coded using 
the most current versions of MedDRA and the World Health Drug Dictionary (WHODrug), 
respectively. 
The investigator will retain original source documents and the sponsor will receive eCRF-
required data as electronic datasets. Subject initials will not be collected or transmitted to the 
sponsor. 
12.1.4.2 
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 eCRF 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. 
12.1.4.3 
Study Files and Records 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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12.2 
Study Termination or Study Site Closure 
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. 
13 
PUBLICATION POLICY 
Novan is responsible for preparing and providing the appropriate regulatory authorities with 
clinical study reports according to the applicable regulatory requirements. 
Novan’s publication policy is discussed in the investigator's Clinical Study Agreement. 


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14 
REFERENCES 
Chen et al., 2013 
Chen X, Anstey A, Bugert J.  Molluscum contagiosum virus infection.  Lancet Infect Dis. 
2013 Oct;13(10):877-88. 
Dohil et al., 2006 
Dohil MA, Lin P, Lee J, et al. The epidemiology of molluscum contagiosum in children. 
J Am Acad Dermatol. 2006 Jan;54(1):47-54.  
FDA, 2020 
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 
Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review 
Boards. 2020 Apr 16 
Olsen et al., 2015 
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(2):190-5/ 
Olsen et al., 2014 
Olsen J, Gallacher J, Piguet V, et al.  Epidemiology of molluscum contagiosum in 
children: a systematic review.  Fam Pract. 2014 Apr;31(2):130-6. 
Osio et al., 2011 
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. 
Schofield et al., 2011 
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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APPENDIX 1 
PROCEDURE FOR SUSPECTED SENSITIZATION 
After treatment is reintroduced post-LSR, if a subject experiences a stronger LSR (second LSR 
event) than the first LSR event, allergic contact dermatitis may be suspected. In order to confirm 
whether the reaction is allergic contact dermatitis, patch testing should be conducted. If the 
investigator determines that patch testing is appropriate and the patient/caregiver consent to 
patch testing, he/she should contact the CRO medical monitor to discuss. Once the LSR has been 
completely resolved for a period of 2 weeks and up to 2 months, patch testing may commence. 
Novan will provide more detailed patch testing instructions once requested from the CRO 
medical monitor. The site will use a study drug kit already assigned to the subject in order to 
complete the testing. Additional drug product for patch testing may be supplied through IWRS if 
the currently assigned subject’s investigational product was assigned more than 60 days prior to 
the patch testing date(s) or if the subject had previously returned all their drug product. 
For patch testing: 
• Discontinue study treatment (see Section 7.2.3 regarding LSRs) 
• Document the event as an AE and consult with the CRO medical monitor. Detailed 
instructions for the patch testing will be provided after discussion with the medical 
monitor. 
• When applicable, challenge patch testing should be performed after all signs and 
symptoms of the LSR have been resolved for approximately 2 weeks to 2 months. 
• The randomized study treatment will be applied to a naïve area on the participant’s back 
or arm. Use the subject’s most recently assigned study drug kit to obtain material for 
testing. 
• The participant will return to the site approximately 48 hours after the application of the 
patches. Approximately 30 minutes, 24 hours and 48 hours after patch removal, the patch 
site(s) will be evaluated using the scale in Table 9. If the 48-hour reading is equivocal, it 
is recommended to evaluate the site at 72 to 96 hours after removal. Take photographs at 
every time point and transmit them to the medical monitor. Further instructions will be 
given after review of the photos. 
• At the last reading, the investigator will make the final interpretation of any challenge 
reactions. This last reading (at least 48 hours after patch removal) is critically important 
to distinguish irritant reactions (which fade) from true allergic reactions (which persist) 
and to identify allergic reactions that do not appear at the time of patch removal. See 
Table 10. 
 


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Table 9 
Grading System for Patch Test Reactions (at each time 
point) 
Score 
Description 
+/- 
Doubtful reaction, faint macular erythema 
+ 
Weak, non-vesicular reaction with erythema, infiltration, and papules 
++ 
Strong vesicular reaction with erythema, infiltration, and papules 
+++ 
Spreading bullous reaction 
- 
Negative reaction 
IR 
Irritant reaction 
 
Table 10 
Challenge Reaction Interpretation (based on the last 
reading (at least 48 hours after patch removal) 
Score 
Description 
Negative 
Might include an irritative reaction 
Equivocal 
Unable to determine 
Positive* 
Reaction definitely due to sensitization 
 
*Judgement of “positive” reaction should be accompanied by ++ or greater reading at the last 
reading. 

SAP_001.pdf: 
 
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Novan NI-MC304 SAP Version 2 
 
 
 
Statistical Analysis Plan 
 
Novan, Inc.  
NI-MC304 
 
A Phase 3 Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, Parallel Group 
Study Comparing the Efficacy and Safety of SB206 and Vehicle Gel Once Daily in the 
Treatment of Molluscum Contagiosum 
Protocol Version: 30Sep2020 
 
 
 
Sponsor:  
 
Novan, Inc.  
4105 Hopson Road 
Suite 146 
Morrisville, NC 27560 
 
 
Prepared by:  
Christopher Tait 
5909 Sea Otter Place, Suite 100 
Carlsbad, CA 92010 
 
 
Version 
Date 
Version 1 
01 Oct 2020 
Version 2 
24 May 2021 
 
 
 
 
 


 
 
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NI-MC304 
 
24May2021 
 
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Novan NI-MC304 SAP Version 2 
Approval 
 
Upon review of this document, including the table, listing, and figure shells, the undersigned 
approves the statistical analysis plan. The analysis methods and data presentation are acceptable. 
 
 
Signature 
Date 
 
 
_______________________________________________ 
Christopher Tait, PhD 
Principal Biostatistician 
Synteract 
 
 
 
 
 
_______________ 
 
 
_______________________________________________ 
David Hebert, PhD 
Senior Director, Head of Biometrics 
Novan, Inc. 
 
 
 
 
 
_______________ 
 
 
 


 
 
Novan, Inc.  
 
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NI-MC304 
 
24May2021 
 
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Novan NI-MC304 SAP Version 2 
TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS ....................................................................................................... 5 
1. 
INTRODUCTION .................................................................................................................. 6 
2. 
STUDY DOCUMENTS ......................................................................................................... 6 
3. 
STUDY OBJECTIVES .......................................................................................................... 6 
4. 
STUDY DESIGN AND PLAN .............................................................................................. 6 
5. 
DETERMINATION OF SAMPLE SIZE .......................................................................... 10 
6. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................. 11 
7. 
NOTATION OF TREATMENT GROUPS AND VISITS ............................................... 12 
8. 
ANALYSIS POPULATIONS .............................................................................................. 13 
9. 
STUDY POPULATION....................................................................................................... 14 
9.1 
SUBJECT DISPOSITION .................................................................................................. 14 
9.2 
ELIGIBILITY.................................................................................................................. 14 
9.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ..................................................... 14 
9.4 
EXTENT OF EXPOSURE ................................................................................................. 14 
9.5 
PROTOCOL DEVIATIONS .............................................................................................. 15 
9.6 
MEDICAL HISTORY ...................................................................................................... 16 
9.7 
PRIOR AND CONCOMITANT MEDICATIONS .................................................................. 16 
10. EFFICACY ANALYSES ..................................................................................................... 16 
10.1 EFFICACY ENDPOINTS .................................................................................................. 17 
10.2 BASELINE VALUES ....................................................................................................... 18 
10.3 ADJUSTMENTS FOR COVARIATES ................................................................................ 18 
10.4 HANDLING OF DROPOUTS OR MISSING DATA ............................................................. 18 
10.5 INTERIM ANALYSIS AND DATA MONITORING ............................................................. 19 
10.6 EXAMINATION OF SUBGROUPS .................................................................................... 19 
10.7 MULTIPLE COMPARISON/MULTIPLICITY ..................................................................... 20 
10.8 MULTICENTER STUDIES ............................................................................................... 20 
11. METHODS OF EFFICACY ANALYSIS .......................................................................... 21 
11.1 PRIMARY EFFICACY ANALYSIS ................................................................................... 21 
11.2 SECONDARY EFFICACY ANALYSES ............................................................................. 23 
11.3 EXPLORATORY ANALYSES .......................................................................................... 24 
12. OTHER ANALYSES ........................................................................................................... 25 
13. SAFETY ANALYSES .......................................................................................................... 26 
13.1 ADVERSE EVENTS ........................................................................................................ 26 
13.2 LOCAL SKIN REACTION ............................................................................................... 27 
13.3 EVENTS OF SPECIAL INTEREST .................................................................................... 28 
13.4 URINE PREGNANCY TEST ............................................................................................ 28 
13.5 PHYSICAL EXAMINATION ............................................................................................ 28 
13.6 PATCH TESTING ........................................................................................................... 28 
14. CHANGES TO PROTOCOL-SPECIFIED ANALYSES ................................................ 28 
15. REFERENCES ..................................................................................................................... 29 


 
 
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24May2021 
 
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Novan NI-MC304 SAP Version 2 
APPENDIX A: PRESENTATION OF DATA AND PROGRAMMING SPECIFICATIONS .................... 30 
APPENDIX B: SAS PROGRAMMING QC REQUIREMENTS ....................................................... 34 
APPENDIX C:  LIST OF TABLES, FIGURES, AND LISTINGS ...................................................... 35 


 
 
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Novan NI-MC304 SAP Version 2 
LIST OF ABBREVIATIONS 
Abbreviation 
Full Notation 
AE 
adverse event 
ATC 
anatomical/therapeutic/chemical 
BOTE 
beginning of the end 
CRO 
contract research organization 
DSMB 
data safety monitoring board 
e-consent 
electronic consent 
eCRF 
electronic case report form 
ET 
early termination 
ICH 
International Council for Harmonisation 
ITT 
Intent-to-Treat 
LSR 
local skin reaction 
MC 
molluscum contagiosum 
MedDRA 
Medical Dictionary for Regulatory Activities 
PP 
Per-Protocol 
QC 
quality control 
QD 
once daily 
SAP 
statistical analysis plan 
TEAE 
treatment-emergent adverse event 
TLFs 
tables, listings, and figures 
 
  
 


 
 
