Clinical trial NCT03436615
Conditions: Molluscum Contagiosum
Sponsor: Novan, Inc.
Start date: 2018-01-24; Completion date: 2018-11-03
Enrollment: 256 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled ascending dose study to be conducted in non-immunocompromised subjects with molluscum contagiosum.

Detailed description:
This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled ascending dose study to be conducted in up to approximately 192 or 256 non-immunocompromised subjects with molluscum contagiosum. Subjects who satisfy entry criteria will be randomized 3:1 to ascending, sequential dose cohorts of SB206. The highest tolerated dose will also be run in a cohort once daily. Approximately 64 subjects will be randomized to each cohort. Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks. After 30 subjects randomized in a cohort have completed 2 weeks of treatment, the Data Safety Monitoring Board (DSMB) will review the available unblinded safety and tolerability data. The DSMB will determine if the data supports escalating to the next highest dose for the next cohort or if the data shows the dose is not tolerable decreasing to the next lower dose or frequency for the next cohort.

Arms: arm 1: SB206 4% topically twice daily arm 2: SB206 8% topically twice daily arm 3: SB206 12% topically once or twice daily arm 4: Vehicle Gel topically once or twice daily
Interventions: intervention 1: SB206 4% intervention 2: SB206 8% intervention 3: SB206 12% intervention 4: Placebo
Intervention descriptions: intervention 1: Twice daily intervention 2: Twice daily intervention 3: Once or twice daily intervention 4: Once or twice daily

Protocol documents:
SAP_002.pdf: 
Novan, Inc 
Clinical Study Report NI-MC201 
AD-MW-36.03 20-Aug-2018 
CONFIDENTIAL 
16.1.9 
Documentation of Statistical Methods 
Final Statistical Analysis Plan, Version 1.0, dated 17-Aug-2018 
16.1 Study Information
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   Statistical Analysis Plan 
Sponsor 
Novan, Inc. 
Protocol Title: 
A PHASE 2 MULTI-CENTER, RANDOMIZED, DOUBLE-
BLIND, VEHICLE-CONTROLLED, ASCENDING DOSE 
STUDY OF SB206 IN SUBJECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Protocol Number: 
NI-MC201 
Premier Research PCN: 
NOVT177332 
Document Version: 
Final 1.0 
Document Date: 
17-Aug-2018
Approvals 
Role 
Signatures 
Date (dd-Mmm-yyyy) 
Lead 
Biostatistician 
Print Name: Robert M. Flikkema, Ph.D. 
Sign Name: 
Novan, Inc. 
Representative 
Print Name: Todd A. Durham, MS Ph.D. 
Sign Name: 
17-Aug-2018 | 14:52:07 EDT
20-Aug-2018 | 12:51:14 EDT
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 2 of 98 
 
Document History 
Not applicable. 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Table of Contents 
Approvals ...................................................................................................................................................... 1 
Document History ......................................................................................................................................... 2 
Table of Contents .......................................................................................................................................... 3 
List of Tables ................................................................................................................................................ 7 
List of Figures ............................................................................................................................................... 7 
1. 
Overview .......................................................................................................................................... 8 
2. 
Study Objectives and Endpoints ...................................................................................................... 8 
2.1. 
Study Objectives........................................................................................................................ 8 
2.2. 
Study Endpoints ........................................................................................................................ 8 
2.2.1. Safety Endpoints........................................................................................................................ 9 
2.2.2. Efficacy Endpoints .................................................................................................................... 9 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) ...................................................................... 9 
3. 
Overall Study Design and Plan ........................................................................................................ 9 
3.1. 
Overall Design ......................................................................................................................... 10 
3.2. 
Sample Size and Power ........................................................................................................... 10 
3.3. 
Study Population ..................................................................................................................... 10 
3.4. 
Treatments Administered ........................................................................................................ 10 
3.5. 
Method of Assigning Subjects to Treatment Groups .............................................................. 11 
3.6. 
Blinding and Unblinding ......................................................................................................... 11 
3.7. 
Schedule of Events .................................................................................................................. 12 
4. 
Statistical Analysis and Reporting ................................................................................................. 15 
4.1. 
Introduction ............................................................................................................................. 15 
4.2. 
Interim Analysis and Data Monitoring .................................................................................... 15 
5. 
Analysis Populations ...................................................................................................................... 16 
6. 
General Issues for Statistical Analysis ........................................................................................... 16 
6.1. 
Statistical Definitions and Algorithms .................................................................................... 17 
6.1.1. Baseline ................................................................................................................................... 17 
6.1.2. Adjustments for Covariates ..................................................................................................... 17 
6.1.3. Multiple Comparisons ............................................................................................................. 17 
6.1.4. Handling of Dropouts or Missing Data ................................................................................... 17 
6.1.5. Analysis Visit Windows .......................................................................................................... 17 
6.1.6. Pooling of Sites ....................................................................................................................... 18 
6.1.7. Derived Variables .................................................................................................................... 18 
6.1.8. Data Adjustments/Handling/Conventions ............................................................................... 18 
7. 
Study Patients/Subjects and Demographics ................................................................................... 20 
7.1. 
Disposition of Patients/Subjects and Withdrawals .................................................................. 20 
7.2. 
Protocol Violations and Deviations ......................................................................................... 20 
7.3. 
Demographics and Other Baseline Characteristics ................................................................. 20 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
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7.4. 
Exposure and Compliance ....................................................................................................... 21 
8. 
Efficacy Analysis ........................................................................................................................... 21 
8.1. 
Primary Efficacy Analysis ....................................................................................................... 21 
8.2. 
Secondary Efficacy Analysis ................................................................................................... 22 
8.3. 
Exploratory Efficacy Analysis ................................................................................................ 23 
9. 
Safety and Tolerability Analysis .................................................................................................... 24 
9.1. 
Adverse Events ........................................................................................................................ 24 
9.1.1. Adverse Events Leading to Withdrawal .................................................................................. 24 
9.1.2. Deaths ...................................................................................................................................... 25 
9.2. 
Clinical Laboratory Evaluations .............................................................................................. 25 
9.3. 
Vital Signs ............................................................................................................................... 25 
9.4. 
Physical Examination .............................................................................................................. 25 
9.5. 
Local Tolerability Assessments ............................................................................................... 25 
9.6. 
Concomitant Medications ........................................................................................................ 26 
10. 
Changes from Planned Analysis .................................................................................................... 27 
11. 
Other Planned Analysis.................................................................................................................. 27 
12. 
References ...................................................................................................................................... 27 
13. 
Tables, Listings, and Figures ......................................................................................................... 27 
13.1. 
Planned Table Descriptions ..................................................................................................... 29 
13.2. 
Efficacy Data ........................................................................................................................... 31 
13.3. 
Safety Data .............................................................................................................................. 32 
13.4. 
Planned Listing Descriptions ................................................................................................... 34 
13.5. 
Planned Figure Descriptions ................................................................................................... 35 
14. 
Tables, Listings, and Listing Shells ............................................................................................... 37 
14.1. 
Standard Layout for all Tables, Listings, and Figures ............................................................. 37 
14.2. 
Planned Table and Figure Shells ............................................................................................. 39 
Table 14.1.1 Subject Disposition All Subjects ..................................................................................... 39 
Table 14.1.2.1 Demographics and Baseline Characteristics Safety Population ................................... 40 
Table 14.1.2.2 Demographics and Baseline Characteristics mITT Population .................................... 42 
Table 14.1.2.3 Demographics and Baseline Characteristics ITT Population ....................................... 42 
Table 14.1.3 Study Drug Exposure and Compliance Safety Population .............................................. 43 
Table 14.2.1.1 Summary of Lesion Counts mITT Population ............................................................. 44 
Figure 14.2.1.1.1 Mean Change from Baseline in Lesion Count over Time by Treatment Group 
mITT Population ..................................................................................................................... 45 
Figure 14.2.1.1.2 Mean Percent Change from Baseline in Lesion Count over Time by 
Treatment Group mITT Population ......................................................................................... 45 
Table 14.2.1.2 Summary of Lesion Count Responders mITT Population ........................................... 46 
Table 14.2.1.3 Complete Clearance Lesion Count Response by Study Visit and Treatment 
Group ....................................................................................................................................... 47 
Table 14.2.1.4 Proportion of Subjects with at Least a 75% Reduction in Lesion Count from 
Baseline Response by Study Visit and Treatment Group........................................................ 48 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
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Table 14.2.1.5 Change from Baseline in Lesion Count by Study Visit and Treatment ....................... 49 
Table 14.2.1.6 Percent Change from Baseline in Lesion Count by Study Visit and Treatment .......... 50 
Table 14.2.1.7 Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start 
of Dosing mITT Population .................................................................................................... 51 
Figure 14.2.1.7 Kaplan-Meier Plot of Time to Complete Clearance (Days) from Start of Dosing 
mITT Population ..................................................................................................................... 52 
Table 14.2.1.8 Kaplan-Meier Estimates of Time to Sustained Complete Clearance (Days) from 
Start of Dosing mITT Population ............................................................................................ 53 
Figure 14.2.1.8 Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start 
of Dosing mITT Population .................................................................................................... 54 
Table 14.2.1.9 Summary of Increases and Decreases from Baseline in Lesion Count mITT 
Population ................................................................................................................................ 55 
Table 14.2.1.10 Summary of Subjects that Develop New Lesions after Achieving a Lesion 
Count of 0 mITT Population ................................................................................................... 56 
Table 14.2.2.1 Summary of Lesion Counts ITT Population ................................................................ 57 
Figure 14.2.2.1.1 Mean Change from Baseline in Lesion Count over Time by Treatment Group 
ITT Population ........................................................................................................................ 57 
Figure 14.2.2.1.2 Mean Percent Change from Baseline in Lesion Count over Time by 
Treatment Group ITT Population ............................................................................................ 57 
Table 14.2.2.2 Summary of Lesion Count Responders mITT Population ........................................... 57 
Table 14.2.2.3 Complete Clearance Lesion Count Response by Study Visit and Treatment 
Group ....................................................................................................................................... 57 
Table 14.2.2.4 Proportion of Subjects with at Least a 75% Reduction in Lesion Count from 
Baseline Response by Study Visit and Treatment Group........................................................ 57 
Table 14.2.2.5 Change from Baseline in Lesion Count by Study Visit and Treatment ....................... 57 
Table 14.2.2.6 Percent Change from Baseline in Lesion Count by Study Visit and Treatment .......... 58 
Table 14.2.2.7 Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start 
of Dosing ITT Population ........................................................................................................ 58 
Figure 14.2.2.7 Kaplan-Meier Plot of Time to Complete Clearance (Days) from Start of Dosing 
ITT Population ........................................................................................................................ 58 
Table 14.2.2.8 Kaplan-Meier Estimates of Time to Sustained Complete Clearance (Days) from 
Start of Dosing mITT Population ............................................................................................ 58 
Figure 14.2.2.8 Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start 
of Dosing ITT Population ........................................................................................................ 58 
Table 14.2.2.9 Summary of Increases and Decreases from Baseline in Lesion Count ITT 
Population ................................................................................................................................ 58 
Table 14.2.2.10 Summary of Subjects that Develop New Lesions after Achieving a Lesion 
Count of 0 ITT Population ...................................................................................................... 58 
Table 14.2.3.1 Complete Clearance Lesion Count Response by Study Visit and Treatment 
Group ....................................................................................................................................... 59 
Table 14.2.4.1 Complete Clearance Lesion Count Response by Study Visit and Treatment 
Group ....................................................................................................................................... 59 
Table 14.3.1.1 Summary of Treatment Emergent Adverse Events Safety Population ......................... 60 
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Statistical Analysis Plan,  
 
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Table 14.3.1.2 Summary of Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term Safety Population ........................................................................................... 61 
Table 14.3.1.3 Summary of Treatment Emergent Adverse Events by System Organ Class, 
Preferred Term, and Severity Safety Population ..................................................................... 62 
Table 14.3.1.4 Summary of Treatment Emergent Adverse Events by System Organ Class, 
Preferred Term, and Relationship to Study Drug Safety Population....................................... 63 
Table 14.3.1.5 Summary of Serious Treatment Emergent Adverse Events by System Organ 
Class, Preferred Term, and Severity Safety Population .......................................................... 64 
Table 14.3.1.6 Summary of Serious Treatment Emergent Adverse Events by System Organ 
Class, Preferred Term, and Relationship to Study Drug Safety Population ............................ 64 
Table 14.3.2.1 Listing of Serious Adverse Events Safety Population .................................................. 65 
Table 14.3.2.2 Listing of Adverse Events Leading to Study Drug Discontinuation Safety 
Population ................................................................................................................................ 66 
Table 14.3.2.3 Listing of Adverse Events Leading to Death Safety Population .................................. 66 
Table 14.3.5.1.1 Summary of Serum Chemistry Laboratory Results Safety Population ..................... 67 
Table 14.3.5.1.2 Shift of Serum Chemistry Laboratory Results from Baseline Safety Population ..... 68 
Table 14.3.5.2.1 Summary of Hematology Laboratory Results Safety Population ............................. 69 
Table 14.3.5.2.2 Shift of Hematology Laboratory Results from Baseline Safety Population .............. 69 
Table 14.3.5.3 Summary of Methemoglobin Results Safety Population ............................................. 69 
Table 14.3.6.1 Summary of Vital Signs Results Safety Population ..................................................... 69 
Table 14.3.6.2 Summary of Local Tolerability Results Safety Population .......................................... 70 
Table 14.3.6.3 Shift of Local Tolerability Results  Safety Population ................................................. 71 
Table 14.3.6.4 Summary of Concomitant Medications Safety Population .......................................... 72 
14.3. 
Planned Listing Shells ............................................................................................................. 74 
Listing 16.2.1.1 Subject Disposition .................................................................................................... 74 
Listing 16.2.1.2 Inclusion and Exclusion Criteria ................................................................................ 75 
Listing 16.2.1.3 Subject Randomization .............................................................................................. 76 
Listing 16.2.2 Protocol Deviations ....................................................................................................... 77 
Listing 16.2.3 Analysis Populations ..................................................................................................... 78 
Listing 16.2.4.1 Demographics and Baseline Characteristics .............................................................. 79 
Listing 16.2.4.2 Medical History .......................................................................................................... 80 
Listing 16.2.5.1 Study Drug Administration ........................................................................................ 81 
Listing 16.2.5.2 Study Drug Accountability ........................................................................................ 82 
Listing 16.2.6.1 Lesion Counts............................................................................................................. 84 
Listing 16.2.6.2 Lesion Count Derived Efficacy Variables, Time to Complete Clearance and 
75% Reduction from Baseline ................................................................................................. 85 
Listing 16.2.7.1 Adverse Events........................................................................................................... 86 
Listing 16.2.8.1.1 Serum Chemistry Laboratory Results ..................................................................... 87 
Listing 16.2.8.1.2 Hematology Laboratory Results.............................................................................. 88 
Listing 16.2.8.1.3 Methemoglobin Results .......................................................................................... 89 
Listing 16.2.8.2 Pregnancy Test ........................................................................................................... 90 
Listing 16.2.8.3 Vital Signs Results ..................................................................................................... 91 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Listing 16.2.8.4 Local Tolerability Assessment ................................................................................... 92 
Listing 16.2.8.5 Physical Examination ................................................................................................. 93 
Listing 16.2.8.6 Concomitant Medications .......................................................................................... 94 
Listing 16.2.8.7 Photography ............................................................................................................... 95 
Appendix 1: Premier Research Library of Abbreviations........................................................................... 96 
 
List of Tables 
Table 1: Schedule of Assessments .............................................................................................................. 13 
Table 2: Planned Demographic Data Summary Tables .............................................................................. 30 
Table 3: Planned Efficacy Tables ............................................................................................................... 31 
Table 4: Planned Safety Tables ................................................................................................................... 32 
Table 5: Planned Listings ............................................................................................................................ 34 
 
List of Figures 
Figure 1: Standardized Layout .................................................................................................................... 38 
 
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Statistical Analysis Plan,  
Novan, Inc.  
Protocol NI-MC201  
PCN Number NOVT177332
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 8 of 98 
1. 
Overview
This statistical analysis plan (SAP) describes the planned analysis and reporting for Novan, Inc. 
protocol NI-MC201 (a phase 2 multi-center, randomized, double-blind, vehicle-controlled, 
ascending dose study of SB206 in subjects with molluscum contagiosum), version 3.0, dated 29-
Jun-2018. Reference materials for this statistical plan include the protocol and the accompanying 
sample data collection documents. Operational aspects related to collection and timing of 
planned clinical assessments are not repeated in this SAP unless relevant to the planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association2 and the Royal Statistical Society3, 
for statistical practice. 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis presented in the CSR will be clearly identified as such in the 
final CSR. 
The statistical plan described hereafter is an a priori plan. It will be submitted to the file prior to 
the generation of any unblinded inferential or descriptive analyses by the project statistician.  To 
further maintain the integrity of study data, the unblinded data summaries pertaining to Novan, 
Inc. NI-MC201 and occurring prior to final database lock, in support of review and reporting of 
safety, are produced by an unblinded statistician who provided unblinded summaries for the 
DSMB but was otherwise not involved in the management of the study. 
2.
Study Objectives and Endpoints
2.1. 
Study Objectives
This study is being conducted to evaluate the efficacy, safety, and tolerability of SB206 for the 
topical treatment of MC (Molluscum Contagiosum). Results will be used to determine the 
dose(s) for future studies. The study objectives are as follows. 

To evaluate the efficacy of SB206 over vehicle gel for up to 12 weeks of topical
treatment of MC

To evaluate the safety and tolerability of SB206 for up to 12 weeks treatment of MC

To evaluate and determine a safe and efficacious SB206 dose level for future studies
2.2. 
Study Endpoints 
The following endpoints will be assessed during the study. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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2.2.1. Safety Endpoints 
Safety assessments will be performed at scheduled timepoints throughout the study and include 
physical examination, vital signs, standard clinical laboratory testing (hematology, serum 
chemistry), methemoglobin measurement, pregnancy test, tolerability evaluation, concomitant 
medications (CM), and adverse events (AEs). 
2.2.2. Efficacy Endpoints 
2.2.2.1. 
Primary Efficacy Endpoint 
Proportion of subjects achieving complete clearance of all MC at Week 12 (Subjects who 
achieved complete clearance before Week 12 need to maintain complete clearance at 
Week 12) 
2.2.2.2. 
Secondary Efficacy Endpoint(s) 
 Proportion of subjects achieving complete clearance of all MC at each visit 
 Time to first complete clearance of all MC 
 Proportion of subjects achieving at least a 75% reduction from baseline in number of MC 
at each visit 
 Mean change from baseline in number of MC at each visit 
 Mean percent change from baseline in number of MC at each visit 
2.2.2.3. 
Exploratory Efficacy Endpoint(s) 
 Proportion of subjects whose lesion count decreases or, separately, increases from 
baseline at each visit 
 Absolute number of subjects who show new lesions after once achieving complete 
clearance at each visit 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) 
PK sampling and analysis will be conducted on a subset of subjects in Cohorts 3 and 4.  
Descriptive results will be reported in the CSR. 
3. 
Overall Study Design and Plan 
This is a phase 2 multi-center, randomized, double-blind, vehicle-controlled ascending dose 
study to be conducted in up to approximately 192 or 256 non-immunocompromised subjects 
with MC. After obtaining informed consent, subjects who satisfy entry criteria will be 
randomized 3:1 (active: vehicle) to ascending, sequential dose cohorts of SB206. The highest 
tolerated dose will also be run in a cohort once daily. Approximately 64 subjects will be 
randomized to each cohort (see study schematic). At randomization, subjects will be stratified by 
number of lesions at Baseline (3-18; 19-70) and atopic dermatitis (AD) history (with AD history; 
without AD history). A maximum of 16 adult subjects, ages 18 and above, will be randomized 
into each cohort; the remaining subjects will be aged 2-17 years. 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
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Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Subjects will be treated once daily, twice daily or three times a week for up to 12 weeks for all 
lesions identified at Baseline and new lesions that arise during treatment. If a subject clears all 
lesions (confirmed by the Investigator at the next regular scheduled visit), the treatment period 
will end and subjects will be followed for recurrence/new lesions until Week 12/Early 
Termination (ET). Subjects will visit the clinic at Screening, Baseline, Week 1, Week 2, Week 4, 
Week 8, and Week 12/ET. 
After 30 subjects in a cohort have completed 2 weeks of treatment, the data safety monitoring 
board (DSMB) will review the available unblinded safety (methemoglobin, AEs, serious AEs 
(SAEs), lab) and tolerability data. Using predetermined criteria documented in the DSMB 
charter, the DSMB will determine if the data supports escalating to the next highest dose for the 
next cohort or if the data shows the dose is not tolerable, decreasing to the next lower dose or 
frequency for the next cohort.  After 64 subjects are randomized to a cohort, the next cohort will 
be opened. Once a subject is randomized to a cohort, the subject will stay in that cohort.  If a 
subject discontinues treatment, the subject will continue in the study and be followed until Week 
12/ET unless the subject/caregiver withdraws the consent. 
The standard operating procedures of the DSMB will be documented in the DSMB charter, 
including the board’s accountability to Novan. 
3.1. 
Overall Design 
3.2. 
Sample Size and Power 
Approximately 192 subjects, 2 years of age and older, with a minimum of 3 and a maximum of 
70 lesions at baseline will be randomized across a minimum of 3 cohorts. If the third cohort is 
administered 12% BID then up to an additional 64 subjects will be randomized in a fourth 
cohort. This Phase 2 study was not powered for formal statistical comparisons. Each of the 
SB206 active dose groups will be compared to Vehicle gel. No adjustments will be made for 
multiplicity. No imputations will be utilized for safety endpoints. 
3.3. 
Study Population 
The study population will consist of males and females, 2 years of age and older, with a 
minimum of 3 and a maximum of 70 MC at baseline. 
3.4. 
Treatments Administered 
Subjects will be treated once daily, twice daily, or three times a week for up to 12 weeks for all 
lesions identified at baseline and new lesions that arise during treatment. Subjects who satisfy 
entry criteria will be randomized 3:1 (active:vehicle) to ascending, sequential dose cohorts of 
SB206.   
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 11 of 98 
 
Figure 1: Study Schematic 
    Cohort 1                  Cohort 2                  Cohort 3                 Cohort 4 
      (N=64) 
 
   (N=64) 
 
 (N=64) 
         (N=64) 
 
Note: Tolerated (T) or not tolerated (NT) is decided on a cohort basis, not on a subject level, 
after 30 subjects have completed 2 weeks of treatment. 
3.5. 
Method of Assigning Subjects to Treatment Groups 
In this randomized, double-blind, vehicle-controlled study, subjects who meet study entry criteria 
will be randomly assigned in a 3:1 ratio (active: vehicle) to ascending, sequential dose cohorts of 
SB206. The randomization schedule will be computer generated using a permuted block 
algorithm and will randomly allocate IP to randomization numbers. The randomization numbers 
will be assigned sequentially through a central interactive web response system (IWRS) as 
subjects are entered into the study (Cohort 1, then Cohort 2, then Cohort 3, then Cohort 4). 
Randomization will be stratified by number of lesions at baseline (3-18, 19-70) and atopic 
dermatitis history (with AD history vs without AD history). A maximum of 16 adult subjects, 
ages 18 and above, will be randomized into each cohort. 
3.6. 
Blinding and Unblinding 
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. 
A DSMB will conduct an unblinded review of safety and tolerability data after 30 subjects are 
enrolled and treated for 2 weeks within each cohort. Unblinded personnel who are not otherwise 
involved in the study will prepare the data for review. 
Study personnel will endeavor to safeguard the integrity of the study blind to minimize bias in 
the conduct of the study. Unblinding of single events in support of safety reporting will not be 
viewed as introducing study bias and all information of treatment assignment will be limited to 
individuals supporting safety reporting.  
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
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3.7. 
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1. 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
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Table 1: Schedule of Assessments 
Screening1 
(Day -28 to 
Day 1) 
Visit 11 
Baseline 
(Day 1) 
Visit 22 
Week 1 
(Day 8 ±3) 
Visit 32 
Week 2 
(Day 15 ±3) 
Visit 42 
Week 4 
(Day 29 ±3) 
Visit 52 
Week 8 
(Day 57 ±3) 
Visit 62 
Week 12/ET 
(Day 85 ±7) 
Informed Consent (Assent) 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical and Medication History 
X 
X 
 
 
 
 
 
Lesion Counts 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
  
X 
 
  
  
  
X 
Vital Signs 
  
X 
X 
X 
X 
X 
X 
Chemistry & Hematology3 
 
X 
 
  
  
  
X 
Methemoglobin4 
  
X 
X 
X 
X 
X 
X 
Assessment of hMAP3 plasma concentration5,6 
 
 
 
 
 
 
X 
Urine Pregnancy Test7 
X 
X 
 
  
X 
X 
X 
Tolerability Evaluation 
  
X 
X 
X 
X 
X 
X 
Photographs6 
  
X 
 
 
X 
 
X 
In Clinic Study Drug Application and Provide 
Subject Instructions 
 
X 
 
 
 
 
 
Dispense Subject Diary 
 
X 
 
 
X 
X 
 
Review Study Compliance 
 
 
X 
X 
X 
X 
X 
Collect Subject Diary 
 
 
 
 
X 
X 
X 
Drug Dispensed 
 
X 
 
 
X 
X 
 
Collect Study Drug 
 
 
 
 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Review Concomitant Medications and 
Adverse Events  
 
X 
X 
X 
X 
X 
X 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-Aug-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 14 of 98 
 
1 Screening and Baseline may occur on the same day 
2 All visit dates are in reference to Baseline, e.g. Week 1 occurs 7 days after Baseline Visit.   
3 Collected at the last day of treatment. 
4 Collected via pulse co-oximetry at site. 
5 Blood for determination of the hMAP3 plasma concentration will be collected at a single time approximately 1 to 6 hours following last dose application. The 
time of the sample collection and the time of last dose preceding the scheduled visit will be recorded. The blood sample may be collected at the same time as the 
chemistry and hematology sample. 
6 Selected sites and subjects. 
7 Females 10 years of age and older. Subjects whose Baseline visit is within 7 days of Screening do not require UPT retesting. 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 15 of 98 
 
4. 
Statistical Analysis and Reporting 
This SAP is based on the approved clinical study protocol, version 3.0, dated 29-Jun-2018. 
This SAP addresses the safety and efficacy objectives of the study and describes the statistical 
methods that are to be used both for the final analysis of the completed study and the interim 
analysis of data through Cohort 3. 
The reader of this SAP is encouraged to also read the clinical protocol, DSMB charter, and all 
other identified documents, for details on the planned conduct of this study. Operational aspects 
related to collection and timing of planned clinical assessments are not repeated in this SAP 
unless relevant to the planned analysis. 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will be performed primarily using SAS (release 9.4 or higher). If the 
use of other software is warranted, the final statistical methodology report will detail what 
software was used for what purposes. 
Continuous (quantitative) 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 coefficient of variation (%CV), quartiles, confidence intervals (CIs), and 
number of missing values may be added as appropriate.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular 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. 
The minimum and maximum will be reported with the same degree of precision (ie, the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
reported to 1 degree of precision more than the observed data and measures of spread (SD) will 
be reported to 2 degrees of precision more than the observed data. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
Unless otherwise indicated, all statistical tests will be conducted at the 0.05 significance level 
using 2-tailed tests, and P-values will be reported. A P-value of  0.10 but > 0.05 will be 
considered evidence of a trend. Corresponding 95% CIs will be presented for statistical tests. 
 