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Novan NI-MC304 SAP Version 2 
1. INTRODUCTION 
This document outlines the statistical methods to be implemented during the analyses of data 
collected within the scope of Novan, Inc. protocol amendment 2 [A Phase 3 Multi-Center, 
Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study Comparing the Efficacy 
and Safety of SB206 and Vehicle Gel Once Daily in the Treatment of Molluscum Contagiosum]. 
The purpose of this plan is to provide specific guidelines from which the statistical analyses will 
proceed. Any deviations from this plan will be documented in the clinical study report. 
2. STUDY DOCUMENTS 
The following study documents are used for the preparation of the statistical analysis plan (SAP): 
• Protocol Amendment 2, 30Sep2020 
• Annotated electronic case report form (eCRF) version 1.0, 31Aug2020 
• Data management plan version 1.0, 12Aug2020 
3. STUDY OBJECTIVES 
The objective of the study is to evaluate the efficacy and safety of SB206 10.3% once daily (QD) 
for the treatment of molluscum contagiosum (MC). 
4. STUDY DESIGN AND PLAN 
In response to the recent COVID-19 pandemic, it is imperative to include additional protections 
to enhance the assurance of subject safety while protecting the integrity of the clinical trial data. 
In alignment with the FDA’s recommendation to utilize electronic and remote methods, the 
NI-MC304 study was designed to include electronic consent (e-consent) and remote technology 
for the study visits between Week 2 and Week 12, our primary endpoint, in an effort to minimize 
the amount of time that subjects and caregivers are required to be present in clinic, while also 
minimizing the number of contacts for our site personnel (FDA, 2020). Subjects/caregivers and 
investigators will practice at least one (simulated) remote assessment at the Baseline visit to 
familiarize each party with the technology before the first remote use. The frequency of planned 
on-site monitoring visits will be reduced, and more frequent remote monitoring visits will be 
incorporated to support protection of all team members. Enhanced central monitoring, telephone 
contact with the sites to review study procedures, trial participant status, and study progress, or 
remote monitoring of individual enrolled trial participants, will be performed as outlined in the 
monitoring plan. Additional information will be captured on any protocol deviations that occur 
due to COVID-19. Finally, a clinical trial continuity plan has been established for situations to 
outline the current modifications in case of further impact to the existing study design and plans. 
The plan incorporates contingency measures for additional disruptions due to COVID-19 and 
other unforeseen circumstances and provides a process for documenting any participants 
impacted by the circumstance and what was impacted. The SAP includes analyses that will be 


 
 
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performed to address the impact of the implemented contingency measures, and any necessary ad 
hoc analyses not incorporated into the SAP will be discussed in the clinical study report. 
 
This is a Phase 3 multi-center, randomized, double-blind, vehicle-controlled, parallel group study 
to be conducted in approximately 850 subjects with MC. After obtaining informed 
consent/assent, subjects who satisfy entry criteria will be randomized 1:1 (active:vehicle) using 
an interactive web response system. Subjects receiving current treatment for MC at the time of 
the Screening Visit will enter a washout period of up to 14 days prior to randomization. In the 
event no washout period is required, Screening and Baseline visit activities may be combined 
into a single in-clinic visit. At randomization, subjects will be stratified by investigator type 
(dermatologist vs other), the subject’s beginning-of-the end (BOTE) Inflammation Score at 
Baseline (no inflammation [BOTE=0] vs mild/moderate/severe/very severe inflammation 
[BOTE≥1]) and number of randomly assigned subjects per household (1 subject per household 
vs 2 subjects per household). Subjects will be stratified to 5 strata first by subjects per household. 
Subjects from 1-subject households will be stratified by investigator type and baseline BOTE 
score. Subjects from 2-subject households will not be further stratified with respect to 
investigator type and baseline BOTE score because the overall sample that is expected for the 
stratum for households with two subjects is not large enough to support further stratification.  
A maximum of two subjects from the same household may be randomized into the study. They 
must be randomized on the same day and both must individually meet all inclusion/no exclusion 
criteria. For subjects in the same household, Screening can occur on different days; however, the 
Baseline visit must occur on the same day. Households randomizing two subjects will receive the 
same treatment assignment for both subjects. 
Subjects or their caregivers will apply SB206 10.3% or Vehicle Gel once daily for a minimum of 
4 weeks and shall continue unless otherwise instructed by the investigator up to 12 weeks to all 
lesions identified at Baseline and new treatable lesions that arise during the course of the study. 
Subjects or their caregivers will continue to treat the area until the next scheduled visit even if 
the lesion(s) clear. At each in-clinic and remote visit, the investigator will count and record the 
number of active (raised, treatable) molluscum lesions per body area. Complete clearance should 
be confirmed by an in-clinic lesion count before treatment is discontinued. If the investigator 
determines all lesions are cleared at a visit, the investigator may instruct the subject to stop 
treatment. If treatment is stopped due to clearance, subjects will continue regularly scheduled 
visits through Week 12/ET and all procedures outside of study drug activities should be 
continued. If lesions recur or new lesions occur between visits after being stopped due to 
clearance, the subject or caregiver should re-initiate treatment to the recurring and new lesions. A 
new kit should be dispensed at Weeks 4 and 8 regardless of lesion count so that treatment can be 
restarted if lesions are observed between visits. An unscheduled visit is not required for the 
subject/caregiver to resume treatment. No study treatment is planned to be dispensed after the 
Week 12 visit.  
Remote visits may be performed at Week 4 using remote technology. During the Baseline visit, 
the subject/caregiver will be instructed on the technology to be used for remote visits. After the 


 
 
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initial molluscum lesion count is completed, it will be repeated by the same assessor and the 
subject/caregiver using the subject/caregiver’s electronic device that will be utilized to capture 
photographs for remote visits. This will provide the subject/caregiver an opportunity to practice 
with the technology and will allow for the assessor to understand lesion appearance in person 
compared to through the technology platform. 
Subjects will be contacted via phone on Day 2 to collect subject information on early dose 
reactions. At Weeks 16 and 20, subjects will be contacted via phone to capture information 
regarding MC recurrence and adverse events (AEs); at Week 24, the subject will be seen at the 
site for a final study visit to assess scarring, keloid, and MC recurrence.  
Subjects who discontinue the study prior to the Week 12 visit will be asked to complete the 
Week 12 visit assessments in the clinic: this will be recorded as an Early Termination (ET1) 
visit. Subjects who discontinue from the study after Week 12 but prior to Week 24 will be asked 
to come to the site to complete Week 24 assessments; this will be recorded as an ET2 visit. 
Safety assessments include BOTE Inflammation Scores, local skin reaction (LSR) scores, AE 
collection, including scarring/keloid, and urine pregnancy tests. Safety assessments will be 
completed at specified visits through Week 12. Adverse events and concomitant medications will 
be reviewed and updated as needed at each visit through Week 24. 
Inflammatory reactions around the MC lesions has been associated with imminent resolution of 
MC (sometimes referred to as “beginning-of-the-end” [“BOTE”] sign). The investigator (or 
designated evaluator) will assess the presence and overall degree of inflammatory reactions at 
MC lesions at Baseline (pre-dose) and Weeks 2 through 12 using the BOTE Inflammation Score 
in the table below. BOTE may be associated with itch, but not pain. BOTE is usually 
asymptomatic, self-limited, and localized to individual MC lesions and does not require 
discontinuation of study treatment or additional treatment. LSR is generally more diffuse, 
associated with significant itch or tenderness, may necessitate discontinuation of study treatment, 
and may need treatment for symptomatic relief (e.g., a topical corticosteroid or topical 
anesthetic). For very severe LSR, systemic corticosteroids may be considered. Investigators will 
assess the treatment area at each scheduled visit and use their medical judgement to differentiate 
between BOTE and LSR. BOTE Inflammation Score and LSR component scores will be 
recorded at each visit. BOTE should not be considered an AE. When LSRs are clinically 
significant at the application site, the investigator should report the condition as an AE(s). 
Prior to the first application of study drug at Baseline, the investigator will assess the subject’s 
skin as part of the physical examination, including the presence or absence of individual features 
of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. 
At Baseline (at least 30 minutes after dosing) and Week 2 through Week 12, the investigators 
will rate LSRs on individual features including erythema, flaking/scaling, crusting, swelling, 
vesiculation/pustulation, and erosion/ulceration using the LSR Assessment Scale.  


 
 
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The following tables describe the scoring parameters for the BOTE Inflammation Score and LSR 
score. 
BOTE Inflammation Score 
Score 
Global Assessment 
Description 
0 
No inflammation 
No evidence of local inflammation 
1 
Mild 
Minimal erythema and/or edema 
2 
Moderate 
Definite erythema and/or edema with or 
without hemorrhagic crusting 
3 
Severe 
Erythema and edema with definite 
hemorrhagic crusting 
4 
Very severe 
Strong reaction spreading beyond the 
treated area, bullous reaction, erosions 
 
LSR Score 
Score 
Erythema 
Flaking/ 
Scaling 
Crusting 
Swelling 
Vesiculation/ 
Pustulation 
Erosion/ 
Ulceration 
0 
Not present 
Not 
present 
Not 
present 
Not 
present 
Not present 
Not 
present 
1 
Slightly 
pink 
Mild, 
limited 
Isolated 
crusting 
Minimal, 
limited 
Fine vesicles 
Superficial 
erosion 
2 
Pink or 
light red 
Moderate 
Crusting   
< 50% 
Mild, 
palpable 
Scant 
transudate or 
exudate 
Moderate 
erosion 
3 
Red, 
restricted to 
treatment 
area 
Coarse 
Crusting   
> 50% 
Moderate 
Moderate 
transudate or 
exudate 
Marked, 
extensive 
4 
Red 
extending 
outside 
treatment 
area 
Scaling 
extending 
outside 
treatment 
area 
Crusting 
extending 
outside 
treatment 
area 
Marked 
swelling 
extending 
outside 
treatment 
area 
Marked 
transudate or 
exudate 
Black 
eschar or 
ulceration 
Adverse events will be assessed and collected after the initiation of study drug treatment through 
the end of the subject’s last visit. Treatment-related AEs and all serious adverse events will be 
followed up until resolution or up to one year after last treatment, whichever is sooner.  


 
 
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Scar formation (scars/keloids/hypertrophic scars) will be assessed starting at the Week 4 visit 
through Week 24. The investigator will map locations of the molluscum lesions at Baseline. 
Additional lesions identified through Week 12 will be added to the map. Using the map as a 
guidance, the investigator will assess the treated areas for scar/keloid formation. All scars, 
including keloid/hypertrophic scars, that develop after the Baseline assessment should be 
captured as AEs and assessed for relatedness to study treatment.  
If a subject’s treatment is discontinued by the investigator or the subject because of an AE, that 
AE should be indicated as the reason for treatment discontinuation. All subjects will be 
encouraged to remain in the study and to complete all required study visits throughout the 24-
week study duration. 
When approximately 200 subjects are randomized, a data safety monitoring board (DSMB) will 
review all available unblinded safety data (including completed patch testing results). The 
DSMB will provide their recommendation for the study to proceed or not proceed. 
5. DETERMINATION OF SAMPLE SIZE 
Approximately 850 subjects, 6 months of age and older, with a minimum of 3 and a maximum of 
70 MC lesions at Baseline will be randomized in a 1:1 (active:vehicle) scheme. The sample size 
assumptions for this study were informed by the integration of the completed phase 3 studies NI-
MC301 and NI-MC302. Multiple replications of simulated random sampling of the integrated 
NI-MC301 and NI-MC302 data was performed to ensure the sample size assumptions align with 
the proposed design of NI-MC304. This includes the 1:1 ratio (active:vehicle) and the 
percentages observed in NI-MC301 and NI-MC302 for each stratum of each of the stratification 
factors: investigator type, number of randomized subjects per household, and baseline BOTE 
score that are planned for NI-MC304. 
 