4.2. 
Interim Analysis and Data Monitoring 
After all subjects in Cohort 3 have completed their last study visits, the database for all subjects 
in Cohorts 1-3 will be frozen for purposes of an interim analysis of safety and efficacy data. All 
statistical outputs planned for the final analysis with the exception of the PK oututs will be 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 16 of 98 
 
generated for the interim analysis. These outputs will exclude any data from Cohort 4 that exists 
in the database. 
As described in Section 3, the DSMB will review the available unblinded safety and tolerability 
data after 30 subjects randomized in a cohort have completed 2 weeks of treatment. On the basis 
of this review, the DSMB will make recommendations to the sponsor about initating the 
subsequent treatment cohort. All responsibilities of the DSMB and details of data to be reviewed 
will be detailed in the DSMB charter. 
The first review will occur when 30 subjects have completed 2 weeks of treatment in cohort 1. 
The second review will occur when 30 subjects have completed 2 weeks of treatment in cohort 2. 
The third review will occur when 30 subjects have completed 2 weeks of treatment in cohort 3. 
The sponsor may request additional reviews, e.g., should any other findings/issues pertaining to 
safety or efficacy emerge requiring DSMB review. Details of the operation of the DSMB will be 
developed in conjunction with the members of the DSMB before the first meeting and will be 
modified as required. 
The unblinded analysis will be performed by an independent statistician other than the author of 
this plan or the person responsible for the primary analysis of this study and treatment codes will 
be revealed to that party only. The DSMB outputs will not be seen by anyone except the DSMB 
and the unblinded statistician. 
5. 
Analysis Populations 
The following analysis populations are planned for this study: 
 Safety Population (SAF): The safety population will consist of all patients who receive 
at least 1 application of study medication. 
 Intent-To-Treat Population (ITT): The ITT population will consist of all subjects who 
are randomized. 
 Modified Intent-To-Treat Population (mITT): The mITT population will consist of all 
subjects who are randomized and complete the study treatment (subjects who complete 
12 weeks of treatment and subjects who complete the treatment period earlier than 12 
weeks, due to clearance of all molluscum). 
 Exposure Population: The exposure population will consist of all subjects who receive 
at least 1 application of SB206 and had a blood sample collected and analyzed for the 
hMAP3 plasma concentration. 
 Per-Protocol Population (PP): The PP population will consist of all subjects in the 
mITT population who have no significant protocol deviations that impact the analyses of 
the efficacy endpoints. 
6. 
General Issues for Statistical Analysis 
Table and figure outputs based on the safety population and all listings will be presented by 
actual treatment received. Table and figure outputs based on the ITT, mITT, or PP populations 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 17 of 98 
 
will be presented by randomized treatment. Unless otherwise stated, table outputs will contain a 
pooled vehicle gel column, a column for each SB206 treatment, and a pooled SB206 column. 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
The last observation recorded prior to the first application of study drug will be used as the 
baseline observation for all calculations of change from baseline. The time of assessment will not 
be collected for the assessments on this study with the exeption of the local tolerability 
assessment at baseline.  For assessments without time, the records collected at the Baseline Day 
1 visit in the database will be used as baseline. If the Baseline Day 1 assessment is missing, then 
the assessment collected at screening will be used unless there is an unscheduled assessment 
after screening and on or before the date of the first application of study drug. If this occurs, the 
unscheduled assessment will be treated as baseline. For the local tolerability assessment, baseline 
will be derived using the dates and times of each assessment and the date and time of first 
application. 
6.1.2. Adjustments for Covariates 
The primary analysis will include the baseline stratificiation variables of number of lesions (3 to 
18; 19 to 70) and atopic dermatitis history (yes/no) as covariates. 
6.1.3. Multiple Comparisons 
No adjustments will be made for multiple comparisons for this study. 
6.1.4. Handling of Dropouts or Missing Data 
For the efficacy analyses, missing data will be imputed for dichotomous outcomes (e.g., clearance 
of all MC) and the continuous outcomes (e.g., lesion counts) using the methods in Section 8, 
Efficacy Analysis. 
6.1.5. Analysis Visit Windows 
In order to summarize data collected over time (including unscheduled visits), the following visit 
windows will be utilized. If multiple assessments fall within a window, the assessment closest to 
the target day will be used. If two assessments are equidistant from the target day, the earliest 
assessment will be used. If a scheduled and unscheduled assessment falls on the same day, the 
scheduled assessment will be used.  
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 18 of 98 
 
 
Analysis Visit 
Target Day 
Time Window 
Baseline 
1 
Day -21 to 1 
Week 1  
8 
Day 2 to 11 
Week 2  
15 
Day 12 to 22 
Week 4  
29 
Day 23 to 43 
Week 8  
57 
Day 44 to 71 
Week 12  
85 
Day 72 or later 
 
6.1.6. Pooling of Sites 
Not applicable. 
6.1.7. Derived Variables 
 Time to complete clearance of all MC (days) = date of first complete clearance of all MC 
– date of first application + 1. Subjects who do not achieve complete clearance prior to 
their last visit will be censored at their last visit date.  
 Time to sustained complete clearance of all MC = date of first complete clearance of all 
MC where subject maintains complete clearance through Week 12 – date of first 
application + 1. Subjects who do not achieve sustained complete clearance prior to their 
last visit will be censored at their last visit date. 
 Change from baseline = value at current time point – value at baseline.  
 Percent change from baseline = 100*change from baseline/value at baseline. 
 Treatment Emergent Adverse Event (TEAE) = any AE with an onset date after the first 
application of study drug. 
6.1.8. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
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All P-values will be displayed in three decimals and rounded using standard scientific notation 
(e.g., 0.XXX). If a P-value less than 0.001 occurs it will be shown in tables as <0.001.  If a P-value 
greater than 0.999 occurs it will be shown in tables as >0.999. 
Adverse events and medical history will be coded using the MedDRA version 20.1 thesaurus. 
Concomitant medications will be coded using World Health Organization Drug Dictionary 
Enhanced (WHO-DDE) (September 2017). 
A treatment related AE is any AE with a relationship to the study drug of definite, probable, or 
possible. 
Missing AE dates will not be imputed. The AE CRF does not allow the study investigators to 
report partial start and end dates, so partial AE date imputation is not required. 
If it is necessary to calculate a subject’s age from the (partial or complete) date of birth and the 
date of Baseline, the floor function will be used to ensure the subject has an integer age. 
If partial medication dates occur, the convention for replacing missing dates for the purposes of 
calculating derived variables is as follows: 
For partial medication start dates: 
 If the year is unknown, then do not impute the date but assign a missing value. 
 If the year is known, but the month or month and day is unknown, then: 
o If the year matches the year of first application date and the end date (if present) is 
after first application date, or medication is ongoing, then impute as the month 
and day of the first application date. If this produces a date after the medication 
end date, assign 01 January. 
o Otherwise, assign 01 January. 
 If the year and month are known, but the day is unknown, then: 
o If the month and year match the month and year of the first application date, then 
impute as the day of the first application date. If this produces a date after the 
medication end date, assign 01. 
o Otherwise, assign 01. 
For partial medication end dates: 
 If the year is unknown, then do not impute the date but assign as missing value. 
 If the year is known but the month or month and day is unknown, then: 
o If the year matches the year of the last date of the study (date of last contact if 
subject lost to follow-up; date of completion or early termination otherwise), then 
impute as the month and day of the last date of the study. 
o Otherwise, assign 31 December. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
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 If the the year and month are known, but day is unknown, then: 
o If the month and year match the month and year of the last date of the study, then 
impute as the day of the last date of the study. 
o Otherwise, assign the last day of the month. 
In general, for quantitative laboratory values reported as ‘<X’ or ‘≤X’, the lower limit of 
quantitation (LLOQ) will be used for analysis (ie, the value of X will be used in the analysis for 
lab values reported as ‘<X’ or ‘≤X’). Similarly, for quantitative laboratory values reported as 
‘>X’ or ‘≥X’, the upper limit of quantitation (ULOQ) will be used for analysis (ie, the value of X 
will be used in the analysis for lab values reported as ‘>X’ or ‘≥X’). 
For analysis purposes, repeat laboratory test results will not be used unless the original 
laboratory value is missing or indicated as invalid, in which case the first non-missing repeated 
laboratory value will be used for data analysis. 
Screen failure data will not be captured in the database. 
7. 
Study Patients/Subjects and Demographics 
7.1. 
Disposition of Patients/Subjects and Withdrawals 
The number of subjects randomized and treated will be summarized by treatment group. The 
number and percentage of subjects who prematurely discontinued treatment, who completed the 
study, and who prematurely discontinued the study will be summarized by treatment group. The 
reasons for treatment and study discontinuation will also be summarized. The number and 
percentage of subjects in the safety, ITT, mITT, Exposure, and PP populations will be 
summarized by treatment group. 
All disposition information will be listed. 
7.2. 
Protocol Deviations 
Protocol deviations will be listed. 
7.3. 
Demographics and Other Baseline Characteristics 
Demographic variables such as age, gender, ethnicity, and race, and baseline characteristics such 
as height, weight, body mass index (BMI), lesion count, and atopic dermatitis history will be 
summarized by treatment group for the safety, ITT, and mITT populations. 
Categorical variables, such as gender, ethnicity, race, and atopic dermatitis history will be 
summarized using frequencies and percentages. Continuous variables such as age, height, 
weight, and BMI will be summarized using mean, standard deviation (SD), median, minimum, 
and maximum. A continuous summary of lesion counts will be presented along with a 
categorical summary of subjects with 3 to 18 or 19 to 70 lesions at baseline. 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
coding system (version 20.1). Medical history information will be listed only. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 21 of 98 
 
Demographic information will be listed. 
7.4. 
Exposure and Compliance 
For all of the below formulas, i = individual subject for the entire treatment period. 
 Total days of exposure will be calculated as: 
∑𝐷𝑎𝑦𝑠 𝑜𝑛 𝑆𝑡𝑢𝑑𝑦 𝐷𝑟𝑢𝑔
𝑖
 
 Study drug compliance will be calculated as: 
∑𝐴𝑐𝑡𝑢𝑎𝑙 𝐴𝑝𝑝𝑙𝑖𝑐𝑎𝑡𝑖𝑜𝑛𝑠 𝐴𝑝𝑝𝑙𝑖𝑒𝑑
𝑖
∑𝑃𝑙𝑎𝑛𝑛𝑒𝑑 𝐴𝑝𝑝𝑙𝑖𝑐𝑎𝑡𝑖𝑜𝑛𝑠
𝑖
× 100 
 
Planned applications is the number planned up to the point of discontinuation. Actual 
applications applied is planned applications minus the number of applications missed. Total days 
of exposure and compliance will be summarized by treatment group. 
Study drug application and compliance information will be listed. All study drug noncompliance 
such as missing applications and interruptions in the schedule of administration will be listed in 
the protocol deviations listing. 
8. 
Efficacy Analysis 
8.1. 
Primary Efficacy Analysis 
The primary efficacy variable for this study is the proportion of subjects achieving complete 
clearance of all MC at Week 12 (subjects who achieve complete clearance before Week 12 need 
to maintain complete clearance at Week 12) for the mITT population.  
Subjects will have their lesion counts measured at Screening, Baseline, Week 1, Week 2, Week 
4, Week 8, and Week 12/ET visits. These and any unscheduled visits will be mapped to Baseline, 
Week 1, Week 2, Week 4, Week 8, and Week 12 analysis visits using the visit windowing 
algorithm described in section 6.1.5. 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 variable will be analyzed using a logistic regression model with treatment, 
number of lesions at baseline (3-18; 19-70), and atopic dermatitis history (with AD history; 
without AD history) as factors. The odds ratios between active treatments and vehicle gel, 95% 
CIs for the odds ratios, and P-values for the differences in treatment will be presented. The 
difference in proportions between active treatments and vehicle gel, 95% CIs for the differences, 
and P-values for the differences in treatment will be presented. The primary analysis will 
compare each SB206 dose level and pooled SB206 with vehicle gel using the mITT population. 
Subjects who discontinue the study before the Week 12 analysis visit (study day 71 or earlier) for 
any reason will be considered not to have achieved complete clearance at Week 12, even if the 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 22 of 98 
 
subject discontinues after a lesion count of 0. In the event of quasi or complete separation, the 
logistic regression model will use Firth’s penalized maximum likelihood estimation. 
The potential for heterogeneity of treatment effects will be assessed by testing treatment-by-
stratum interactions: the logistic regression model for the primary analyses will be expanded to 
include the treatment-by-number of baseline lesions interaction and, separately, the treatment-by-
AD history interaction.  Any evidence of interactions with treatment (e.g., interaction P-value 
≤0.10) will be explored further.        
A sensitivity analysis of the primary analysis will be conducted by repeating the above analysis 
using the following analysis populations: ITT; PP; and the mITT population after excluding 
subjects that have at least one other subject from the same household enrolled in the study.  
8.2. 
Secondary Efficacy Analysis 
The secondary efficacy variables for this study include: 
 Proportion of subjects achieving complete clearance of all MC at each visit 
 Time to complete clearance of all MC 
 Proportion of subjects achieving at least 75% reduction from baseline in number of MC 
at each visit 
 Mean change from baseline in number of MC at each visit 
 Mean percent change from baseline in number of MC at each visit 
The proportion of subjects achieving complete clearance of all MC at each visit will be analyzed 
using the same logistic regression analysis described in Section 8.1 for each of the other visits in 
the study. Complete clearance at visits other than Week 12 is defined as having a lesion count of 
0 on a visit. Subjects with missing lesion counts at a visit for any reason will be counted as not 
clear for that visit. 
Time to first complete clearance of all MC will be analyzed using Kaplan-Meier methods. The 
number of subjects, number and percentage of censored subjects, and Kaplan-Meier estimates of 
first quartile, median, and third quartile as well as the minimum and maximum will be 
summarized by treatment group. Differences in Kaplan-Meier curves between vehicle gel and 
both the SB206 dose levels and pooled SB206 group will be tested for significance using the log-
rank test. Additionally, Kaplan-Meier curves will be presented by treatment group for the mITT 
population. Time to first complete clearance is calculated as date of first complete clearance  – 
first application date + 1. If a subject does not achieve complete clearance while on the study, 
that subject will be censored using the last date on study. 
Time to first sustained complete clearance of all MC will be analyzed using the same Kaplan-
Meier methods used to analyze time to first complete clearance. Time to first sustained clearance 
is calculated as date of first complete clearance (where subject maintains clearance through 
Week 12) – first application date + 1. If a subject does not achieve complete clearance while on 
the study, that subject will be censored using the last date on study. 
Proportion of subjects achieving at least 75% reduction from baseline in number of MC will be 
Page 23


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 23 of 98 
 
analyzed using the same logistic regression analysis as used to analyze the proportion of subjects 
achieving complete clearance of all MC at each visit. 
Mean change and percent change from baseline in number of MC at each visit will be analyzed 
using a mixed-model repeated measures (MMRM) analysis with treatment as the main effect, 
visit, number of lesions at baseline (3-18; 19-70), and atopic dermatitis history (with AD history 
vs without AD history) as factors and treatment by visit as an interaction term. All post-baseline 
analysis visits will be included in the model (Week 1, Week 2, Week 4, Week 8, and Week 12). 
An unstructured covariance matrix will be used to model the within-subject errors. The 
Kenward-Roger approximation will be used to estimate degrees of freedom. 
The least squares (LS) mean change from baseline and percent change from baseline will be 
presented along with the associated 95% CI within each SB206 treatment, pooled SB206, and 
vehicle gel group. In comparing treatments (SB206 minus vehicle gel), LS mean differences in 
change from baseline will be presented along with associated 95% CIs and pairwise treatment P-
values.  
In case of convergence issues, other covariance structures will be used including (but not limited 
to) autoregressive (AR(1)), compound symmetry (CS), and variance components (VC) with each 
model fit to find the covariance structure with the best fit. The fit statistics will be compared for 
all covariance structures; the structure with the smallest Akaike information criterion will be 
retained as the preferred model. 
Two separate MMRM models will be run, the first comparing the individual SB206 treatments 
with vehicle gel, and the second comparing the pooled SB206 treatment group with vehicle gel. 
Mean change and mean percent change from baseline in number of MC at each visit will be 
plotted over time by SB206 treatment, pooled SB206, and vehicle gel. 
All secondary efficacy analyses will be conducted on the mITT and ITT population. 
8.3. 
Exploratory Efficacy Analysis 
The exploratory efficacy variables for this study include: 
 Proportion of subjects whose lesion count decreases and increases from baseline at each 
visit 
 Absolute number of subjects who show new lesions after once achieving a lesion count of 
0 at each visit 
The frequency and percentage of subjects at each visit who had an increase, decrease, and no 
change in lesion count from baseline will be summarized by treatment group. 
The frequency and percentage of subjects at each visit and overall who show new lesions after 
once achieving a lesion count of zero, subjects with a lesion count of 0, and subjects with a 
lesion count of 0 at a prior visit will be summarized by treatment group. 
The exploratory efficacy analyses will be conducted on the mITT population. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
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9. 
Safety and Tolerability Analysis 
Safety assessments will be performed at scheduled timepoints throughout the study and include 
physical examination, vital signs, standard clinical laboratory testing (hematology, serum 
chemistry), methemoglobin measurement, pregnancy test, tolerability evaluation, CMs, and AEs. 
All safety analyses will be performed on the Safety population by actual treatment received. 
9.1. 
Adverse Events 
Adverse events will be coded using the MedDRA coding thesaurus (version 20.1). Treatment-
emergent AEs (TEAEs) will be summarized in all tables. A TEAE is defined as an AE with onset 
on or after the date of the first application of study drug. Medical histories noted prior to the first 
study drug administration that worsen after baseline will also be reported as TEAEs and included 
in the summaries. All AE summary tables will include the number and percentage of subjects as 
well as the total number of AEs within a category, system organ class (SOC), or preferred term 
(PT). 
An overall summary of the number and percentage of subjects with TEAEs will be provided by 
treatment group. Frequencies and percentages of the following will be included: subjects with any 
TEAE, subjects with a related TEAE, subjects with any TEAE leading to discontinuation, subjects 
with any TEAE leading to death, and subjects with any serious treatment-emergent AE (SAE). 
The incidence of TEAEs will be summarized with frequencies and percentages by the following: 
 SOC and PT 
 SOC, PT, and maximum severity 
 SOC, PT, and relationship to study drug 
 SAEs by SOC, PT, and maximum severity 
 SAEs by SOC, PT, and relationship to study drug 
Incidences will be presented alphabetically by SOC and PT. TEAEs with a missing severity will 
be considered severe and TEAEs with a missing relationship will be considered related. 
All adverse events will be presented in a listing. 
9.1.1. Adverse Events Leading to Withdrawal 
A data listing of AEs leading to withdrawal of study drug will also be provided, displaying 
details of the event(s) captured on the CRF. 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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9.1.2. Deaths 
Any deaths that occur during the study will be listed. 
9.2. 
Clinical Laboratory Evaluations 
Screening and safety chemistry and hematology tests will be performed at Baseline and Week 12 
(for subjects who completed the study before Amendment 2) or at the visit corresponding to the 
last treatment application (for subjects who had not yet completed the study at the time of 
Amendment 2). All laboratory values will be mapped to the closest study visit, as defined in 6.1.5. 
Methemoglobin measurements will be collected at Baseline, Week 1, Week 2, Week 4, Week 8, 
and Week 12. All summaries of laboratory units will be presented using the International System 
of Units (SI). Observed values and change from baseline at each visit will be summarized by 
treatment group. Shifts from Baseline to Week 1, Week 2, Week 4, Week 8, and Week 12 for 
chemistry and hematology results will also be summarized by treatment group.  Clinically 
significant abnormal findings will be reported as AEs. 
Chemistry, hematology, and methemoglobin results will be listed by subject and timing of 
collection. Values falling outside the normal range for chemistry and hematology will be flagged 
in the listing. 
Pregnancy test results will be listed. 
9.3. 
Vital Signs 
Descriptive summaries of observed values and changes from baseline will be calculated for 
systolic blood pressure (mmHg), diastolic blood pressure (mmHg), and heart rate. Vital signs 
results will be collected at Baseline, Week 1, Week 2, Week 4, Week 8, and Week 12. Vital 
signs results will be listed. 
9.4. 
Physical Examination 
Physical examination results will be listed only. 
9.5. 
Local Tolerability Assessments 
Subjects will be assessed at 30 minutes post-application on Baseline and at Week 1, Week 2, 
Week 4, Week 8, and Week 12 for local tolerability. The investigator will assess the presence 
and overall degree of irritation (dryness, erythema, and peeling) at the application sites and the 
score will reflect what the investigator sees at the time of the assessment. The score will 
represent an “average” across all application sites. Scores of 3 or 4 will be reported as an AE. 
Investigator Assessment of Dryness, Erythema, and Peeling 
Score Severity 
Description 
0 
No irritation 
No evidence of local irritation/intolerance 
Page 26


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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 Page 26 of 98 
 
1 
Mild 
Minimal erythema and/or edema, slight glazed appearance 
2 
Moderate 
Definite erythema and/or edema with peeling and/or cracking but does not 
require treatment modification 
3 
Severe  
(report as an AE) 
Erythema, edema glazing with fissures, few vesicles or papules 
4 
Very severe 
(report as an AE) 
Strong reaction spreading beyond the treated area, bullous reaction, erosions 
At the Baseline visit, 30 minutes post-application, the subject will be asked to rate the overall 
severity of their itching and burning/stinging. The assessment will apply only to the time since 
application of study drug. At Week 1, Week 2, Week 4, Week 8, and Week 12, the subject will 
be asked to rate the overall severity of their itching and burning/stinging at the treatment areas 
since their previous visit. Scores of 4 will be reported as an AE. 
Subject Assessment of Burning/Stinging and Itching 
Score 
Severity 
Description 
0 
None 
Normal, no discomfort 
1 
Slight 
An awareness, but no discomfort and no intervention required 
2 
Mild 
A noticeable discomfort that causes intermittent awareness 
3 
Moderate 
A noticeable discomfort that causes intermittent awareness and 
interferes occasionally with normal daily activities 
4 
Strong/Severe A definite continuous discomfort that interferes with normal daily 
activities 
The frequencies and percentages of investigator and subject tolerability assessments at each visit 
will be summarized by treatment group. The vehicle gel treatment group will be split into once 
daily (QD), twice daily (BID), and overall groups for this analysis. The frequencies and 
percentages of investigator and subject tolerability assessments at each visit and in relation to 
baseline will be tabulated in a shift table by treatment group. Tolerability assessment results will 
be listed. 
9.6. 
Concomitant Medications 
Concomitant medications will be coded using World Health Organization Drug Dictionary 
Enhanced (WHO-DDE) (Version September 01, 2017 or later) thesaurus. 
Frequencies and percentages of medications used in the study will be summarized as follows: 
 
Page 27


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 27 of 98 
 
 Concomitant medication: a medication with a start date on or after the date of first 
application of study drug (even if end date is missing) and on or before the last 
application of study drug, or medications with a start date before the first application of 
study drug that are ongoing or with a stop date on or after the first application of study 
drug, will be considered concomitant. If medication dates are incomplete and it is not 
clear whether the medication was concomitant, it will be assumed to be concomitant. 
Details of CMs will be listed by subject, start date, and verbatim term.  All medications will be 
summarized by Anatomic Therapeutic Chemical (ATC) class Level 3 and PT. Furthermore, CMs 
will be summarized by treatment group. Subjects will be counted once for each ATC and PT. 
10. 
Changes from Planned Analysis 
Not applicable. 
11. 
Other Planned Analysis 
11.1. Pharmacokinetic Analysis 
Plasma concentrations of hMAP3 collected in Cohorts 3 and 4 will be listed. Analysis will be 
limited to subjects receiving active (SB206) treatment.  If quantifiable concentrations are 
observed, the results will be summarized at Week 12 or at the end of treatment for subjects with 
complete clearance prior to Week 12 using descriptive statistics including number (n), mean, 
standard deviation, median, maximum, minimum, % coefficient of variation (CV), and geometric 
mean. All values below the limit of quantification (BLQ) will be set to 0 for the summary 
statistics. 
12. 
References 
1. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998. 
2. ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2016. http://www.amstat.org/about/ethicalguidelines.cfm  
3.  The Royal Statistical Society: Code of Conduct, 2014. 
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf. 
13. 
Tables, Listings, and Figures 
This section presents the shells for the planned Tables, Listings, and Figures (TLFs) to be 
programmed. This section provides guidance on the programming specifications (shells) for the 
planned outputs. After the programming begins, it may be necessary to modify table titles or 
footnotes or the ordering of rows or columns. Minor, cosmetic changes such as these will not 
require a modification to the final SAP.  
Page 28


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 28 of 98 
 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize the presentation with 
common notations. 
 
 
Page 29


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 29 of 98 
 
General Reporting Conventions 
 All tables and data listings will be developed in landscape orientation. 
 Header and footer rows for tables will repeat on all pages of the table. 
 Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text 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 should be used in tables and data listings. Special 
characters, such as nonprintable control characters, printer-specific characters, or font 
specific characters, will not be used on a table, figure, or data listing. 
 A blank row will be included between subjects in the listings. 
 In the listings, if text will be repeated on multiple rows for a subject, it will only be 
displayed in the first row. If the repeated rows cover multiple pages, the text will also be 
displayed in the first row of each new page. 
 Data collected from subjects that did not receive study drug will be listed only. 
 Programming notes may be inserted into the shells, these notes will not appear in the final 
output. 
 
Population Summary Conventions 
 Population sizes may be presented for each classification factor as totals in the column 
header as (N=xxxx), where appropriate.  
 All population summaries for categorical variables will include all categories that were 
planned and for which the subjects may have had a response. Percentages corresponding 
to null categories (cells) will be suppressed; however, counts and percentages of missing 
values may be needed. 
 All population summaries for continuous variables will include: N, mean, SD, median, 
minimum, and maximum. Other summaries (e.g., number missing, geometric mean, 
median, quartiles, 95% CIs, and coefficient of variation [CV] or % CV) may be used as 
appropriate.  The precision of the maximum and minimum will match the maximum 
precision in the data.  The mean and median will have one additional decimal place. The 
SD will have two additional decimal places. 
 All percentages are rounded and reported to a single decimal point (xx.x %) 
13.1. Planned Table Descriptions 
The following are planned summary tables for protocol number NI-MC201. The table numbers 
and page numbers are place holders only and will be determined when the tables are produced. 
Page 30


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 30 of 98 
 
Table 2: Planned Demographic Data Summary Tables 
Table Number 
Table Title/Summary 
13.1 Demographic Data Summary Tables and Figures 
Table 14.1.1 
Subject Disposition, All Subjects 
Table 14.1.2.1 
Demographics and Baseline Characteristics, Safety Population 
Table 14.1.2.2 
Demographics and Baseline Characteristics, mITT Population 
Table 14.1.2.3 
Demographics and Baseline Characteristics, ITT Population 
Table 14.1.3 
Study Drug Exposure and Compliance, Safety Population 
 
 
Page 31


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
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13.2. Efficacy Data 
Table 3: Planned Efficacy Tables 
Table Number 
Table Title / Summary 
Table 14.2.1.1 
Summary of Lesion Counts, mITT Population 
Table 14.2.1.2 
Summary of Lesion Count Responders, mITT Population 
Table 14.2.1.3      Complete Clearance Lesion Count Response by Study Visit and Treatment Group, 
                             Logistic Regression, mITT Population 
Table 14.2.1.4      Proportion of Subjects with at least a 75% Reduction in Lesion Count from Baseline  
                             Response by Study Visit and Treatment Group, Logistic Regression, mITT Population 
Table 14.2.1.5      Change from Baseline in Lesion count by Study Visit, MMRM, mITT Population 
Table 14.2.1.6      Percent Change from Baseline in Lesion Count by Study Visit and Treatment, MMRM, 
                             mITT Population 
Table 14.2.1.7      Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start of  
                             Dosing, mITT Population 
Table 14.2.1.8      Kaplan-Meier Estimates of Time to First Sustained Clearance (Days) from Start of 
                             Dosing, mITT Population 
Table 14.2.1.9      Summary of Increases and Decreases from Baseline in Lesion Count, mITT Population 
Table 14.2.1.10   Summary of Subjects that Develop New Lesions after Achieving a Lesion Count of 0, 
                             mITT Population 
Table 14.2.2.1 
Summary of Lesion Counts, ITT Population 
Table 14.2.2.2 
Summary of Lesion Count Responders, ITT Population 
Table 14.2.2.3      Complete Clearance Lesion Count Response by Study Visit and Treatment Group, 
                             Logistic Regression, ITT Population 
Table 14.2.2.4      Proportion of Subjects with at least a 75% Reduction in Lesion Count from Baseline  
                             Response by Study Visit and Treatment Group, Logistic Regression, ITT Population 
Table 14.2.2.5      Change from Baseline in Lesion count by Study Visit, MMRM, ITT Population 
Table 14.2.2.6      Percent Change from Baseline in Lesion Count by Study Visit and Treatment, MMRM, 
                             ITT Population 
Table 14.2.2.7      Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start of  
                             Dosing, ITT Population 
Table 14.2.2.8      Kaplan-Meier Estimates of Time to First Sustained Clearance (Days) from Start of 
                                            Dosing, ITT Population 
 