The analysis of the proportion of subjects with complete response of all treatable MC at Week 12 
within the Intent-to-Treat (ITT) Population of the multiple replications of simulated random 
sampled integrated data yields rates of 20% for vehicle and 29.5% for SB206 10.3% QD with the 
covariate-adjusted treatment difference was 9.5%. A sample size of 850 subjects (425 subjects in 
the SB206 10.3% QD group and 425 subjects in the vehicle group) will provide 90% power for a 
2-sided alpha test of size 0.05 to detect an absolute difference of 9.5% when the vehicle response 
rate is 20%.   
 
Simulations were performed with 10,000 replications to confirm the accuracy of these power 
estimates (i.e., true power and simulation based estimate of power) and to provide simulated 
median, 10% percentile and lowest detectable treatment difference estimates for a sample size of 
850 subjects. 
 
At the two-sided alpha=0.05 level, the median detectable treatment difference is approximately 
9.9% with a simulation based estimated power of 88%. The tenth percentile for detectable 
treatment difference is 7.1%, thus approximately 90% of the simulations with two-sided p < 0.05 


 
 
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produced an estimated treatment difference exceeding 7.1%. The lowest detectable treatment 
difference is 5.7%. 
 
At two-sided alpha levels <0.05, for example, p=0.025 level, the median detectable treatment 
difference is approximately 10.2% with a simulation based estimated power of 82%. The tenth 
percentile for detectable treatment difference is 7.7% and a lowest detectable difference of 6.5%. 
6. GENERAL ANALYSIS CONSIDERATIONS 
The statistical analyses will be reported using summary tables, listings, and figures (TLFs). The 
International Council for Harmonisation (ICH) numbering convention will be used for all TLFs. 
Unless otherwise noted, all statistical testing will be two-sided and will be performed at the 0.05 
significance level. Tests will be declared statistically significant if the calculated P-value is 
≤0.05.  
Continuous variable summaries will include the number of subjects (n) with non-missing values, 
mean, standard deviation (SD), median, minimum, and maximum. Other statistics such as 
quartiles, confidence intervals (CIs), and number of missing values may be added as appropriate.  
Categorical variable summaries will include the frequency and percentage of subjects who are in 
the category or each possible value. In general, the denominator for the percentage calculation 
will be based upon the total number of subjects in the study population within each treatment 
group, unless otherwise specified. The denominator for by-visit displays will be the number of 
subjects in the relevant study population with non-missing data at each visit.  
All summary tables will be presented by treatment group. Baseline summaries will also include 
an overall summary column.  
Individual subject data obtained from the eCRFs and any derived data will generally be 
presented by subject in data listings. Additionally, a listing of the subjects requiring a narrative 
because they experience one of the following events: serious adverse event, death, discontinued 
the study due to an AE, hypertrophic or keloid scarring, unresolved scars, or LSR suggestive of 
allergic contact dermatitis will be presented.  
A separate report for the results from the study exit interview will be created. 
The analyses described in this plan are considered a priori, in that they have been defined prior to 
breaking the blind.  
Any analyses performed subsequent to breaking the blind will be considered post hoc and 
exploratory. Post hoc analyses will be labeled as such on the output and identified in the clinical 
study report. 
All analyses and tabulations will be performed using SAS software Version 9.4 or higher. 
Tables, listings, and figures will be presented in RTF format.  


 
 
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The process for SAS program validation and quality control (QC) for programs and outputs is 
documented in the Synteract working instruction “SAS programming quality control.” 
Study-specific QC requirements can be found in Appendix B: SAS Programming QC 
Requirements. 
 
The study treatment period is defined from randomization through completion of Week 12/ET1 
visit and the safety follow-up period is from the completion of Week 12 through the completion 
of Week 24/ET2 visit. 
 
After all subjects have completed their Week 12/ET1 visit, thus completing the Treatment Period 
of the study, the database through Week 12/ET1 will be frozen and unblinded for purposes of the 
primary analysis of efficacy and safety. While this analysis is being prepared, the subjects will 
continue through Week 24/ET2. After all subjects have completed their Week 24/ET2 visit, the 
database will be locked and the follow-up data will be analyzed. 
7. NOTATION OF TREATMENT GROUPS AND VISITS 
Analysis visits 
 
Baseline is defined as the last non-missing value recorded prior to the first application of study 
drug. If time is not recorded and the assessment was on the same day as the first application of 
study drug, then it will be assumed the assessment occurred prior to the application of study drug. 
The baseline record will have an analysis visit of “Baseline”. If a subject was randomized but not 
treated, then baseline is defined as the last non-missing value on or before the date of 
randomization.  
 
For analysis of lesion counts, if there are multiple assessments of differing assessment types 
(remote vs in-clinic) within a given window, then the in-clinic lesion count will be used for 
analysis. For all evaluations of all parameters, assessments will be analyzed according to the visit 
at which they occurred (i.e., per the eCRF visit label). In order to account for the fact that the Week 
12 and Early Termination visits are collected on the same eCRF in the database, a check against 
the Study Exit form will be made to determine if the visit is a Week 12 or an Early Termination 
Visit. If the visit is an Early Termination visit, then the visit will be mapped according to the table 
below. If there is no corresponding Study Exit form on the same date, then it will be considered a 
Week 12 visit. If there is no assessment in a given visit, then the following visit windows will be 
applied to determine if an unscheduled visit may be used: 
 
Visit 
Analysis Visit 
Target Study 
Day 
Study Day Analysis 
Window 
Week 2 (±3 days) 
Week 2 
15 
Day 12 to 22 
Week 4 (±5 days) 
Week 4 
29 
Day 23 to 43 
Week 8 (±5 days) 
Week 8 
57 
Day 44 to 71 
Week 12 (±5 days) 
Week 12 
85 
Day 72 to 98 
Week 16 (±7 days) 
Week 16 
113 
Day 99 to 126 


 
 
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Visit 
Analysis Visit 
Target Study 
Day 
Study Day Analysis 
Window 
Week 20 (±7 days) 
Week 20 
141 
Day 127 to 154 
Week 24 (±7 days) 
Week 24 
169 
Day 155 to 182 
Days are measured from the date of randomization. Study days corresponding to measurements 
are calculated as: 
• Assessment date – date of randomization + 1, if assessment date is on or after the date of 
randomization. 
• Assessment date – date of randomization, if measurement date is before the date of 
randomization. 
In the event of multiple unscheduled records falling in the same analysis window, the assessment 
which is closest to the target study day will be chosen for analysis.  
8. ANALYSIS POPULATIONS 
The following subject population will be used for disposition analyses:  
• The Enrolled Population will consist of all subjects who have a signed informed consent 
or assent. If a subject is randomly assigned to a treatment, then treatment assignment will 
be based on randomized treatment; otherwise, they will be deemed a screen failure and 
will only appear in the overall summary columns of output. 
The following subject population will be used for safety analyses:  
• The Safety Population will consist of all subjects who receive at least 1 application of 
study treatment. Treatment assignment will be based on the treatment actually received. 
If a subject receives any amount of SB206, then they will be summarized in the SB206 
10.3% QD arm.  
The following subject populations will be used for efficacy analyses:  
• The ITT Population will consist of all subjects who are randomized who have a signed 
informed consent or assent as applicable. Treatment assignment will be based on the 
randomized treatment.  
• The Per-Protocol (PP) Population will consist of all subjects in the ITT Population who 
had no significant protocol deviations that impacted the analyses of efficacy endpoints. 
Final determination of subject inclusion in the PP Population will be made prior to 
unblinding. Treatment assignment will be based on the randomized treatment. 


 
 
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9. STUDY POPULATION 
9.1 Subject Disposition 
Subject disposition information will be summarized for all subjects by treatment group. 
Summaries will include: the number of subjects screened, the number of screen failures, the 
number of subjects in each analysis population, the number of subjects where study treatment 
stopped, primary reason for study treatment stopped, the number of subjects completing 12 
weeks of the study (defined as having answered Yes to the question “Did the subject complete 
treatment through Week 12?” on the end of treatment eCRF page or an end of treatment reason 
of “Complete Clearance Confirmed by Investigator Prior to Week 12” and does not have a Study 
Exit date prior to the subject’s Week 12 visit date), the number of subjects completed the study, 
and the primary reason for discontinuation (including summaries for prior to Week 12 and 
overall). 
 
A summary of the number of subjects in each center and each population will be presented.  
9.2 Eligibility 
A listing of subjects not fulfilling any eligibility criteria will be created. 
9.3 Demographic and Baseline Characteristics 
Demographic variables include age, sex, ethnicity, and race. Age will be calculated in years 
relative to the informed consent date.  
Other baseline characteristics include lesion counts at baseline, site type (dermatologist vs other), 
number of sites and a breakdown of site type, number of randomly assigned subjects in 
household (1 subject vs 2 subjects), number of households and breakdown of household size, 
BOTE score at Baseline (no inflammation [BOTE=0] vs mild/moderate/severe/very severe 
inflammation [BOTE≥1]), and age at and time since onset of symptoms of current molluscum 
episode. Descriptive statistics will be presented for ages and other continuous variables. 
Frequency counts and percentages will be presented for sex, ethnicity, race, and other categorical 
variables. Demographic and baseline characteristics will be summarized for the Safety, ITT, and 
PP Populations.  
9.4 Extent of Exposure 
Study drug exposure will be summarized for each treatment using the total number of 
applications, the duration of treatment, and the number of subjects requiring a treatment 
interruption and modification. Duration of treatment is defined as the last application date minus 
the first application date plus 1. A subject will be deemed to have a treatment interruption if there 
is at least 1 dose not applied due to investigator’s instruction and to have a treatment 
modification if there is at least 1 dose which was modified due to investigator instruction. 


 
 
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Study drug compliance will be summarized and calculated as follows: 
Compliance [%] = (Actual applications applied)/(Planned applications) ×100, where 
• Actual applications applied = Planned applications – the number of applications not 
applied by the subject which were not investigator instructed. 
• Planned applications = Number of applications (days) planned up to the point of 
treatment discontinuation or date of Week 12 visit, whichever is later.  
This implies that if a subject discontinues treatment prior to Week 12 due to complete clearance, 
then the number of applications takes this information into account and the subject is not 
penalized for having complete clearance.  
Compliance will be further summarized into 2 groups:  
1. Subjects who did not have any interruptions or modifications using the same formula as 
above, and 
2. Subjects with modifications or interruptions. For these subjects, an adjusted compliance 
will be calculated in the following manner: the actual applications applied will be the 
same as above but the planned applications will exclude the number of doses which were 
not applied due to investigator’s instruction.  
Subjects who do not have any interruptions or modifications will have no doses not applied due 
to investigator’s instruction and no doses modified due to investigator’s instruction. 
9.5 Protocol Deviations 
Significant protocol deviations that could potentially affect the efficacy or safety conclusions of 
the study will be identified prior to database lock and unblinding of individual subject treatment 
information. Significant protocol deviations may include, but are not limited to: 
• Randomly assigned subjects who did not satisfy selected inclusion and exclusion criteria 
• Randomly assigned subjects who developed withdrawal criteria during the study but were 
not withdrawn 
• Subjects who were randomized incorrectly including subjects of the same household who 
are randomized to different treatments  
• Subjects who received the wrong treatment 
• Subjects where the subject/site staff were unproperly unblinded 
• Week 12 Lesion Count not performed 
• Subjects who received an excluded concomitant treatment. 
The decision on the criteria for whether a subject is excluded from the PP Population will be 
made during the data review meeting prior to unblinding and database lock. Reasons for 
exclusion of a subject from the analysis will be listed. 