 
Page 32


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 32 of 98 
 
Table Number 
Table Title / Summary 
Table 14.2.2.9      Summary of Increases and Decreases from Baseline in Lesion Count, ITT Population 
Table 14.2.2.10     Summary of Subjects that Develop New Lesions after Achieving a Lesion Count of 0, 
                             ITT Population 
Table 14.2.3.1      Complete Clearance Lesion Count Response by Study Visit and Treatment Group, 
                             Logistic Regression, PP Population 
Table 14.2.4.1      Complete Clearance Lesion Count Response by Study Visit and Treatment Group, 
                             Logistic Regression, Excluding Subjects from Same Household, mITT Population 
 
13.3. Safety Data 
Table 4: Planned Safety Tables 
Table Number 
Table Title / Summary 
14.3.1 Displays of Adverse Events 
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events, Safety Population 
Table 14.3.1.2      Summary of Treatment Emergent Adverse Events by System Organ Class and 
                             Preferred Term, Safety Population 
Table 14.3.1.3      Summary of Treatment Emergent Adverse Events by System Organ Class, 
                             Preferred Term, and Severity, Safety Population 
Table 14.3.1.4      Summary of Treatment Emergent Adverse Events by System Organ Class,  
                             Preferred Term, and Relationship to Study Drug, Safety Population 
Table 14.3.1.5      Summary of Serious Treatment Emergent Adverse Events by System Organ  
                            Class, Preferred Term, and Severity, Safety Population 
Table 14.3.1.6     Summary of Serious Treatment Emergent Adverse Events by System Organ  
                            Class, Preferred Term, and Relationship to Study Drug, Safety Population 
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events 
 
Table 14.3.2.1 
Listing of Serious Adverse Events, Safety Population 
Table 14.3.2.2     Listing of Adverse Events Leading to Study Drug Discontinuation, Safety  
                            Population  
Table 14.3.2.3     Listing of Adverse Events Leading to Death, Safety Population  
Page 33


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 33 of 98 
 
Table Number 
Table Title / Summary 
              14.3.5 Laboratory Data Summary Tables 
Table 14.3.5.1.1 Summary of Serum Chemistry Laboratory Results, Safety Population 
Table 14.3.5.1.2 Shift of Serum Chemistry Laboratory Results from Baseline, Safety Population 
Table 14.3.5.2.1 Summary of Hematology Laboratory Results, Safety Population 
Table 14.3.5.2.2 Shift of Hematology Laboratory Results from Baseline, Safety Population 
Table 14.3.5.3 
Summary of Methemoglobin Results, Safety Population 
14.3.6 Other Safety Data Summary Tables 
Table 14.3.6.1 
Summary of Vital Signs Results, Safety Population 
Table 14.3.6.2 
Summary of Local Tolerability Results, Safety Population 
Table 14.3.6.2      Shift of Local Tolerability Results, Safety Population 
Table 14.3.6.4 
Summary of Concomitant Medications, Safety Population 
Page 34


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 34 of 98 
 
13.4. Pharmacokinetic Data 
Table 5: Planned Pharmacokinetic Tables 
Table Number 
Table Title / Summary 
14.4 Pharmacokinetic Data Summary Tables 
Table 14.4.1 
Summary of hMAP3 Plasma Concentrations  
 
13.5. Planned Listing Descriptions 
The following are planned data and patient/subject data listings for protocol number NI-MC201.  
In general, one listing will be produced per CRF domain. All listings will be sorted by treatment, 
site, and subject number. All calculated variables will be included in the listings. 
In all listings a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (e.g., repetition of subject number), then only the first occurrence will be 
displayed. 
In data listings, the information for one subject will be kept on one page if at all possible, rather 
than splitting a subject’s information across pages. 
Table 6: Planned Listings 
Data Listing Number 
Data Listing Title / Summary 
16.2 Patient/Subject Data Listings 
16.2.1 Patient/Subject Discontinuations/Completions 
Data Listing 16.2.1.1 
Subject Disposition 
Data Listing 16.2.1.2 
Inclusion and Exclusion Criteria 
Data Listing 16.2.1.3 
Subject Randomization 
16.2.2 Protocol Deviations 
Data Listing 16.2.2 
Protocol Deviations 
16.2.3 Patients/Subjects Excluded from the Efficacy Analyses 
Data Listing 16.2.3 
Analysis Populations 
16.2.4 Demographic Data and Other Baseline Characteristics 
Data Listing 16.2.4.1 
Demographic and Baseline Information 
Data Listing 16.2.4.2 
Medical History 
16.2.5 Compliance and/or Drug Concentration Data 
Data Listing 16.2.5.1 
Study Drug Administration 
Page 35


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Data Listing Number 
Data Listing Title / Summary 
Data Listing 16.2.5.2 
Study Drug Accountability 
Data Listing 16.2.5.3          Pharmacokinetic Blood Concentrations 
16.2.6 Individual Efficacy Response Data 
Data Listing 16.2.6.1 
Lesion Counts 
Data Listing 16.2.6.2         Lesion Count Derived Efficacy Variables, Time to Complete Clearance and  
                                           75% Reduction from Baseline 
16.2.7 Adverse Event Listings (by Patient/Subject) 
Data Listing 16.2.7.1 
Adverse Events 
16.2.8 Clinical Observations and Measurements (by Patient/Subject) 
Data Listing 16.2.8.1.1 
Serum Chemistry Laboratory Results 
Data Listing 16.2.8.1.2 
Hematology Laboratory Results 
Data Listing 16.2.8.1.3 
Methemoglobin Results 
Data Listing 16.2.8.2 
Pregnancy Test 
Data Listing 16.2.8.3 
Vital Signs Results 
Data Listing 16.2.8.4 
Local Tolerability Assessment 
Data Listing 16.2.8.5 
Physical Examination 
Data Listing 16.2.8.6 
Concomitant Medications 
Data Listing 16.2.8.7 
Photography 
13.6. Planned Figure Descriptions 
The following are planned summary figures for protocol number NI-MC201. The figure numbers 
and page numbers are place holders only and will be determined when the figures are produced. 
Page 36


 
Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0    |    17-AUG-2018   |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 36 of 98 
 
Table 6: Planned Figures 
Figure Number 
Figure Title / Summary 
Figure 14.2.1.1.1 Mean Change from Baseline in Lesion Count over Time by Treatment Group, mITT   
                             Population 
Figure 14.2.1.1.2 Mean Percent Change from Baseline in Lesion Count over Time by Treatment Group,  
                             mITT Population 
Figure 14.2.1.7     Kaplan-Meier Plot of Time to First Complete Clearance (Days) from Start of Dosing, 
                              mITT Population 
Figure 14.2.1.8     Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start of  
                             Dosing, mITT Population 
Figure 14.2.2.1.1 Mean Change from Baseline in Lesion Count over Time by Treatment Group, ITT  
                             Population 
Figure 14.2.2.1.2 Mean Percent Change from Baseline in Lesion Count over Time by Treatment Group,  
                             ITT Population 
Figure 14.2.2.7     Kaplan-Meier Plot of Time to First Complete Clearance (Days) from Start of Dosing, 
                              ITT Population 
Figure 14.2.2.8     Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start of  
                             Dosing, ITT Population 
Page 37


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 37 of 98 
 
 
14. 
Tables, Listings, and Listing Shells 
14.1. 
Standard Layout for all Tables, Listings, and Figures 
 
 
Page 38


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 38 of 98 
 
 
Figure 1: Standardized Layout 
The following standard layout will be applied to all TLFs in support of this study. Note that programming notes may be added if 
appropriate after each TLF shell. These notes will not appear on the output. 
Novan, Inc 
Page 1 of x 
 
Protocol: NI-MC201 
<version> 
 
<Table, Listing, Figure> xx.x.x 
<Title of Table Listing or Figure> 
<Study Population and if applicable subgroup Description> 
 
 
 
Body of Table, Listing or Figure 
 
 
Note: <Note: If directly Applicable> 
[1] Footnote 1 <if applicable> 
[2] Footnote 2 <if applicable> 
[n] Footnote n <if applicable> 
….\...\xxxx.sas run on DDMMMYYYY at HH:MM on data extracted on DDMMMYY
Page 39


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 39 of 98 
 
 
14.2. 
Planned Table and Figure Shells 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.1.1 
Subject Disposition 
All Subjects 
 
 
 
SB206 
 
Status 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
All SB206 
Overall 
 
 
 
 
 
 
 
 
Safety Population [1] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
ITT Population [2] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
mITT Population [3] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
Exposure Population [4] 
0 
0 
0 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
PP Population [5] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prematurely Discontinued Treatment 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
     Reason for Discontinuation: 
 
 
 
 
 
 
 
          Adverse Event 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Withdrawal by Subject 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Physician Decision 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Protocol Violation 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Lost to Follow-up 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Pregnancy 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Lack of Efficacy 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Other 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
Completed Study 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
Prematurely Discontinued Study 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
     Reason for Discontinuation: 
 
 
 
 
 
 
 
          Withdrawal by Subject/caregiver 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
          Lost to Follow-up 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects treated. The denominator for percentage corresponds to the number of subjects in the safety population. 
[1] The Safety Population consists of all subjects who are administered study drug. 
[2] The Intent-To-Treat Population (ITT) consists of all subjects who are randomized. 
[3] The Modified Intent-to-Treat Population (mITT) consists of all subjects who are randomized and complete the study treatment. 
[4] The Exposure Population consists of all subjects who received any study drug and had a blood sample collected and analyzed for the hMAP3 plasma concentration. 
[5] The Per-Protocol Population (PP) consists of all subjects in the mITT population who have no significant protocol deviations that impact the analyses of the efficacy endpoints. 
SOURCE: Listings 16.2.1.1, 16.2.1.2, and 16.2.1.3 
 
Page 40


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 40 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.1.2.1 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
SB206 
Variable 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Statistic or Category 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Age (years) 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Gender 
 
 
 
 
 
 
   Female 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Male 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
 
   Hispanic or Latino 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Not Hispanic or Latino 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Race 
 
 
 
 
 
 
   American-Indian or Alaska Native 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Asian 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Black or African-American 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Native Hawaiian or Other Pacific Islander 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   White 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Other 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   More than One Race 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Height (cm) 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Age is calculated from the date of birth to the date of informed consent. Baseline is defined as the last measurement taken on or before the date of first application of study drug. 
SOURCE: Listing 16.2.4.1 
 
 
 
 
 
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<Version> 
Table 14.1.2.1 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
SB206 
Variable 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Statistic or Category 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Weight (kg) 
XX 
XX 
XX 
XX 
XX 
XX 
   n 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Std Dev 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Median 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
   Min, Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI (kg/m2) 
XX 
XX 
XX 
XX 
XX 
XX 
   n 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Std Dev 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Median 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
   Min, Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lesion Counts at Baseline 
XX 
XX 
XX 
XX 
XX 
XX 
   n 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Std Dev 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Median 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
   Min, Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lesion Counts at Baseline 
 
 
 
 
 
 
   3 to 18 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   19 to 70 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Atopic Dermatitis History? 
 
 
 
 
 
 
   Yes 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment 
received. Age is calculated from the date of birth to the date of informed consent. Baseline is defined as the last measurement taken on or before the date of first application of 
study drug. 
SOURCE: Listing 16.2.4.1 
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Table 14.1.2.2 
Demographics and Baseline Characteristics 
mITT Population 
 
Table 14.1.2.3 
Demographics and Baseline Characteristics 
ITT Population 
 
 
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<Version> 
Table 14.1.3 
Study Drug Exposure and Compliance 
Safety Population 
 
 
 
SB206 
Variable 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Total Exposure (days) 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Compliance (%) [1] 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
[1] Compliance is defined as the total number of actual applications applied divided by total number of planned applications *100, summed up over the entire treatment period (up to 
treatment completion or discontinuation). 
SOURCE: Listing 16.2.5.1, 16.2.5.2.1, 16.2.5.2.2 
 
 
 
 
 
 
 
 
 
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<Version> 
Table 14.2.1.1 
Summary of Lesion Counts 
mITT Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
  Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Week 1 Observed 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Week 1 Change from Baseline 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
Week 1 Percent Change from Baseline 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
…Continue for other visits. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the mITT population. Subjects are summarized by randomized treatment. Baseline is defined as the last measurement taken on or before the 
date of first application of study drug. 
SOURCE: Listing 16.2.6.1 
 
 
 
 
 
 
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Figure 14.2.1.1.1 
Mean Change from Baseline in Lesion Count over Time by Treatment Group 
mITT Population 
Programming Note: x-axis will read “Study Visit (Week), y-axis will read “Mean Change from Baseline in Lesion Count”.  Curves for vehicle gel, individual active SB206 groups, and a 
pooled SB206 group will be presented.  Footnote will read “Note: Subjects are summarized by randomized treatment. SOURCE: Listing 16.2.6.1. 
 
Figure 14.2.1.1.2 
Mean Percent Change from Baseline in Lesion Count over Time by Treatment Group 
mITT Population 
Programming Note: x-axis will read “Study Visit (Week), y-axis will read “Mean Percent Change from Baseline in Lesion Count”.  Curves for vehicle gel, individual active SB206 
groups, and a pooled SB206 group will be presented.  Footnote will read “Note: Subjects are summarized by randomized treatment. SOURCE: Listing 16.2.6.1. 
 