 
 
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A listing of all protocol deviations including the deviation designation (major or minor and 
significant or not), category, and indication of whether the deviation led to an exclusion of a 
subject from the PP Population will be presented in a data listing. Additionally, a listing of 
missed visits due to COVID-19 will be presented.   
Major and significant protocol deviations will be summarized by deviation category and 
treatment group.  
9.6 Medical History 
Medical history verbatim terms in the eCRFs will be mapped to system organ classes and 
preferred terms using the Medical Dictionary for Regulatory Activities (MedDRA) Version 23.0 
or later. Subject incidence of unique medical history terms by MedDRA system organ class and 
preferred term will be presented. The summary will be ordered by descending order of incidence 
in the SB206 treatment group of system organ class and preferred term within each system organ 
class. 
9.7 Prior and Concomitant Medications 
Prior and concomitant medication verbatim terms in the eCRFs will be mapped to 
anatomical/therapeutic/chemical (ATC) class and preferred names using the WHODrug Global 
B3 (version March 2020 or later). Prior medications are those medications started prior to the 
first application of study drug. Concomitant medications are those medications started on or after 
the date of first application of study drug or medications started prior to initial application of 
study drug and continued during the study. A medication can be classified as both prior and 
concomitant. If it cannot be determined whether the medication was a prior (or concomitant) 
medication due to a partial start or stop date, then it will be counted as both prior and 
concomitant; see Appendix A for the imputation of missing dates algorithm. 
Prior and concomitant medications will be summarized for each treatment by WHODrug Global 
ATC class Level 3 and preferred name. These summaries will present the number and percentage 
of subjects using each medication. Subjects may have more than 1 medication per ATC class and 
preferred name. At each level of subject summarization, a subject is counted once if he/she 
reported 1 or more medications at that level. Each summary will be ordered by descending order 
of incidence in the SB206 treatment group of ATC class and preferred name within each ATC 
class. 
10. EFFICACY ANALYSES 
The primary efficacy analysis will be based on the ITT Population. Additional supportive 
efficacy analyses will be performed using the PP Population. 


 
 
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10.1 Efficacy Endpoints 
The primary efficacy endpoint is the proportion of subjects with complete clearance of all 
treatable MC at Week 12.  
The secondary efficacy endpoints are the following: 
1) Proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at Week 12.  
2) Proportion of subjects achieving at least a 90% reduction from Baseline in the number of 
all treatable MC at Week 12. 
3) Proportion of subjects with complete clearance of all treatable MC at Week 8. 
4) Percent change from Baseline in the number of all treatable MC at Week 4. 
Complete clearance is defined as having a total number of lesions count of 0.  
The exploratory endpoints are the following: 
• Percent change from Baseline in number of treatable MC at each visit (Weeks 2, 8, 12) 
• Proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at Weeks 2, 
4, and 8 
• Proportion of subjects achieving at least a 90% reduction from Baseline in the number of 
all treatable MC at Weeks 2, 4, and 8 
• Proportion of subjects achieving at least a 75% reduction from Baseline in the number of 
all treatable MC at Weeks 2, 4, 8, and 12 
• Absolute change from Baseline in number of treatable MC at Weeks 2, 4, 8, 12 
• Proportion of subjects with complete clearance of all treatable MC at Week 2 and Week 4 
visits 
• Time to complete clearance of all treatable MC, defined as the days between the date of 
first dose and the first date of clearance. Subjects who do not achieve complete clearance 
will be censored at the date of the last lesion count assessment.  
• Proportion of subjects who have a recurrence of MC after the first visit at which complete 
clearance was observed, defined as the total lesion count being greater than 0 at any point 
after achieving a count of 0 
• Subject-reported spread to household members as measured by any new occurrence of 
MC in household members of subjects at each visit (Weeks 2, 4, 8, 12) 
• Investigator Global Severity Assessment at Baseline, Week 12, and Week 24 
• Subject Global Severity Assessment at Baseline, Week 12, and Week 24 
• Investigator Global Impression of Change at Week 12 and Week 24 


 
 
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• Subject Global Impression of Change at Week 12 and Week 24 
10.2 Baseline Values 
Unless otherwise noted, baseline is defined as the last non-missing value recorded prior to the 
first application of study drug. If time is not recorded and the assessment was on the same day as 
the first application of study drug, then it will be assumed the assessment occurred prior to the 
application of study drug. If a subject was randomized but not treated, then baseline is defined as 
the last non-missing value on or before the date of randomization. For lesion counts, the in-clinic 
count will be used as baseline and sensitivity analyses on type of assessment may be performed. 
10.3 Adjustments for Covariates 
The model for the primary efficacy will include adjustments for the following covariates: 
investigator type (dermatologist vs other), household number of randomized subjects (1 subject 
per household vs 2 subjects per household), BOTE score at Baseline (no inflammation 
[BOTE=0] vs mild/moderate/severe/very severe inflammation [BOTE≥1]), age (0 to <3, 3 to <4, 
4 to <5, 5 to <6, 6 to <7, 8 to <9, 9 to <12, and ≥12 years old), and baseline lesion count. If there 
are not at least 3 responders and non-responders at each level of the stratification factors, then 
that stratification factor will be removed from the model. If there are fewer than 10 
responders/non-responders, then neither investigator type nor household number of randomized 
subjects nor BOTE score at Baseline will be included in the model.  
10.4 Handling of Dropouts or Missing Data 
In analyses based on response, a missing response will be considered a non-responder.  
For a sensitivity analysis, subjects with missing lesion count at Week 12 but who demonstrated 
complete clearance at the last collected lesion assessment will be counted as responders.  
An additional sensitivity analysis using multiple imputation will be performed to address 
subjects with missing lesion count at Week 12. A monotone imputation model will be utilized in 
the following steps: 
1. The lesion count data will be imputed to follow a monotone missing data pattern using 
the Markov chain Monte Carlo method for 10 imputations. 
2. Each of the 10 imputations will then be imputed a further 10 times using a monotone 
regression method to impute the remaining missing data and the Week 12 lesion count 
using lesion count assessments at Weeks 2, 4, and 8, treatment group, investigator type 
(dermatologist vs other), BOTE score at Baseline (no inflammation [BOTE=0] vs 
mild/moderate/severe/very severe inflammation [BOTE≥1]), age (0 to <3, 3 to <4, 4 to 
<5, 5 to <6, 6 to <7, 8 to <9, 9 to <12, and ≥12 years old), and baseline lesion count as 
covariates. 


 
 
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3. Complete Clearance at Week 12 will be re-derived based on the imputed values and then 
analyzed using the primary analysis model. The results of the 100 analyses will be 
transformed into a normal statistic and combined into a single analysis using PROC 
MIANALYZE. 
The ROUND and MINIMUM options will be utilized in Steps 1 and 2 to ensure imputed values 
are non-negative integers. The seed to be used is 20200727. 
For subjects with a missing lesion count at Week 12 and identified as “Lost to Follow-up” by the 
investigator, the following sensitivity analysis will be performed. These lost to follow-up 
subjects will be contacted to obtain a patient reported outcome of MC disease status at the end of 
their study participation of either ‘Resolved (no lesions left)’, ‘Resolving (number of lesions 
decreasing)’, ‘Unchanged (number of lesions similar to previous clinic visit’, or ‘Worsening 
(number of lesions increased)’. A reported response endpoint will be derived in the following 
manner: 
• If a subject has a Week 12 lesion count assessment, then the subject will be deemed a 
responder if the count was 0. 
• If the subject did not have a Week 12 lesion count assessment and the response to the 
disease status was ‘Resolved (no lesions left)’ or ‘Resolving (number of lesions 
decreasing)’, then the subject will be deemed a responder. 
• Otherwise, the subject will be deemed a non-responder. 
The sensitivity analysis of this patient reported response will be analyzed in the same manner as 
the primary endpoint. A list of the patient reported outcome of MC disease status will be 
provided. 
A sensitivity analysis on the manner of assessment of lesion counts at Week 12 (in-clinic vs. 
remote) may be performed where subjects with only a remote assessment will be counted as 
non-responders. 
10.5 Interim Analysis and Data Monitoring 
When approximately 200 subjects are randomized, a DSMB will review all available unblinded 
safety data (including patch testing). All responsibilities of the DSMB and details of the analysis 
and data to be reviewed is detailed in the DSMB charter. 
10.6 Examination of Subgroups 
Subgroup analyses of complete clearance at Week 12 for investigator type (dermatologist vs 
other), household number of randomized subjects (1 subject per household vs 2 subjects per 
household), and BOTE score at Baseline (no inflammation [BOTE=0] vs 
mild/moderate/severe/very severe inflammation [BOTE≥1]) will be presented in a forest plot for 
the ITT Population. An additional subgroup analysis of complete clearance at Week 12 for age 


 
 
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(<1 year old, ≥1 to <2 years old, ≥2 to <6 years old, ≥6 to <12 years old, ≥12 to <18 years old, 
≥18 years old) and onset of MC symptoms duration prior to baseline (≤6 months vs >6 months) 
will be summarized descriptively for the ITT Population. 
10.7 Multiple Comparison/Multiplicity 
The familywise error rate with respect to the primary endpoint and secondary endpoints will be 
strongly controlled at the alpha=0.05 level using a hierarchical fixed sequence method testing 
strategy in the order listed in Section 10.1. If the primary endpoint is not statistically significant 
at the alpha=0.05 level, the secondary efficacy endpoints will be considered not significant. If the 
primary endpoint is statistically significant at the alpha=0.05 level, then the secondary efficacy 
endpoints will be tested in the following hierarchical fixed sequence:  
1) Proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at Week 12.  
2) Proportion of subjects achieving at least a 90% reduction from Baseline in the number of 
all treatable MC at Week 12. 
3) Proportion of subjects with complete clearance of all treatable MC at Week 8. 
4) Percent change from Baseline in the number of all treatable MC at Week 4. 
 
At each subsequent test of the secondary efficacy endpoints, if the secondary efficacy endpoint is 
not statistically significant at the alpha=0.05 level, the remaining secondary efficacy endpoints 
will be considered not statistically significant. If the secondary endpoint is statistically 
significant at the alpha=0.05 level, then the next subsequent secondary efficacy endpoint will be 
tested following the sequence.  
10.8 Multicenter Studies 
This is a multicenter study, having approximately 55 centers participating in the study. The 
center effects will be investigated in the primary statistical analysis model by including the 
treatment by investigator type interaction. As exploratory analyses to examine the variability of 
the treatment effect across centers, the following analyses will be performed: 
• Pool the centers into self-standing center pools of at least 18 subjects. The pooling will 
sort by investigator type and number of randomized subjects. Then, the centers with 
fewer than 18 subjects will be pooled until the self-standing center pool is at least 18 
subjects. The treatment effect will be explored using a logistic model including treatment, 
household number of randomly assigned subjects, age, baseline lesion counts, BOTE 
score at Baseline, and a strata statement which will include the pooling identified and 
examining the residual score statistics. To address treatment by center interaction, each 
pooling center will have a corresponding variable coded as 1 if on SB206 and 0 
otherwise. Some pooled centers may have a p-value of less than 0.05 by chance since 
there will be multiple pooled centers. 


 
 
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• Pool the centers using the method above but the self-standing center pools will contain at 
least 12 subjects. This analysis should be interpreted with caution due to the small sample 
size within pooled centers. 
11. METHODS OF EFFICACY ANALYSIS 
11.1 Primary Efficacy Analysis 
The primary efficacy comparison will test the following hypotheses: 
H0: The proportion of subjects with complete clearance is equal between SB206 10.3% QD 
and Vehicle; 
H1: The proportion of subjects with complete clearance is different between SB206 10.3% 
QD and Vehicle.  
 
The primary efficacy model will be the following for 𝜋𝜋𝐻𝐻𝑖𝑖 as the probability of complete 
clearance for the ith subject in household H: 
 
𝜋𝜋𝐻𝐻𝑖𝑖
= 𝑒𝑒ቀ𝛽𝛽0+𝛽𝛽1∗𝑋𝑋𝐻𝐻𝑖𝑖1+𝛽𝛽2∗𝑋𝑋𝐻𝐻𝑖𝑖2+𝛽𝛽3∗𝑋𝑋𝐻𝐻𝑖𝑖3+𝛽𝛽4∗𝑋𝑋𝐻𝐻𝑖𝑖4+𝛽𝛽5∗𝑋𝑋𝐻𝐻𝑖𝑖5+𝛽𝛽6∗𝑋𝑋𝐻𝐻𝑖𝑖6+𝛽𝛽7∗𝑋𝑋𝐻𝐻𝑖𝑖7+𝛽𝛽8∗𝑋𝑋𝐻𝐻𝑖𝑖8 +𝛽𝛽9∗𝑋𝑋𝐻𝐻𝑖𝑖9+𝛽𝛽10∗𝑋𝑋𝐻𝐻𝑖𝑖10+𝛽𝛽11∗𝑋𝑋𝐻𝐻𝑖𝑖11+𝛽𝛽12∗𝑋𝑋𝐻𝐻𝑖𝑖12+𝛽𝛽13∗𝑋𝑋𝐻𝐻𝑖𝑖13 ቁ
÷ [1
+ 𝑒𝑒ቀ𝛽𝛽0+𝛽𝛽1∗𝑋𝑋𝐻𝐻𝑖𝑖1 + 𝛽𝛽2∗𝑋𝑋𝐻𝐻𝑖𝑖2+ 𝛽𝛽3∗𝑋𝑋𝐻𝐻𝑖𝑖3+ 𝛽𝛽4∗𝑋𝑋𝐻𝐻𝑖𝑖4+ 𝛽𝛽5∗𝑋𝑋𝐻𝐻𝑖𝑖5 + 𝛽𝛽6∗𝑋𝑋𝐻𝐻𝑖𝑖6+ 𝛽𝛽7∗𝑋𝑋𝐻𝐻𝑖𝑖7+𝛽𝛽8∗𝑋𝑋𝐻𝐻𝑖𝑖8 +𝛽𝛽9∗𝑋𝑋𝐻𝐻𝑖𝑖9+𝛽𝛽10∗𝑋𝑋𝐻𝐻𝑖𝑖10+𝛽𝛽11∗𝑋𝑋𝐻𝐻𝑖𝑖11+𝛽𝛽12∗𝑋𝑋𝐻𝐻𝑖𝑖12+𝛽𝛽13∗𝑋𝑋𝐻𝐻𝑖𝑖13ቁ] 
 
where H = Household, i = subject within the household, 𝛽𝛽0 is the intercept,  
𝑋𝑋𝐻𝐻𝑖𝑖1 = ൜1, 𝑖𝑖𝑖𝑖 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝑖𝑖𝑖𝑖 𝑆𝑆𝑆𝑆206  
0, 𝑖𝑖𝑖𝑖 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝑖𝑖𝑖𝑖 𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 
 
𝑋𝑋𝐻𝐻𝑖𝑖2 = ൜1, 𝑖𝑖𝑖𝑖 𝑠𝑠𝑢𝑢𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑖𝑖𝑖𝑖 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑎𝑎 2 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 ℎ𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜ℎ𝑜𝑜𝑜𝑜𝑜𝑜
0, 𝑖𝑖𝑖𝑖 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑖𝑖𝑖𝑖 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑎𝑎 1 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 ℎ𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜ℎ𝑜𝑜𝑜𝑜𝑜𝑜 
 
𝑋𝑋𝐻𝐻𝑖𝑖3 = ൜1, 𝑖𝑖𝑖𝑖 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑖𝑖𝑖𝑖 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑎𝑎 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠
0, 𝑖𝑖𝑖𝑖 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑖𝑖𝑖𝑖 𝑓𝑓𝑟𝑟𝑟𝑟𝑟𝑟 𝑎𝑎𝑎𝑎 𝑂𝑂𝑂𝑂ℎ𝑒𝑒𝑒𝑒 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠              
 
𝑋𝑋𝐻𝐻𝑖𝑖4 = ൜1, if subject has a Baseline BOTE Score of 0    
0, if subject has a Baseline BOTE Score of ≥1  
 
𝑋𝑋𝐻𝐻𝑖𝑖6 = ൜1, if subject has a baseline age 0 to <3    
0, otherwise 
 
 
𝑋𝑋𝐻𝐻𝑖𝑖7 = ൜1, if subject has a baseline age 3 to <4    
0, otherwise 
 
 
𝑋𝑋𝐻𝐻𝑖𝑖8 = ൜1, if subject has a baseline age 4 to <5    
0, otherwise 
 


 
 
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𝑋𝑋𝐻𝐻𝑖𝑖9 = ൜1, if subject has a baseline age 5 to <6    
0, otherwise 
 
 
𝑋𝑋𝐻𝐻𝑖𝑖10 = ൜1, if subject has a baseline age 6 to <7    
0, otherwise 
 
𝑋𝑋𝐻𝐻𝑖𝑖11 = ൜1, if subject has a baseline age 7 to <8    
0, otherwise 
 
 
𝑋𝑋𝐻𝐻𝑖𝑖12 = ൜1, if subject has a baseline age 8 to <9    
0, otherwise 
 
 
𝑋𝑋𝐻𝐻𝑖𝑖13 = ൜1, if subject has a baseline age 9 to <12    
0, otherwise 
 
𝑋𝑋𝐻𝐻𝑖𝑖5is the subject’s baseline lesion count; treatment will be included in the class statement with 
PARAM=REF and REF=Vehicle. The working correlation will have an exchangeable structure. 
In the event of issues with convergence, an independent structure will be utilized. The model will 
include a repeated statement for subject household with household ID in the class statement. 
Also, the data structure will be ordered according to household ID and subject ID in household. 
 
Treatment groups will be compared using a generalized estimating equation for logistic 
regression with an exchangeable working correlation structure. The model will include 
treatment, investigator type (dermatologist vs other), household number of randomly assigned 
subjects (1 subject per household vs 2 subjects per household), BOTE score at Baseline (no 
inflammation [BOTE=0] vs mild/moderate/severe/very severe inflammation [BOTE≥1]), age (0 
to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, 8 to <9, 9 to <12, and ≥12 years old), and baseline lesion 
count as factors. For subjects from a household with 2 subjects, the actual values of BOTE score 
at Baseline and investigator type will be utilized with the recognition that such subjects did not 
have further stratification according to investigator type and BOTE score at Baseline. The odds 
ratio between SB206 10.3% and vehicle gel, 95% confidence intervals for the odds ratio, and P-
value for the covariate-adjusted treatment comparison will be presented together with predicted 
proportions along with their associated 95% confidence interval. The difference in proportion 
confidence interval will be calculated using the following formula: 
 
(𝑝𝑝𝑆𝑆𝑆𝑆206 − 𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖) ± 𝑧𝑧0.025
∗∗ 𝑆𝑆𝑆𝑆 
 
Where the SE = 
ඩ
𝑝𝑝𝑆𝑆𝑆𝑆206
2
(1 −𝑝𝑝𝑆𝑆𝑆𝑆206)2 𝑠𝑠𝑆𝑆𝑆𝑆206
2
+ 𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖
2
(1 −𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖)2 𝑠𝑠𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖
2
−2𝑝𝑝𝑆𝑆𝑆𝑆206(1 −𝑝𝑝𝑆𝑆𝑆𝑆206)𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 
(1 −𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖) ∗ቆ𝑠𝑠𝑆𝑆𝑆𝑆206
2
+ 𝑠𝑠𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖
2
− 𝑠𝑠𝑂𝑂𝑂𝑂𝑂𝑂𝑂𝑂 𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅
2
2
ቇ
 
The 𝑝𝑝𝑆𝑆𝑆𝑆206 and 𝑝𝑝𝑉𝑉𝑉𝑉ℎ𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 are the transformed predicted log odds at the mean of the covariates, s2’s 
are the standard errors of the predicted log odds and the odds ratio.  


 
 
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As a sensitivity analysis, the above primary analysis model will be applied to the PP Population. 
An additional sensitivity analysis counting subjects who discontinued prior to Week 12 or have a 
missing lesion count assessment but who demonstrated complete clearance at the last collected 
lesion assessment as responders will be presented. The impact of mis-stratifications may be 
explored via a sensitivity analysis.   
An analysis where the complete clearance response probability for each dropout prior to Week 
12 will be independently generated across the following scenarios (Vehicle response probability, 
SB206 response probability): 
 
(0.1, 0.1) 
(0.1, 0.0) 
 
 
 
(0.2, 0.2) 
(0.2, 0.1) 
(0.2, 0.0) 
 
 
(0.3, 0.3) 
(0.3, 0.2) 
(0.3, 0.1) 
(0.3, 0.0) 
 
(0.4, 0.4) 
(0.4, 0.3) 
(0.4, 0.2) 
(0.4, 0.1) 
(0.4, 0.0) 
 
The analysis will be produced 100 times and then the results for the estimated log odds ratio for 
treatment and its estimated standard error from each of the imputations will be combined using 
PROC MIANALYZE. 
An additional sensitivity analysis will be performed in a subset of the ITT population where only 
1 subject from each household is chosen to contribute to the model based on the subject with the 
highest number of baseline treatable MC and the oldest to break ties, if needed. A logistic 
regression model including treatment, investigator type, BOTE score at Baseline. age, and 
baseline lesion counts will be utilized. 
11.2 Secondary Efficacy Analyses 
The secondary endpoints of the proportion of subjects achieving a lesion count of 0 or 1 of all 
treatable MC at Week 12, proportion of subjects achieving at least a 90% reduction from 
Baseline in the number of all treatable MC at Week 12, and the proportion of subjects with 
complete clearance of all treatable MC at Week 8 will be analyzed in the same manner as the 
primary endpoint.  
Since the within-household correlation is expected to be small, the percent change from Baseline 
in the number of all treatable MC at Week 4 will be analyzed using a repeated measures mixed 
model for the respective visits with the same covariates as the primary model together with visits 
and treatment by visit interaction; an unstructured covariance matrix will be utilized. If the 
calculation of the percent change from baseline is influenced by outliers with calculated values 
>100%, then the influence of outliers will be avoided for analysis by censoring them so that all 
values were in the range of -100% to 100%. If the model fails to converge, then other correlation 
structures will be explored. 