 
 
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<Version> 
Table 14.2.1.2 
Summary of Lesion Count Responders 
mITT Population 
 
Study Visit 
 
SB206 
   Variable 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
     Statistic or Category 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 1 
 
 
 
 
 
 
   Complete Clearance [1] 
 
 
 
 
 
 
     Yes 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
     No 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
  75% Reduction from Baseline [2] 
 
 
 
 
 
 
    Yes 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    No 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
   Complete Clearance [1] 
 
 
 
 
 
 
     Yes 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
     No 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
  75% Reduction from Baseline [2] 
 
 
 
 
 
 
    Yes 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    No 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
…Continue for Week 4, Week 8, and Week 12. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the number of subjects with a lesion count measurement at each visit. N is the number of subjects in the mITT population. 
Subjects are summarized by randomized treatment. 
[1] Complete clearance is defined as a subject having a lesion count of 0 at a visit. 
[2] At least a 75% reduction in lesion counts from the Baseline visit. Baseline is defined as the last measurement taken on or before the date of first application of study drug. 
SOURCE: Listing 16.2.6.1, 16.2.6.2 
 
 
 
 
 
 
 
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<Version> 
Table 14.2.1.3 
Complete Clearance Lesion Count Response by Study Visit and Treatment Group 
Summary of Fitted Point Estimates from Logistic Regression 
mITT Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 1 
 
 
 
 
 
 
   n [1] 
XX 
XX 
XX 
XX 
XX 
XX 
   Responders [2] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Odds Ratio (SB206 vs Vehicle Gel) 
 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
   95% CI for Odds Ratio 
 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
   p-value [3] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
   Difference in Proportion (SB206 vs Vehicle Gel) 
 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
   95% CI for Proportion Difference 
 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
   p-value [3] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
   n [1] 
XX 
XX 
XX 
XX 
XX 
XX 
   Responders [2] 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Odds Ratio (SB206 vs Vehicle Gel) 
 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
   95% CI for Odds Ratio 
 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
   p-value [3] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
   Difference in Proportion (SB206 vs Vehicle Gel) 
 
X.XX 
X.XX 
X.XX 
X.XX 
X.XX 
   95% CI for Proportion Difference 
 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
   p-value [3] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
Continue for Week 4, Week 8, and Week 12. If Firth’s penalized maximum likelihood is used, add ‘Firth’s penalized maximum likelihood estimation is used.’ to end of 
‘Note:’ footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: OR = Odds ratio. 
Note: The denominator for percentage corresponds to the number of subjects with a lesion count measurement at each visit. N is the number of subjects in the mITT population. 
Subjects are summarized by randomized treatment. 
[1] Number of subjects with a lesion count measurement at each visit. 
[2] Number of subjects with complete clearance at a visit. Complete clearance is defined as a subject having a lesion count of 0 at a visit. 
[3] Estimates for odds ratio, 95% CI for odds ratio, and p-value are from a logistic regression model, with factors for treatment, number of lesions at baseline (3-18; 19-70), and atopic 
dermatitis history (with AD history; without AD history) as factors. Baseline is defined as the last measurement taken on or before the date of first application of study drug. The odds 
ratio is the estimate of the odds of having complete clearance for subjects treated with SB206 relative to that for subjects treated with vehicle gel. 
SOURCE: Listing 16.2.6.1, 16.2.6.2 
 
 
 
 
 
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Table 14.2.1.4 
Proportion of Subjects with at Least a 75% Reduction in Lesion Count from Baseline Response by Study Visit and Treatment Group 
Tabulation of Fitted Point Estimates from Logistic Regression 
mITT Population 
Same shell as 14.2.1.3, update [2] footnote to: [2] Number of subjects with at least a 75% reduction in lesion count from the ‘Baseline’ visit. 
 
 
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Table 14.2.1.5 
Change from Baseline in Lesion Count by Study Visit and Treatment 
Adjusted (Least Squares) Means from MMRM 
mITT Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Statistic [1] 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 1 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   LS Mean Change from Baseline (SE) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
   (95% CI for LS Mean) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
 
 
 
 
 
 
 
   LS Mean Difference in CFB from Vehicle (SE) 
 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
     (95% CI for Difference in CFB from Vehicle) 
 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
   P-value for Difference in CFB from Vehicle [2] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
   LS Mean Change from Baseline (SE) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
   (95% CI for LS Mean) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
 
 
 
 
 
 
 
   LS Mean Difference in CFB from Vehicle (SE) 
 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
XX.X (X.XX) 
     (95% CI for Difference in CFB from Vehicle) 
 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
   P-value for Difference in CFB from Vehicle [2] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
Continue for Week 4, Week 8, and Week 12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: CFB = Change from baseline. 
Note: N is the number of subjects in the mITT population. Subjects are summarized by randomized treatment. Baseline is defined as the last measurement taken on or before the date 
of first application of study drug. 
[1] Estimates for LS means (at Baseline and Study Visit, change from baseline, and difference from vehicle [ie. change from baseline for SB206 minus change from baseline for 
vehicle gel]), 95% CI for mean diference from vehicle gel, and P-value for difference from vehicle gel are from a mixed model for repeated measures (MMRM) with treatment, study 
visit, and treatment-by-study visit interaction as fixed effects, and baseline lesions (3-18; 19-70) and atopic dermatitis history (with AD history; without AD history) as covariates. An 
unstructured covariance matrix was used to model the within subject correlation. 
[2] P-value for testing difference (SB206 minus Vehicle Gel) in change from baseline is 0. 
SOURCE: Listing 16.2.6.1 
 
 
 
 
 
Programming Note: Update covariance structure and footnote as needed per the SAP text. 
 
 
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Table 14.2.1.6 
Percent Change from Baseline in Lesion Count by Study Visit and Treatment 
Summary of Fitted Summary Statistics from MMRM 
mITT Population 
Programming Note: Same shell as 14.2.1.5, update “change from baseline” text in body of table and footnote to “percent change from baseline” where applicable. Update ‘CFB’ to ‘% 
CFB’. 
 
 
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PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 51 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.2.1.7 
Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start of Dosing 
mITT Population 
 
 
 
SB206 
 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
n Censored (%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
P-value [1] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the number of subjects in the mITT population. N is the number of subjects in the mITT population. Subjects are 
summarized by randomized treatment. All estimates calculated using Kaplan-Meier product-limit survival curve methodology. Complete clearance is defined as a subject having a 
lesion count of 0. Time to complete clearance is calculated as complete clearance date – first application date + 1. 
[1] P-value from a log-rank test, comparing SB206 to Vehicle Gel. 
SOURCE: Listing 16.2.6.1, 16.2.6.2 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 52 of 98 
 
 
Figure 14.2.1.7 
Kaplan-Meier Plot of Time to Complete Clearance (Days) from Start of Dosing 
mITT Population 
Programming Note: x-axis will read “Days from Start of Dosing”, y-axis will read “Proportion of Subjects Yet to Achieve Complete Clearance”.  Curves for vehicle gel, individual active 
SB206 groups, and a pooled SB206 group will be presented.  Footnote will read “Note: Subjects are summarized by randomized treatment. Complete clearance is defined as a subject 
having a lesion count of 0. Time to complete clearance is calculated as complete clearance date – first application date + 1. SOURCE: Listing 16.2.6.1, 16.2.6.2 
 
 
Page 53


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 53 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.2.1.8 
Kaplan-Meier Estimates of Time to Sustained Complete Clearance (Days) from Start of Dosing 
mITT Population 
 
 
 
SB206 
 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
n Censored (%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
P-value [1] 
 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the number of subjects in the mITT population. N is the number of subjects in the mITT population. Subjects are 
summarized by randomized treatment. All estimates calculated using Kaplan-Meier product-limit survival curve methodology. Sustained complete clearance is defined as a 
subject having a lesion count of 0 and maintaining a count of 0 through Week 12. Time to sustained complete clearance is calculated as sustained complete clearance date – first 
application date + 1. 
[1] P-value from a log-rank test, comparing SB206 to Vehicle Gel. 
SOURCE: Listing 16.2.6.1, 16.2.6.2 
 
 
 
 
 
 
 
 
Page 54


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 54 of 98 
 
 
Figure 14.2.1.8 
Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start of Dosing 
mITT Population 
Programming Note: x-axis will read “Days from Start of Dosing”, y-axis will read “Proportion of Subjects Yet to Achieve Sustained Complete Clearance”.  Curves for vehicle gel, 
individual active SB206 groups, and a pooled SB206 group will be presented.  Footnote will read “Note: Subjects are summarized by randomized treatment. Sustained complete 
clearance is defined as a subject having a lesion count of 0 and maintaining a count of 0 through Week 12. Time to sustained complete clearance is calculated as sustained complete 
clearance date – first application date + 1. SOURCE: Listing 16.2.6.1, 16.2.6.2 
Page 55


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 55 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.2.1.9 
Summary of Increases and Decreases from Baseline in Lesion Count 
mITT Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
  Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 1 
 
 
 
 
 
 
   Increase from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No Change from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Decrease from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
   Increase from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No Change from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Decrease from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
   Increase from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No Change from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Decrease from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 8 
 
 
 
 
 
 
   Increase from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No Change from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Decrease from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
   Increase from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   No Change from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Decrease from Baseline 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the mITT population. The denominator for percentage corresponds to the number of subjects in the mITT population. Subjects are summarized 
by randomized treatment. Baseline is defined as the last measurement taken on or before the date of first application of study drug. 
SOURCE: Listing 16.2.6.1 
 
 
 
 
 
 
Page 56


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 56 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.2.1.10 
Summary of Subjects that Develop New Lesions after Achieving a Lesion Count of 0 
mITT Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
  Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
   Number of Subjects with a Previous Lesion Count of 0 
XX 
XX 
XX 
XX 
XX 
XX 
   Lesion Count >0 After Previous Lesion Count of 0 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
   Number of Subjects with a Previous Lesion Count of 0 
XX 
XX 
XX 
XX 
XX 
XX 
   Lesion Count >0 After Previous Lesion Count of 0 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 8 
 
 
 
 
 
 
   Number of Subjects with a Previous Lesion Count of 0 
XX 
XX 
XX 
XX 
XX 
XX 
   Lesion Count >0 After Previous Lesion Count of 0 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
   Number of Subjects with a Previous Lesion Count of 0 
XX 
XX 
XX 
XX 
XX 
XX 
   Lesion Count >0 After Previous Lesion Count of 0 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the mITT population. Subjects are summarized by randomized treatment. The denominator for percentage corresponds to the number of subjects 
with a lesion count of 0 at the previous visit. 
SOURCE: Listing 16.2.6.1 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 57 of 98 
 
 
Table 14.2.2.1 
Summary of Lesion Counts 
ITT Population 
 
Same shell as 14.2.1.1, update footnote to: “N is the number of subjects in the ITT population.” 
 
Figure 14.2.2.1.1 
Mean Change from Baseline in Lesion Count over Time by Treatment Group 
ITT Population 
 
Same shell as 14.2.1.1.1 
 
Figure 14.2.2.1.2 
Mean Percent Change from Baseline in Lesion Count over Time by Treatment Group 
ITT Population 
 
Same shell as 14.2.1.1.2 
 
Table 14.2.2.2 
Summary of Lesion Count Responders 
mITT Population 
 
Same shell as 14.2.1.2, update footnote to: “N is the number of subjects in the ITT population.” 
 
Table 14.2.2.3 
Complete Clearance Lesion Count Response by Study Visit and Treatment Group 
Summary of Fitted Point Estimates from Logistic Regression 
ITT Population  
Same shell as 14.2.1.3, update footnote to: “N is the number of subjects in the ITT population.” 
Table 14.2.2.4 
Proportion of Subjects with at Least a 75% Reduction in Lesion Count from Baseline Response by Study Visit and Treatment Group 
Tabulation of Fitted Point Estimates from Logistic Regression 
ITT Population 
 
Same shell as 14.2.1.4, update footnote to: “N is the number of subjects in the ITT population.” 
 
Table 14.2.2.5 
Change from Baseline in Lesion Count by Study Visit and Treatment 
Adjusted (Least Squares) Means from MMRM 
ITT Population 
 
Same shell as 14.2.1.5, update footnote to: “N is the number of subjects in the ITT population.” 
 
 
Page 58


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 58 of 98 
 
 
Table 14.2.2.6 
Percent Change from Baseline in Lesion Count by Study Visit and Treatment 
Summary of Fitted Summary Statistics from MMRM 
mITT Population 
 
Same shell as 14.2.1.6, update footnote to: “N is the number of subjects in the ITT population.” 
 
Table 14.2.2.7 
Kaplan-Meier Estimates of Time to First Complete Clearance (Days) from Start of Dosing 
ITT Population 
 
Same shell as 14.2.1.7, update footnote to: “The denominator for percentage corresponds to the number of subjects in the ITT population. N is the number of subjects in 
the ITT population.” 
 
Figure 14.2.2.7 
Kaplan-Meier Plot of Time to Complete Clearance (Days) from Start of Dosing 
ITT Population 
 
Same shell as 14.2.1.7 
 
Table 14.2.2.8 
Kaplan-Meier Estimates of Time to Sustained Complete Clearance (Days) from Start of Dosing 
mITT Population 
 
Same shell as 14.2.1.8, update footnote to: “The denominator for percentage corresponds to the number of subjects in the ITT population. N is the number of subjects in 
the ITT population.” 
 
Figure 14.2.2.8 
Kaplan-Meier Plot of Time to Sustained Complete Clearance (Days) from Start of Dosing 
ITT Population 
 
Same shell as 14.2.1.8 
 
Table 14.2.2.9 
Summary of Increases and Decreases from Baseline in Lesion Count 
ITT Population 
 
Same shell as 14.2.1.9, update footnote to: “The denominator for percentage corresponds to the number of subjects in the ITT population. N is the number of subjects in 
the ITT population.” 
 
Table 14.2.2.10 
Summary of Subjects that Develop New Lesions after Achieving a Lesion Count of 0 
ITT Population 
 
Same shell as 14.2.1.10, update footnote to: “N is the number of subjects in the ITT population.” 
Page 59


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 59 of 98 
 
 
 
Table 14.2.3.1 
Complete Clearance Lesion Count Response by Study Visit and Treatment Group 
Summary of Fitted Point Estimates from Logistic Regression 
PP Population  
Same shell as 14.2.1.3, update footnote to: “N is the number of subjects in the PP population.” 
 
 
Table 14.2.4.1 
Complete Clearance Lesion Count Response by Study Visit and Treatment Group 
Summary of Fitted Point Estimates from Logistic Regression 
Sensitivity Analysis Excluding Subjects from Same Household 
mITT Population  
Same shell as 14.2.1.3, add the following text to the footnote: “Subjects with at least one other subject from the same household enrolled in the study were excluded from the 
analysis.” 
 
 
 
Page 60


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 60 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events 
Safety Population 
 
 
 
SB206 
 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
Category 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
Subjects with a Related TEAE [1] 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
Subjects with an AE leading to Treatment Discontinuation 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
Subjects with an AE leading to Death 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
Subjects with at least one SAE 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: TEAE = Treatment emergent adverse event; SAE = Serious treatment emergent adverse event. 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Number of subjects experiencing an event, percentage of subjects experiencing an event, and total number of events are summarized. AEs were coded using MedDRA version 20.1. 
TEAEs are events that occurred or worsened on or after the first application of study drug. AEs with a missing severity were considered severe. 
[1] AEs with a relationship of definite, probable, possible, or missing were considered related. 
SOURCE: 16.2.7.1 
 
 
 
 
 
 
 
 
Page 61


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Novan, Inc. 
CONFIDENTIAL 
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<Version> 
Table 14.3.1.2 
Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
 
 
SB206 
System Organ Class 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Preferred Term 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
SOC 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   PT 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   PT 2 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   PT 3 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
SOC 2 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   PT 4 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   PT 5 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: TEAE = Treatment emergent adverse event. 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Number of subjects experiencing an event, percentage of subjects experiencing an event, and total number of events are summarized. AEs were coded using MedDRA version 20.1. 
TEAEs are events that occurred or worsened on or after the first application of study drug. Subjects are counted once for each system organ class (SOC) and once for each 
preferred term (PT). AEs are displayed alphabetically by SOC and PT. 
SOURCE: Listing 16.2.7.1 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.3.1.3 
Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Severity 
Safety Population 
 
System Organ Class 
 
SB206 
   Preferred Term 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
      Severity 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   Any Event (Total) 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Mild 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Moderate 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Severe  
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
SOC 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   Any Event (Total) 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Mild 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Moderate 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Severe  
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
   PT 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Mild 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Moderate 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Severe  
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
  PT 2 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Mild 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Moderate 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Severe  
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: TEAE = Treatment emergent adverse event. 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Number of subjects experiencing an event, percentage of subjects experiencing an event, and total number of events are summarized. AEs were coded using MedDRA version 20.1. 
TEAEs are events that occurred or worsened on or after the first application of study drug. Subjects are counted once for each system organ class (SOC) and once for each 
preferred term (PT). The severity shown is the greatest severity reported for a particular subject (Severe > Moderate > Mild). AEs with a missing severity were counted as severe. 
AEs are displayed alphabetically by SOC and PT. 
SOURCE: Listing 16.2.7.1 
 
 
 
 
 
 
 
 
 
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<Version> 
Table 14.3.1.4 
Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Relationship to Study Drug 
Safety Population 
 
System Organ Class 
 
SB206 
   Preferred Term 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
      Relationship 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   Any Event (Total) 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Not Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
SOC 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
   Any Event (Total) 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Not Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
   PT 1 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Not Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
  PT 2 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Not Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
 
 
 
 
 
 
   PT 3 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Not Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
      Related 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
XX (XX.X%) XX 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: TEAE = Treatment emergent adverse event. 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Number of subjects experiencing an event, percentage of subjects experiencing an event, and total number of events are summarized. AEs were coded using MedDRA version 20.1. 
TEAEs are events that occurred or worsened on or after the first application of study drug. Subjects are counted once for each system organ class (SOC) and once for each 
preferred term (PT). The relationship shown is the strongest relationship reported for a particular subject (Related > Not Related). AEs with a missing relationship were counted as 
related. AEs with a relationship of definite, probable, or possible were considered related. AEs with a relationship of unlikely or unrelated were considered not related. AEs are 
displayed alphabetically by SOC and PT. 
SOURCE: Listing 16.2.7.1 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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Table 14.3.1.5 
Summary of Serious Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Severity 
Safety Population 
Same shell as 14.3.1.3, update text in first row to: “Subjects with at least one SAE”. Add “SAE = Serious Treatment Emergent Adverse Event” to abbreviation footnote. 
 
Table 14.3.1.6 
Summary of Serious Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Relationship to Study Drug 
Safety Population  
Same shell as 14.3.1.4, update text in first row to: “Subjects with at least one SAE”. Add “SAE = Serious Treatment Emergent Adverse Event” to abbreviation footnote. 
 
 
Page 65


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
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<Version> 
Table 14.3.2.1 
Listing of Serious Adverse Events 
Safety Population 
 
Actual Treatment Received: SB206 4% BID 
 
System Organ Class/ 
 
 
Outcome/ 
 
 
   Preferred Term/ 
Start Date (Study Day)/ 
Severity/ 
   Study Drug Action Taken/ 
Serious?/ 
Subject ID 
      Verbatim Term 
   End Date (Study Day) 
   Relationship 
      Medical Treatment Received? 
   Criteria Met 
 
 
 
 
 
 
XXXXXXXXX 
XXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XXXXXXX/ 
XXXXX/ 
XXXXXXXX/ 
 
   XXXXXXXXX/ 
   DDMMMYYYY (XX) 
   XXXXXXXX 
    XXXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXX 
 
      XXXXXXXXXXXXXXX 
 
 
      XXX 
 
 
 
 
 
 
 
XXXXXXXXX 
XXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XXXXXXX/ 
XXXXX/ 
XXXXXXXX/ 
 
   XXXXXXXXX/ 
   DDMMMYYYY (XX) 
   XXXXXXXX 
    XXXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXX 
 
      XXXXXXXXXXXXXXX 
 
 
      XXX 
 
… 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: TEAE = Treatment emergent adverse event. 
Note: Study day is calculated relative to the date of first application of study drug. AEs were coded using MedDRA version 20.1. TEAEs are events that occurred or worsened 
on or after the first application of study drug. 
 
 
 
Page 66


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 66 of 98 
 
 
Table 14.3.2.2 
Listing of Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
Same shell as 14.3.2.1, only include AEs leading to study drug discontinuation. 
 
Table 14.3.2.3 
Listing of Adverse Events Leading to Death 
Safety Population 
Same shell as 14.3.2.1, only include AEs leading to death. 
 
 
Page 67


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Novan, Inc. 
CONFIDENTIAL 
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<Version> 
Table 14.3.5.1.1 
Summary of Serum Chemistry Laboratory Results 
Safety Population 
 
Analyte 
 
SB206 
  Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
    Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
XXXXXXXXXXX (units) 
 
 
 
 
 
 
  Baseline 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
  Week 1 Observed 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
  Week 1 Change from Baseline 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Std Dev 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
…Include all visits and analytes with data. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the safety population. Subjects are summarized by treatment received. Baseline is defined as the last measurement taken on or before the date 
of first application of study drug. 
SOURCE: Listing 16.2.8.1.1 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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<Version> 
Table 14.3.5.1.2 
Shift of Serum Chemistry Laboratory Results from Baseline 
Safety Population 
 
Analyte 
Baseline Value 
   Study Visit 
Vehicle Gel (N = XX) 
 
SB206 4% BID (N = XX) 
    Category 
Low 
Medium 
High 
Total 
 
Low 
Medium 
High 
Total 
 
 
 
 
 
 
 
 
 
 
Analyte 1 (units) 
 
 
 
 
 
 
 
 
 
  Week 1 
 
 
 
 
 
 
 
 
 
    Low 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Medium 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    High 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Total 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
 
 
 
 
 
 
 
 
 
  Week 2 
 
 
 
 
 
 
 
 
 
    Low 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Medium 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    High 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Total 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
 
 
 
 
 
 
 
 
 
  Week 4 
 
 
 
 
 
 
 
 
 
    Low 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Medium 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    High 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Total 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
 
 
 
 
 
 
 
 
 
…Continue for other analytes and visit. Once all analytes have been summarized for first two treatments, begin summary for next two treatments on a new 
page. Repeat until all treatments, including SB206 Overall group have been summarized. Only summarize visits and analytes with non-missing values 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the number of subjects with a non-missing baseline value and a non-missing value at a visit. N is the number of 
subjects in the safety population. Subjects are summarized by treatment received. Baseline is defined as the last measurement taken on or before the date of first 
application of study drug. 
SOURCE: Listing 16.2.8.1.1 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 69 of 98 
 
 
Table 14.3.5.2.1 
Summary of Hematology Laboratory Results 
Safety Population 
Same shell as 14.3.5.1.1. change source listing to 16.2.8.1.2 
 
Table 14.3.5.2.2 
Shift of Hematology Laboratory Results from Baseline 
Safety Population 
Same shell as 14.3.5.1.2, change source listing to 16.2.8.1.2 
 
Table 14.3.5.3 
Summary of Methemoglobin Results 
Safety Population 
Same shell as 14.3.5.1.1, visits will include Baseline, Week 1, Week 2, Week 4, Week 8 , and Week 12. Change source listing to 16.2.8.1.3 
 
Table 14.3.6.1 
Summary of Vital Signs Results 
Safety Population 
Same shell as 14.3.5.1.1, change “Analyte” text in header to “Parameter”. Include supine blood pressure (mmHg), diastolic blood pressure (mmHg), and heart rate 
(beats/min).  Visits will include Baseline and Week 12 Change source listing to 16.2.8.3 
 
 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
PCN Number NOVT177332 
 
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Protocol NI-MC201 
 
<Version> 
Table 14.3.6.2 
Summary of Local Tolerability Results 
Safety Population 
 
Study Visit 
Vehicle Gel 
 
SB206 
   Parameter 
BID 
QD 
Overall 
 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
     Category 
(N = XX) 
(N = XX) 
(N = XX) 
 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   Investigator assessment of dryness, erythema, 
and peeling 
 
 
 
 
 
 
 
 
 
      0 = No irritation 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      1 = Mild 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      2 = Moderate 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      3 = Severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      4 = Very severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
   Subject assessment of burning/stinging and itching 
 
 
 
 
 
 
 
 
 
      0 = None 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      1 = Slight 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      2 = Mild 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      3 = Moderate 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
      4 = Strong/Severe 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Continue for Week 1, Week 2, Week 4, Week 8, and Week 12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the N in each column. N is the number of subjects in the safety population. Subjects are summarized by treatment received. Baseline 
is defined as the last measurement taken on or before the date of first application of study drug. 
SOURCE: Listing 16.2.8.4 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
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Protocol NI-MC201  
 
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<Version> 
Table 14.3.6.3 
Shift of Local Tolerability Results  
Safety Population 
 
Assessment 
Baseline Value 
  Study Visit 
Vehicle Gel BID (N = XX) 
    Category 
0 = None 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Very Severe 
Total 
 
 
 
 
 
 
 
Investigator 
 
 
 
 
 
 
  Week 1 
 
 
 
 
 
 
    0 = None 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    1 = Mild 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    2 = Moderate 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    3 = Severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    4 = Very severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Total 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Week 2  
 
 
 
 
 
 
    0 = None 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    1 = Mild 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    2 = Moderate 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    3 = Severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    4 = Very severe (AE) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
    Total 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX 
 
 
 
 
 
 
 
Continue for Week 4, Week 8, and Week 12, repeat for Subject assessment (update category rows to: 0 = None, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Strong/Severe). Once 
both assessments have been summarized for first treatment, begin summary for next treatment on a new page. Repeat until all treatments, including Vehicle Gel QD, Vehicle 
Gel Overall, SB206 dose levels, and SB206 Overall group have been summarized. Subject assessment should start on a new page and the header categories should be 
updated accordingly. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the N within each treatment. N is the number of subjects in the safety population. Subjects are summarized by treatment received. 
Baseline is defined as the last measurement taken on or before the date of first application of study drug. 
SOURCE: Listing 16.2.8.4 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
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<Version> 
Table 14.3.6.4 
Summary of Concomitant Medications 
Safety Population 
 
 
 
SB206 
Anatomic Therapeutic Chemical Classification 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
   Preferred Term 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Subjects with at least one Prior Medication 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
ATC 1 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 1 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 2 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 3 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 4 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 5 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 6 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
ATC 2 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 7 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 8 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
   Preferred Term 9 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
XX (XX.X%) 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The denominator for percentage corresponds to the number of subjects in the safety population. N is the number of subjects in the safety population. Subjects are 
summarized by treatment received. Medications coded using WHO-DDE version 01SEP2017. Concomitant medications are all medications with a start date on or after the first 
application of study drug, or those with a start date before the first application of study drug that were ongoing or with a stop date on or after the first application of study drug. If 
medication dates are incomplete and it was not clear whether the medication was concomitant, it was assumed to be concomitant. Medications are displayed alphabetically by 
Anatomic Therapeutic Class (ATC) and then by Preferred Term (PT). Subjects are counted once for each ATC and PT. 
SOURCE: Listing 16.2.8.6 
 
 
 
Page 73


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 73 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Table 14.4.1 
Summary of hMAP3 Plasma Concentrations 
Exposure Population 
 
 
 
SB206 
Study Visit 
Vehicle Gel 
4% BID 
X% XXX 
X% XXX 
X% XXX 
Overall 
  Statistic 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
(N = XX) 
 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
   n 
0 
0 
0 
XX 
XX 
XX 
   Mean 
 
 
 
XX.X 
XX.X 
XX.X 
   Geometric Mean 
 
 
 
XX.X 
XX.X 
XX.X 
   Std Dev 
 
 
 
XX.XX 
XX.XX 
XX.XX 
   Median 
 
 
 
XX.X 
XX.X 
XX.X 
   Min, Max 
 
 
 
XX, XX 
XX, XX 
XX, XX 
   % CV 
 
 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N is the number of subjects in the exposure population. Subjects are summarized by treatment received. 
SOURCE: Listing 16.2.5.3 
 
 
 
 
 
 
 
Page 74


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 74 of 98 
 
 
Planned Listing Shells 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.1.1 
Subject Disposition 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
Date of Study 
 
 
 
If Lost to Follow-up 
 
 
 
 
 
Discontinuation 
Date of 
Reason for Drug 
Reason for Study 
Date of 
 
 
Subject Blind 
 Subject ID 
or Completion 
Last Application 
Discontinuation 
Discontinuation 
Last Contact 
Last Visit 
 
Broken? 
Date 
Reason 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
Completed 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
XXXXXXXXXXXXXXXXXXX 
Withdrawal by 
subject/caregiver 
 
 
 
Yes 
DDMMMYYYY 
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
Completed 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
Completed 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
Completed 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: If reason for discontinuation is AE, physician decision, protocol violation, or other, concatenate reason with “: specify text”. 
Page 75


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 75 of 98 
 
 
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CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.1.2 
Inclusion and Exclusion Criteria 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
Date of 
All Inclusion 
Inclusion Criteria 
Any Exclusion 
Exclusion Criteria 
 Subject ID 
Screening 
Criteria Met? 
Not Met 
Criteria Met? 
Met 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 76


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 76 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
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Protocol NI-MC201 
 
<Version> 
Listing 16.2.1.3 
Subject Randomization 
 
 
 
Randomization 
Randomization 
 
Randomized 
Actual 
 Subject ID 
Date 
ID 
Cohort 
Treatment 
Treatment 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
XXXX 
Cohort X 
XXXXXXXXXX 
XXXXXXXXXXXX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
XXXX 
Cohort X 
XXXXXXXXXX 
XXXXXXXXXXXX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
XXXX 
Cohort X 
XXXXXXXXXX 
XXXXXXXXXXXX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
XXXX 
Cohort X 
XXXXXXXXXX 
XXXXXXXXXXXX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
XXXX 
Cohort X 
XXXXXXXXXX 
XXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 77


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 77 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.2 
Protocol Deviations 
 
Format TBD once final protocol deviation list is received. 
 