 
 
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A sensitivity analysis using the PP Population will be provided for the proportion of subjects 
achieving a lesion count of 0 or 1 of all treatable MC at Week 12 and the proportion of subjects 
achieving at least a 90% reduction from Baseline in the number of all treatable MC at Week 12.  
11.3 Exploratory Analyses 
Since the within-household correlation is expected to be small, the change and percent change 
from Baseline in the number of treatable MC at Weeks 2, 8 and 12 will be analyzed using a 
repeated measures mixed model for the respective visits with the same covariates as the primary 
model together with visits and treatment by visit; an unstructured covariance matrix will be 
utilized. If the calculation of the percent change from baseline is influenced by outliers with 
calculated values >100%, then the influence of outliers will be avoided for analysis by censoring 
them so that all values were in the range of -100% to 100%. If the model fails to converge, then 
other correlation structures will be explored. 
The exploratory endpoints based on the proportion of subjects achieving complete clearance (at 
Weeks 2 and 4) or 75% (at Weeks 2, 4, 8, and 12) or 90% (at Weeks 2, 4, and 8) reductions will 
be analyzed in the same manner as the primary endpoint.  
Likewise, the proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at 
Weeks 2, 4 and 8 will be analyzed in the same manner as the primary endpoint. 
Since the within-household correlation is expected to be small and time to first complete 
clearance of all MC is exploratory, it will be analyzed using Kaplan-Meier methods. The number 
and percentage of subjects achieving complete clearance, number and percentage of censored 
subjects, and Kaplan-Meier estimates of first quartile, median, and third quartile will be 
summarized by treatment group. Differences in Kaplan-Meier curves between the treatments will 
be tested for significance using a stratified log-rank test. 
The proportion of subjects who have a recurrence of MC after the first visit at which complete 
clearance was observed will be summarized. 
The subject-reported spread of MC to household members not in the study will be summarized 
descriptively including a breakdown of whether or not there was any spread and then a 
breakdown of the amount of spread within the household at each visit at the household level.  
A shift table comparing the baseline global severity assessment to each scheduled postbaseline 
assessment will be presented by subject and investigator. The Investigator and Subject Global 
Impression of change will be summarized descriptively. 
Separate plots of the cumulative distribution function of the percentage change from Baseline in 
lesion count at Week 12 across each of the scores for the Subject Global Impression of Change 
and the Subject Global Severity Assessment will be presented for all subjects. These plots will 
also be replicated separately for subjects in the SB206 10.3% QD group and for subjects in the 
Vehicle group. 


 
 
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A plot comparing Improved vs Not Improved, including the correlation between percentage 
change from Baseline in lesion count at Week 12 and improvement category, in each treatment 
group and overall will be presented separately for the Subject Global Impression of Change at 
Week 12. Improved will be defined as selecting either ‘Very Much Improved’, ‘Much 
Improved’, or ‘Minimally Improved’ and not improved as selecting either ‘No Change’, 
‘Minimally Worse’, ‘Much Worse’, or ‘Very Much Worse’.  
A plot comparing No Severity vs Severity, including the correlation between percentage change 
from Baseline in lesion count at Week 12 and severity category, in each treatment group and 
overall will be presented separately for the Subject Global Severity Assessment at Week 12. No 
Severity will be defined as having a response of ‘None’ and Severity will be defined as having a 
response of ‘Mild’, ‘Moderate’, ‘Severe’, or ‘Very Severe’.  
The correlation between the following will be presented. 
• Baseline lesion count and Subject Global Severity Assessment at Baseline 
• Baseline lesion count and Subject Global Severity Assessment at Week 12 
• Baseline lesion count and Subject Global Impression of Change at Week 12 
• Baseline lesion count and Investigator Global Severity Assessment at Baseline 
• Baseline lesion count and Investigator Global Severity Assessment at Week 12 
• Baseline lesion count and Investigator Global Impression of Change at Week 12 
The following efficacy endpoints will be descriptively summarized for the Improved vs Not 
Improved categories of the Subject Global Impression of Change at Week 12. 
• Proportion of subjects with complete clearance of all treatable MC at Week 12. 
• Proportion of subjects achieving a lesion count of 0 or 1 of all treatable MC at Week 12. 
• Proportion of subjects achieving at least a 90% reduction from Baseline in the number of 
all treatable MC at Week 12. 
• Proportion of subjects achieving at least a 75% reduction from Baseline in the number of 
all treatable MC at Week 12. 
• Percent change from Baseline in the number of treatable MC at Week 12. 
12. OTHER ANALYSES 
The following analyses of BOTE vs lesion count will be presented: 
• Percent change from Baseline in the number of treatable MC at each visit in relation to 
the Baseline BOTE score comparing No Inflammation vs Inflammation within each 
treatment group through a repeated measures mixed model with number of randomly 
assigned subjects in household (1 subject vs 2 subjects), investigator type (dermatologist 


 
 
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vs other), BOTE score at Baseline (no inflammation [BOTE=0] vs 
mild/moderate/severe/very severe inflammation [BOTE≥1]), BOTE score at Baseline by 
visit interaction, age, and baseline lesion count as covariates with a compound symmetry 
covariance matrix. 
• Percent change from Baseline in the number of treatable MC at Week 12 in relation to the 
highest post-baseline BOTE score during treatment will be summarized descriptively. 
• Percent change from Baseline in the number of treatable MC at Week 12 in relation to the 
highest BOTE score at any visit (including Baseline) will be summarized descriptively. 
• Percent change from Baseline in the number of treatable MC at each visit in relation to 
the BOTE score at Week 2 will be summarized descriptively. 
In these analyses, the BOTE scores will be analyzed in the ITT Population as follows: 
1. Dichotomized: 
a. Score of 0: No Inflammation 
b. Score of 1, 2, 3, or 4: Mild to Very Severe 
A shift table comparing the baseline BOTE score to each scheduled post-baseline assessment 
will be presented for the ITT Population.  
13. SAFETY ANALYSES 
All safety analyses will be based on the Safety Population. 
 
A listing of all deaths will be presented. 
13.1 Adverse Events 
Adverse event summaries restricted to treatment-emergent AEs (TEAEs) will include those AEs 
that occurred any time on or after the first in-clinical application of study drug through the last 
application of study drug and those existing AEs that worsened during this same period. If it 
cannot be determined whether the AE is treatment emergent due to a partial onset date, then it 
will be counted as such; see Appendix A for the imputation of missing dates algorithm. Post 
treatment AEs will include those AEs that occurred after the last application of study drug. 
Verbatim terms in the eCRFs will be mapped to preferred terms and system organ classes using 
the MedDRA Version 23.0 or later.  
Each AE summary will be displayed by treatment group. Summaries that are displayed by 
system organ classes and preferred terms will be ordered by descending order of incidence in 
SB206 treatment group of system organ class and preferred term within each system organ class. 
Summaries of the following types will be presented: 
• Overall summary of TEAEs and post treatment AEs that contain an overview of each 
item below. 


 
 
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• Subject incidence of TEAEs with total number of unique TEAEs and post treatment AEs 
with total number of unique post treatment AEs by MedDRA system organ class and 
preferred term.  
• Subject incidence of TEAEs and post treatment AEs by MedDRA system organ class, 
preferred term, and maximum severity. At each level of subject summarization, a subject 
is classified according to the maximum severity if the subject reported 1 or more events. 
Adverse events with missing severity will be considered severe for this summary. 
• Subject incidence of TEAEs by MedDRA system organ class, preferred term, and closest 
relationship to study drug (Related/Not Related). Related AEs are those reported as 
“Definite,” “Probable,” or “Possible,” and unrelated AEs are those reported as “Unlikely” 
or “Unrelated.” At each level of subject summarization, a subject is classified according 
to the closest relationship if the subject reported 1 or more events. Adverse events with a 
missing relationship will be considered related for this summary. 
• Subject incidence of serious TEAEs with total number of unique serious TEAEs and post 
treatment serious AEs with total number of unique post treatment serious AEs by 
MedDRA system organ class and preferred term.  
• Subject incidence of TEAEs leading to study drug discontinuation by MedDRA system 
organ class and preferred term. 
• Subject incidence of TEAEs leading to study discontinuation and post treatment AEs 
leading to study discontinuation by MedDRA system organ class and preferred term. 
• Subject incidence of TEAEs leading to death as an outcome by MedDRA system organ 
class and preferred term. 
• Subject incidence of Transient TEAEs, identified based on a search of verbatim terms 
containing ‘TRANSIENT’. 
Separate listings of all AEs, all SAEs, all TEAEs leading to study drug discontinuation, all AEs 
leading to study discontinuation, ongoing treatment related AEs, and all post treatment AEs will 
be provided.  
The proportion of subjects with scarring and the proportion of subjects with keloid or 
hypertrophic scarring will be summarized descriptively at each visit. 
13.2 Local Skin Reaction 
The LSR composite score will be calculated by summing up all the numerical responses (0-4) to 
each individual parameter for a composite score that ranges between 0 and 24. The observed and 
change from Baseline values of the LSR composite score will be summarized descriptively at 
each visit. This analysis will be repeated based on the dichotomized baseline BOTE score 
described in Section 12. 


 
 
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A table summarizing each LSR parameter (erythema, flaking/scaling, crusting, swelling, 
vesiculation/pustulation, and erosion/ulceration) score at each scheduled post-baseline 
assessment will be presented. This analysis will be repeated based on the dichotomized baseline 
BOTE score described in Section 12. 
Additionally, a shift table comparing the baseline score for each LSR parameter to each 
scheduled postbaseline assessment will be presented for the Safety Population. 
13.3 Events of Special Interest 
Events of Special Interest will include subjects with any TEAE where the preferred term contains 
“application site”, subjects with at least 1 post-baseline occurrence of moderate BOTE 
inflammation score, or subjects with at least 1 post-baseline LSR component score ≥1. A 
summary including the number and percentage of subjects with at least 1 event of special 
interest, AEs of interest by MedDRA system organ class and preferred term, at least 1 moderate 
BOTE inflammation score, and any LSR component score ≥1 will be provided for the Safety 
Population. The analysis will also be repeated with the LSR criteria revised to include any post-
baseline LSR component (excluding erythema) score ≥1 and erythema score ≥2. 
13.4 Urine Pregnancy Test 
Urine pregnancy test results will be included in a data listing only.  
13.5 Physical Examination 
A shift table summarizing the shift from Baseline to end of treatment in normal/abnormal will be 
presented.  
13.6 Patch Testing 
A table summarizing any patch testing results by time point may be presented.  
14. CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
There were no modifications and/or clarifications to the methodology specified in the protocol. 
 
 


 
 
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15. REFERENCES 
US Department of Health and Human Services (DHHS), Food and Drug Administration, Center 
for Drug Evaluation and Research (CDER). Guidance for industry ICH E9: Statistical principles 
for clinical trials. September 1998 [cited 2019 May 20]. Available from: 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm
073137.pdf


 
 
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APPENDICES 
Appendix A: Presentation of Data and Programming Specifications 
General  
• Specialized text styles, such as bold, italics, borders, and shading will not be used in 
tables, figures, and data listings unless they add significant value to the table, figure, or 
data listing. 
• Only standard keyboard characters are to be used in tables and data listings. 
• Special characters, such as nonprintable control characters, printer-specific, or font-
specific characters, will not be used on a table, figure, or data listing. 
• Hexadecimal character representations are allowed (e.g., µ, α, ß). 
• All footnotes will be left justified and at the bottom of a page. Footnotes must be used 
sparingly and must add value to the table, figure, or data listing. 
 
Tables 
• Formal organization of tabulations may be changed during programming, if appropriate, 
e.g., tables for the different variables may be combined into a single table, or tables with 
more than 1 variable may be split into several tables. 
• Means and medians will be presented to 1 more decimal place than the raw data. 
Standard deviations will be presented to 2 more decimal places than the raw data. 
Minimums and maximums will be reported with the same number of decimal places as 
the raw data.  
• Percentages will be presented to the tenths place. 
• For frequency counts of categorical variables, categories whose counts are zero will be 
displayed for the sake of completeness. For example, if none of the subjects discontinue 
due to “lost to follow-up,” this reason will be included in the table with a count of 0. 
Categories with zero counts will not have zero percentages displayed. 
• Lower and upper confidence interval values must be presented to 1 decimal place more 
than the raw/derived data (i.e., to the same number of decimal places as the mean). 
• Percentiles (e.g., 25%, 75%) must be presented to 1 decimal place more than the 
raw/derived data. 
• For all inferential analyses, P values will be rounded to 4 decimal places (or at the 
highest level of precision) with a leading zero (0.0001). P values less than 0.0001 will be 
presented as “<0.0001.” 
• The last footnotes will be 
- 
“Source: xxx”, where xxx indicates the source table number(s) if applicable (in case aggregated 
results like mean or median are plotted) or the source listing(s) (in case individual responses are 
plotted) and/or source dataset(s) (e.g., AdaM).  
- 
“PROGRAM SOURCE: …\\xx.sas, DATA CUT OFF DATE: DDMMMYYYY, RUN DATE: 
DDMMYY hh:mm”. 
where extract date (e.g., data cut off, database lock) is the date stamp of the data snapshot 
used. 


 
 
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Figures 
• Legends will be used for all figures with more than 1 variable or item displayed. 
Treatment group sizes (n=xx) will be included, as appropriate. 
• Figures will be in black and white but can be in color to add value to the clarity and 
readability of a figure. Lines must be wide enough to see the line after being copied. 
• For box plots, the horizontal line will represent the median, + represents the group mean, 
the length of the box represents the interquartile range (25th-75th percentiles), and the 
whiskers will represent the minimum and maximum. 
• The last footnotes will be 
- 
“Source: xxx”, where xxx indicates the source listing number(s) and/or source dataset(s) (e.g., AdaM).  
- 
“PROGRAM SOURCE: …\\xx.sas, DATA CUT OFF DATE: DDMMMYYYY, RUN DATE: 
DDMMYY hh:mm”. 
where extract date (e.g., data cut off, database lock) is the date stamp of the data snapshot 
used. 
 
Listings 
• Formal organization of the listing may be changed during programming, if appropriate, 
e.g., additional variables may be included, change in the column order, or the listing may 
be split into multiple parts due to space constraints. 
• If not otherwise specified, all data listings will be sorted by sequence/treatment, center, 
subject number, visit, and date/time, as appropriate.  
• All date values will be presented in a SAS date (e.g., 29AUG2001) format.  
• All observed time values will be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45 or 11:26). Seconds will only be reported if they were measured as part of 
the study. 
• The last footnote will be 
- 
“PROGRAM SOURCE: …\\xx.sas, DATA CUT OFF DATE: DDMMMYYYY, RUN DATE: 
DDMMYY hh:mm”. 
where extract date (e.g., data cut off, database lock) is the date stamp of the data snapshot 
used. 
 
 
 


 
 
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Missing or incomplete dates (i.e., AEs, concomitant medications, and start dates of current 
molluscum episode and initial diagnosis) 
The most conservative approach will be systematically considered. If the AE onset date is 
missing/incomplete, it is assumed to have occurred during the study treatment phase (i.e., 
considered a TEAE) except if the partial onset date or other data, such as the stop date, indicates 
differently. Similarly, a medication with partial start and stop dates could be considered as both a 
prior and concomitant treatment. 
 
The following algorithms will be applied to missing and incomplete start and stop dates: 
 
Start Dates 
• If the day portion of the start date is missing, then the start date will be estimated to be 
equal to the date of first application of study drug, provided the start month and year are 
the same as the first application of study drug and the stop date is either after the first 
application of study drug or completely missing. Otherwise, the missing day portion will 
be estimated as “01.” 
• If both the day and month portions of the start date are missing, then the start date will be 
estimated to be equal to the date of first application of study drug, provided the start year 
is the same as the first application of study drug and the stop date is either after the first 
application of study drug or completely missing. Otherwise, the event will be assumed to 
start on the first day of the given year (e.g., ??-???-2013 is estimated as 01-JAN-2013) or 
the subject’s date of birth, whichever is latest. 
• If the start date is completely missing and the stop date is either after the application of 
study drug or completely missing, the start date will be estimated to be the first day of 
study drug application. Otherwise, the start date will be estimated to be the first day of 
the same year as the stop date or the subject’s date of birth, whichever is latest. All other 
non-AE and non-concomitant medication day calculations where only partial dates are 
available will be handled as follows: the first day of the month will be used in the 
calculations if the day part of a start date is missing while January 1 will be employed if 
both the month and day parts of a start date are missing. 
 
Stop Dates 
• If only the day of resolution is unknown, the day will be assumed to be the last day of the 
month (e.g., ??-JAN-2013 will be treated as 31-JAN-2013).  
• If both the day and month of resolution are unknown, the event will be assumed to have 
ceased on the last day of the year (e.g., ??-???-2013 will be treated as 31-DEC-2013).  
• If the stop date is completely missing and the event is not continuing, the event will be 
assumed to be after first application of study drug and will be imputed using the last 
known date on the study. 
 
For the start dates of current molluscum episode and initial diagnosis, the day will be estimated 
as “01” if only day is missing. If both month and day are missing, then it will be estimated as 
“01-JUN-YYYY” or the subject’s date of birth, whichever is latest. 


 
 
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If the start date of current molluscum episode is partial, then the following imputation will be 
made: 
• If only the day is unknown, the day will be assumed to be the first day of the month or 
the date of birth, whichever is later. 
• If the day and month are missing, then the start date will be estimated to be June 1st or the 
date of birth, whichever is later. 
 
Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
• Days – A duration expressed in days between 1 date (date1) and another later date (date2) is 
calculated using the formulas noted below: 
Duration in days = date2 – date1 + 1. 
• Months – A duration expressed in months will be calculated as (later date – earlier date + 
1)/(30.4167). 
• Years – A duration expressed in years will be calculated as (later date – earlier date + 
1)/(365). 
• Change from Baseline – Change from Baseline will be calculated as follows: 
Change from Baseline = postbaseline value – baseline value. 
• Percent change from Baseline – Change from Baseline will be calculated as follows: 
Percent change from Baseline = (postbaseline value – baseline value)/baseline value  
× 100. 
 
 


 
 
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Appendix B: SAS Programming QC Requirements  
Derived datasets are independently programmed by two programmers. The separate datasets 
produced by the 2 programmers must match 100%. Detailed specifications for the derived 
datasets are documented in the study analysis dataset specifications provided to the client at 
study conclusion. 
Tables are independently reprogrammed by a second programmer for numeric results.  
Listings are checked for consistency against corresponding tables, figures, and derived datasets. 
Figures are checked for consistency against corresponding tables and listings, or independently 
reprogrammed if there are no corresponding tables or listings. 
The entire set of TLFs is checked for completeness and consistency prior to its delivery to the 
client by the lead biostatistician and a senior level, or above, reviewer.


 
 
 
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Appendix C:  List of Tables, Figures, and Listings 
The following proposal for section 14 and 16.2 is completed according to ICH E3 guidelines. The ICH heading numbers and description are in bold. 
Minor changes from this planned index do not need to be amended in the SAP.  
 
Formal organization of tabulations may be changed during programming, if appropriate, e.g., tables for the different variables may be combined into 
a single table, or tables with more than 1 variable may be split into several tables. 
 
The shells for the outputs below are contained in the file titled “Novan NI-MC302 SAP TLFs Version 2.0”. 
  
TABLES, FIGURES, AND GRAPHS  
Table 
Number 
 
Table Title 
Analysis Population 
14 
TABLES, FIGURES, AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE 
TEXT 
 
14.1 
DEMOGRAPHIC DATA 
 
14.1.1.1 
Subject Disposition 
Enrolled 
14.1.1.2 
Enrollment by Site 
ITT 
14.1.2.1 
Demographic and Baseline Characteristics  
Safety 
14.1.2.2 
Demographic and Baseline Characteristics 
ITT 
14.1.2.3 
Demographic and Baseline Characteristics 
PP 
14.1.3.1 
Study Drug Exposure 
Safety 
14.1.3.2 
Study Drug Compliance 
Safety 
14.1.4 
Significant and Major Protocol Deviations 
ITT 
14.1.5 
Medical History 
ITT 
14.1.6.1 
Prior Medications 
ITT 
14.1.6.2 
Concomitant Medications 
ITT 
14.2 
Efficacy data 
 
14.2.1.1 
Complete Clearance Lesion Count Response at Week 12 
ITT 
14.2.1.2 
Complete Clearance Lesion Count Response at Week 12 
PP 


 
 
 
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Table 
Number 
 
Table Title 
Analysis Population 
14.2.1.3 
Sensitivity Analysis: Complete Clearance Lesion Count Response at Week 12 
ITT 
14.2.1.4 
Sensitivity Analysis: Complete Clearance Lesion Count Response at Week 12 
PP 
14.2.1.6 
Proportion of Subjects with Complete Clearance at Week 12 by Subgroup 
ITT 
14.2.1.7 
Dropout Sensitivity Analysis: Complete Clearance Lesion Count Response at Week 12 
ITT 
14.2.1.8 
One Subject Per Household Sensitivity Analysis: Complete Clearance Lesion Count Response 
at Week 12 
ITT 
14.2.1.9 
Exploratory Analysis of the Variability of Treatment Effect of Complete Clearance Lesion 
Count Response at Week 12 Across Pools of at Least 18 Subjects 
ITT 
14.2.1.10 
Exploratory Analysis of the Variability of Treatment Effect of Complete Clearance Lesion 
Count Response at Week 12 Across Pools of at Least 12 Subjects 
ITT 
14.2.1.11 
Multiple Imputation Sensitivity Analysis: Complete Clearance Lesion Count Response at Week 
12 
ITT 
14.2.1.12 
Patient Reported Response Sensitivity Analysis: Complete Clearance Lesion Count Response at 
Week 12 
ITT 
14.2.2.1.1 
Complete Clearance Lesion Count of 0 or 1 Response at Week 12 
ITT 
14.2.2.1.2 
Complete Clearance Lesion Count of 0 or 1 Response at Week 12 
PP 
14.2.2.2.1 
Summary of a 90% Reduction in Lesion Counts from Baseline Response at Week 12 
ITT 
14.2.2.2.2 
Summary of a 90% Reduction in Lesion Counts from Baseline Response at Week 12 
PP 
14.2.2.3 
Complete Clearance Lesion Count Response at Week 8 
ITT 
14.2.2.4.1 
Percent Change from Baseline in Lesion Counts by Visit 
ITT 
14.2.3.1 
Complete Clearance Lesion Count of 0 or 1 Response at Weeks 2, 4 and 8 
ITT 
14.2.3.2 
Summary of a 90% Reduction in Lesion Counts from Baseline at Weeks 2, 4 and 8 
ITT 
14.2.3.3 
Summary of a 75% Reduction in Lesion Counts from Baseline Response by Visit 
ITT 
14.2.3.4.1 
Change from Baseline in Lesion Count by Visit 
ITT 
14.2.3.5 
Complete Clearance Lesion Count Response at Weeks 2 and 4 
ITT 
14.2.3.6.1 
Kaplan-Meier Estimates of Time to Complete Clearance (Days) from Start of Dosing 
ITT 
14.2.3.7 
Summary of Recurrence after Complete Clearance 
ITT 
14.2.3.8 
Summary of Increase in Subject-Reported Spread to Household Members by Visit 
ITT 
14.2.3.9.1 
Summary of Global Severity Assessment by Assessor and Visit 
ITT 


 
 
 
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Table 
Number 
 
Table Title 
Analysis Population 
14.2.3.10.1 
Summary of Global Impression of Change by Assessor and Visit 
ITT 
14.2.3.10.4 
Summary of Efficacy by Subject Global Impression of Change Improvement at Week 12 
ITT 
14.2.3.11 
Analysis of Correlation of Lesion Count with Global Severity Assessment and Global 
Impression of Change 
ITT 
14.2.3.12.1 
Analysis of Lesion Counts by Dichotomized BOTE Score 
ITT 
14.2.3.12.2 
Summary of Lesion Counts by Highest Post-Baseline Dichotomized BOTE Score 
ITT 
14.2.3.12.3 
Summary of Lesion Counts by Highest Dichotomized BOTE Score 
ITT 
14.2.3.12.4 
Summary of Percent Change from Baseline in Lesion Count over Time by Dichotomized Week 
2 BOTE Score 
ITT 
14.2.3.12.5 
Summary of the Beginning of the End (BOTE) Inflammation Score Results by Visit 
ITT 
14.3 
Safety data 
 
14.3.1 
Displays of Adverse Events 
 
14.3.1.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
14.3.1.1.2 
Overall Summary of Post Treatment Adverse Events 
Safety 
14.3.1.2.1 
Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety 
14.3.1.2.2 
Summary of Post Treatment Adverse Events by System Organ Class and Preferred Term 
Safety 
14.3.1.3.1 
Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and 
Maximum Severity 
Safety 
14.3.1.3.2 
Summary of Post Treatment Adverse Events by System Organ Class, Preferred Term, and 
Maximum Severity 
Safety 
14.3.1.4 
Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and 
Relationship to Study Drug 
Safety 
14.3.1.5.1 
Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term 
Safety 
14.3.1.5.2 
Summary of Serious Post Treatment Adverse Events by System Organ Class and Preferred 
Term 
Safety 
14.3.1.6 
Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by 
System Organ Class and Preferred Term 
Safety 


 
 
 
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Table 
Number 
 
Table Title 
Analysis Population 
14.3.1.7 
Summary of Treatment-Emergent Adverse Events Leading to Death by System Organ Class and 
Preferred Term 
Safety 
14.3.1.8.1 
Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by System 
Organ Class and Preferred Term 
Safety 
14.3.1.8.2 
Summary of Post Treatment Adverse Events Leading to Study Discontinuation by System 
Organ Class and Preferred Term 
Safety 
14.3.1.9 
Summary of Transient Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term 
Safety 
14.3.2 
Listings of deaths, other serious and significant adverse events 
 
14.3.2.1 
Listing of Serious Adverse Events 
Safety 
14.3.2.2 
Listing of Adverse Events Leading to Study Drug Discontinuation 
Safety 
14.3.2.3 
Listing of Deaths 
Safety 
14.3.6 
Other safety data 
 
14.3.6.1.1 
Summary of Local Skin Reaction (LSR) Composite Score by Visit 
Safety 
14.3.6.1.2 
Summary of Local Skin Reaction (LSR) Score Results by Visit 
Safety 
14.3.6.1.3 
Shift Summary of Local Skin Reaction (LSR) Score Results by Visit 
Safety 
14.3.6.1.4 
Summary of Local Skin Reaction (LSR) Composite Score by Dichotomized Baseline BOTE 
Score and Visit 
Safety 
14.3.6.1.5 
Summary of Local Skin Reaction (LSR) Individual Score by Dichotomized Baseline BOTE Score 
and Visit 
Safety 
14.3.6.2 
Summary of Events of Special Interest 
Safety 
14.3.6.3 
Summary of Physical Examination Findings 
Safety 
14.3.6.4 
Summary of Scarring and Keloid by Visit 
Safety 
14.3.6.5 
Summary of Patch Testing Results 
Safety 
 
  


 
 
 
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                                                                                                 Statistical Analysis Plan 
NI-MC304 
                                                                                                                     24May2021 
 
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Figure 
Number 
 
Figure Title 
Analysis Population 
14.2.1.5 
Forest Plot: Odds Ratio (95% CI) of the Proportion of Subjects with Complete Clearance at 
Week 12 
ITT 
14.2.2.4.2 
Percent Change from Baseline in Lesion Count over Time by Treatment Group 
ITT 
14.2.3.4.2 
Mean Change from Baseline in Lesion Count over Time by Treatment Group 
ITT 
14.2.3.6.2 
Kaplan-Meier Plot of Time to Complete Clearance (Days) from Start of Dosing 
ITT 
14.2.3.9.2 
Cumulative Distribution Function Plot Across Subject Global Severity Assessment Responses 
ITT 
14.2.3.9.3 
Cumulative Distribution Function Plot by Subject Global Severity Assessment Severity 
Category 
ITT 
14.2.3.10.2 
Cumulative Distribution Function Plot Across Subject Global Impression of Change Responses 
ITT 
14.2.3.10.3 
Cumulative Distribution Function Plot by Subject Global Impression of Change Improvement 
Category 
ITT 
  
 


 
 
 
Novan, Inc.  
                                                                                                 Statistical Analysis Plan 
NI-MC304 
                                                                                                                     24May2021 
 
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Section 16.2: List of Data Listings 
 
ICH Listing 
Number 
 
Listing Title 
Analysis 
Population 
16.1.7 
Subject Randomization 
ITT 
16.2 
SUBJECT DATA LISTINGS 
 
16.2.1 
Discontinued subjects 
 
16.2.1.1 
Subject disposition 
Enrolled 
16.2.2 
Protocol deviations 
 
16.2.2.1 
Protocol Deviations  
ITT 
16.2.2.2 
Inclusion/Exclusion Criteria 
Enrolled 
16.2.3 
Subjects excluded from the efficacy analysis 
 
16.2.3.1 
Analysis Populations 
Enrolled 
16.2.4 
Demographic data 
 
16.2.4.1 
Demographic and Baseline Characteristics 
ITT 
16.2.4.2 
Patch Testing Consent/Assent 
Enrolled 
16.2.4.3 
Medical History 
ITT 
16.2.4.4 
Prior and Concomitant Medications 
ITT 
16.2.4.5 
Study Exit Interview Consent/Assent 
Enrolled 
16.2.5 
Compliance and/or drug concentration data  
 
16.2.5.1 
Study Drug Administration 
Safety 
16.2.5.2 
Study Drug Accountability 
Safety 
16.2.5.3 
Dosing Plan and Treatment Modification 
Safety 
16.2.5.4 
Treatment Compliance 
Safety 
16.2.6 
Individual efficacy response data 
 
16.2.6.1 
Lesion Counts 
ITT 
16.2.6.2 
Lesion Count Derived Efficacy Variables and Time to Complete Clearance 
ITT 
16.2.6.3 
Household Transmission 
ITT 
16.2.6.4 
Global Severity Assessment 
ITT 
16.2.6.5 
Global Impression of Change 
ITT 
16.2.6.6 
Patient Reported Outcome of Molluscum Contagiosum Disease Status based on Lost to Follow-up Contact 
ITT 


 
 
 
Novan, Inc.  
                                                                                                 Statistical Analysis Plan 
NI-MC304 
                                                                                                                     24May2021 
 
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ICH Listing 
Number 
 
Listing Title 
Analysis 
Population 
16.2.7 
Adverse events listings 
 
16.2.7.1 
All Adverse Events 
Safety 
16.2.7.2 
Adverse Events Leading to Study Discontinuation 
Safety 
16.2.7.3 
Ongoing Treatment Related Adverse Events 
Safety 
16.2.7.4 
Post Treatment Adverse Events 
Safety 
16.2.8  
Listing of individual laboratory measurements by subject, when required by regulatory authorities 
 
16.2.8.1 
Urine Pregnancy Test 
Safety 
16.2.9 
Other data 
 
16.2.9.1 
Beginning-of-the-End (BOTE) Inflammation Score 
Safety 
16.2.9.2 
Local Skin Reactions (LSR) 
Safety 
16.2.9.3 
Physical Examination 
Safety 
16.2.9.4 
Scarring/Keloid Assessment 
Safety 
16.2.9.5 
Patch Testing 
Safety 
16.2.9.6 
Telephone Contact 
ITT 
16.2.9.7 
Subjects who Require a Narrative  
ITT 
16.2.9.8 
COVDI-19 Impacted Visits 
ITT