 
 
Page 78


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 78 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.3 
Analysis Populations 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
Analysis Population 
 
 Subject ID 
Safety 
mITT 
ITT 
Exposure 
PP 
Primary Reason for Exclusion 
 
 
 
 
 
 
 
XXXXXX 
Yes 
Yes 
Yes 
No 
Yes 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
XXXXXX 
Yes 
No 
Yes 
No 
Yes 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
XXXXXX 
Yes 
Yes 
Yes 
No 
Yes 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
XXXXXX 
Yes 
Yes 
Yes 
No 
Yes 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
XXXXXX 
Yes 
Yes 
Yes 
No 
No 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 79


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 79 of 98 
 
 
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CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.4.1 
Demographics and Baseline Characteristics 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
Date of 
Date of Informed 
Consent/ 
Age 
 
 
 
Family 
Members 
Randomized 
(IWRS)/Actual 
Start Date of 
Current 
 Subject ID 
Birth 
   Assent 
 (years) 
Gender 
Ethnicity 
Race 
Randomized 
AD Group  
Molluscum 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY/ 
   DDMMMYYYY 
XX 
(XXXX) 
F 
XXXXXXXXXXXXX 
XXXXXXXXXXX 
No 
AD/AD 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY/ 
   DDMMMYYYY 
XX 
(XXXX) 
F 
XXXXXXXXXXXXX 
XXXXXXXXXXX 
No 
No AD/AD 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY/ 
   DDMMMYYYY 
XX 
(XXXX) 
F 
XXXXXXXXXXXXX 
XXXXXXXXXXX 
No 
AD/AD 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY/ 
   DDMMMYYYY 
XX 
(XXXX) 
F 
XXXXXXXXXXXXX 
XXXXXXXXXXX 
No 
No AD/No AD 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY/ 
   DDMMMYYYY 
XX 
(XXXX) 
F 
XXXXXXXXXXXXX 
XXXXXXXXXXX 
XXXXXX 
AD/AD 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: AD = Atopic dermatitis 
Note: Randomized AD group is the stratification group subjects were assigned to by the site prior to randomization. Actual AD group is whether or not subjects actually have AD history. 
 
Programming Note: If multiple races are selected, concatenate the values separating with a semi-colon. If “Other” race is selected, concatenate with specify text – “Other: specify 
text”. If no family memebers have been randomized, list “No”. If at least one family member has been randomized, list subject numbers. 
 
 
 
Page 80


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 80 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.4.2 
Medical History 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
System Organ Class/ 
 
 
   Preferred Term/ 
Start Date/ 
 Subject ID 
      Verbatim Term 
   End Date 
 
 
 
XXXXXX 
XXXXXXXXXXXXXXXXXXX/ 
DDMMYYYY/ 
 
  XXXXXXXXXXXXXXXXX/ 
  DDMMYYYY 
 
    XXXXXXXXXXXXXXXX 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXX/ 
DDMMYYYY/ 
 
  XXXXXXXXXXXXXXXXX/ 
  DDMMYYYY 
 
    XXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
Note: Medical history was coded using MedDRA version 20.1. 
 
 
 
Page 81


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 81 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.5.1 
Study Drug Administration 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
Study Drug 
Date/Time of 
 Subject ID 
Study Visit 
Administered? 
Administration 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM 
 
 
 
 
 
 
 
 
 
 
 
Page 82


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.5.2 
Study Drug Accountability 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
 
 
 
Drug Dispensed 
Dispensation 
Kit ID 
Weight of Blue 
Weigh of Yellow 
Number of 
 
 
Dispensed 
or Returned 
or Return 
Dispensed 
Tubes Dispensed 
Tubes Dispensed 
Doses Missed 
 Subject ID 
Study Visit 
or Returned? 
at Visit? 
Date 
or Returned 
or Returned (Units) 
or Returned (Units) 
Since Last Visit 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
 
 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
 
 
XXXXXXXXXXXXX 
Dispensed 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
 
 
XXXXXXXXXXXXX 
Returned 
Yes 
DDMMYYYY 
XXXX 
XX (XX) 
XX (XX) 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 83


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 83 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.5.3 
Pharmacokinetic Blood Concentration 
 
 
Randomized Treatment: Cohort 3, SB206 XXXXXX 
 
 
PK Sample 
Date of Assesment 
hMAP3 Concentration 
 Subject ID 
Study Visit 
Collected? 
(Study Day) 
(units) 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX.X 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
 
Page 84


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 84 of 98 
 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.6.1 
Lesion Counts 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
 
Rater 
Assessment 
Assessment Date 
Total Number 
Complete 
% Reduction 
 Subject ID 
Study Visit 
Initial 
Performed? 
(Study Day) 
of Lesions 
Clearance? 
from Baseline 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
 
No 
DDMMYYYY (XX) 
 
 
 
 
XXXXXXXXXXXXX* 
XX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
XXXXXXXXXXXXX 
XXX 
Yes 
DDMMYYYY (XX) 
XX 
No 
10.2% 
 
XXXXXXXXXXXXX 
XXX 
Yes 
DDMMYYYY (XX) 
XX 
No 
XX% 
 
XXXXXXXXXXXXX 
XXX 
Yes 
DDMMYYYY (XX) 
XX 
No 
XX% 
 
XXXXXXXXXXXXX 
XXX 
Yes 
DDMMYYYY (XX) 
XX 
Yes 
XX% 
 
XXXXXXXXXXXXX 
XXX 
Yes 
DDMMYYYY (XX) 
XX 
Yes 
XX% 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
 
No 
DDMMYYYY (XX) 
 
 
 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
XX 
XX.X% 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
XX 
XX.X% 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
XX 
XX.X% 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
XX 
XX.X% 
 
XXXXXXXXXXXXX 
XX 
Yes 
DDMMYYYY (XX) 
XX 
XX 
XX.X% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. Complete clearance is defined as a subject having a lesion count of 0 at a visit. Visits marked 
with ‘*’ are baseline. Baseline is defined as the last measurement taken on or before the date of first application of study drug. 
 
 
 
Page 85


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
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Protocol NI-MC201 
 
<Version> 
Listing 16.2.6.2 
Lesion Count Derived Efficacy Variables, Time to Complete Clearance and 75% Reduction from Baseline 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
Date of First Application of 
 
Clearance 
Date Achieved or 
Days After 
 Subject ID 
Study Drug 
Variable 
Achieved? 
Censoring Date 
First Application 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Complete Clearance 
No 
DDMMMYYYY 
XX 
 
 
75% Clearance 
Yes 
DDMMMYYYY 
XX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Complete Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
75% Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Complete Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
75% Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY 
Complete Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
75% Clearance 
XXX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Note; Days after first application is calculated as date of achievement or censoring – date of first application + 1. 
Page 86


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 86 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.7.1 
Adverse Events 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
System Organ Class/ 
 
 
 
 
 
Any Adverse 
   Preferred Term/ 
Start Date (Study Day)/ 
Severity/ 
Outcome/ 
Serious?/ 
 Subject ID 
Events Reported? 
      Verbatim Term 
   End Date (Study Day) [1] 
   Relationship 
   Action Taken with Study Treatment 
   Criteria Met 
 
 
 
 
 
 
 
XXXXXX 
Yes 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XXXXXXXXXX/ 
XXXXXXXXX/ 
XX/ 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
   XXXXXXXXXXXX 
   XXXXXXXXXXXXXX 
   XXXXXXXXXXXX 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XXXXXXXXXX/ 
XXXXXXXXX/ 
XX/ 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
   XXXXXXXXXXXX 
   XXXXXXXXXXXXXX 
   XXXXXXXXXXXX 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XXXXXXXXXX/ 
XXXXXXXXX/ 
XX/ 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
   XXXXXXXXXXXX 
   XXXXXXXXXXXXXX 
   XXXXXXXXXXXX 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. AEs were coded using MedDRA version 20.1. 
 
Programming Note: If multiple SAE criteria are met, concatenate each criteria. 
 
 
Page 87


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 87 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.1.1 
Serum Chemistry Laboratory Results 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
Sample 
Date of Assesment 
Standard 
Standard 
Reference Range [1] 
 Subject ID 
Laboratory Test 
Study Visit 
Collected? 
(Study Day) 
Results 
Units 
Low 
High 
Flag 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
L 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
H 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: H = High; L = Low; A = Abnormal. 
Note: Study day is calculated relative to the date of the first application of study drug. 
[1] Reference range is used to identify potentially clinically significant laboratory values. 
 
 
 
Page 88


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 88 of 98 
 
 
Listing 16.2.8.1.2 
Hematology Laboratory Results 
 
Same shell as 16.2.8.1.1 
 
 
 
 
Page 89


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 89 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.1.3 
Methemoglobin Results 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
Methemoglobin 
Assessment Date 
Methemoglobin 
 Subject ID 
Study Visit 
Collected? 
(Study Day) 
Result (g/dL) 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
Page 90


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 90 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.2 
Pregnancy Test 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
Pregnancy Test 
Assessment Date 
Pregnancy Test 
 Subject ID 
Study Visit 
Performed? 
(Study Day) 
Results 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMYYYY (XX) 
XX 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
Page 91


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 91 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.3 
Vital Signs Results 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
Vital Signs 
Date of Assesment 
Height 
Weight 
Body Mass 
Heart Rate 
Systolic Blood 
Diastolic Blood 
 Subject ID 
Study Visit 
Collected? 
(Study Day) 
(units) 
(units) 
Index (kg/m2) 
(bpm) 
Pressure (mmHg) 
Pressure (mmHg) 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX (XX) 
XX (XX) 
XX 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XX (XX) 
XX (XX) 
XX 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
 
Page 92


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 92 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.4 
Local Tolerability Assessment 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 Local Tolerability 
 Date/Time of Assessment 
Investigator Assessment 
Subject Assessment 
 Subject ID 
Study Visit 
Collected? 
(Study Day) 
of Dryness, Erythema, and Peeling [1] 
of Burning/Stinging and Itching [2] 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM (XX) 
0 = No irritation 
0 = None 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
1 = Mild 
1 = Slight 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
2 = Moderate 
2 = Mild 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
3 = Severe 
3 = Moderate 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
4 = Very Severe 
4 = Strong/Severe 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY:HH:MM (XX) 
X = XXXXXX 
X = XXXXXX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
X = XXXXXX 
X = XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
[1] 0 = No irritation indicates ‘No evidence of local irritation/intolerance’; 1 = Mild indicates ‘Minimal erythema and/or edema, slight glazed appearance’; 2 = Moderate indicates ‘Definite 
erythema and/or edema with peeling and/or cracking but does not require treatment modification’; 3 = Severe indicates ‘Erythema, edema glazing with fissures, few vesicles or papules’; 
4 = Very Severe indicates ‘Strong reaction spreading beyond the treated area, bullous reaction, erosions’. 
[2] 0 = None indicates ‘Normal, no discomfort’; 1 = Slight indicates ‘An awareness, but no discomfort and no intervention required’; 2 = Mild indicates ‘A noticeable discomfort that causes 
intermittent awareness’; 3 = Moderate indicates ‘A noticeable discomfort that causes intermittent awareness and interferes occasionally with normal daily activities’; 4 = Strong/Severe 
indicates ‘A definite continuous discomfort that interferes with normal daily activities’. 
 
 
 
Page 93


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 93 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.5 
Physical Examination 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
Physical Examination 
 Date of Assessment 
Body 
 
 
Clinically 
 Subject ID 
Study Visit 
Performed? 
(Study Day) 
System 
Result 
Abnormal Findings 
Significant? 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
ABNORMAL 
XXXXXXXXXXXXXX 
No 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXX 
NORMAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. 
 
 
Page 94


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 94 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.6 
Concomitant Medications 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
 
 
 
Anatomic Therapeutic Class/ 
 
 
 
 
 
Any Medications 
 
   Preferred Term/ 
Start Date (Study Day)/ 
 
Route/ 
 
 Subject ID 
Reported? 
Concomitant? [1] 
      Verbatim Term 
   End Date (Study Day) [1] 
Dose (unit) 
   Frequency 
Reason for use/indication 
 
 
 
 
 
 
 
 
XXXXXX 
Yes 
Yes 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XX (XXX) 
XXX/ 
XXXXXX 
 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
 
   XX 
 
 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XX (XXX) 
XXX/ 
XXXXXX 
 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
 
   XX 
 
 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes 
XXXXXXXXXXXXX/ 
DDMMMYYYY (XX)/ 
XX (XXX) 
XXX/ 
XXXXXX 
 
 
 
   XXXXXXXXXXX/ 
   DDMMMYYYY (XX) 
 
   XX 
 
 
 
 
      XXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. Medications were coded using WHO-DD version DDMMMYYYY. 
[1] Concomitant indicates medication that started during the treatment period or started prior to first application of study drug and continued during the treatment period. 
 
 
 
Page 95


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 95 of 98 
 
 
Novan, Inc. 
CONFIDENTIAL 
Page x of y 
Protocol NI-MC201 
 
<Version> 
Listing 16.2.8.7 
Photography 
 
 
Randomized Treatment: Cohort 1, Vehicle Gel 4% BID 
 
 
Was Photography 
Collection 
 Subject ID 
Study Visit 
Collected? 
Date 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
 
XXXXXX 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
XXXXXXXXXXXXX 
Yes 
DDMMMYYYY (XX) 
 
 
 
 
 
 
 
 
Note: Study day is calculated relative to the date of the first application of study drug. Photography is only 
obtained for select sites and subjects. 
Page 96


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 96 of 98 
 
 
Appendix 1: Premier Research Library of Abbreviations 
Abbreviation 
Definition 
AD 
atopic dermatitis 
AE 
adverse event 
BID 
twice daily 
ATC 
anatomical therapeutic class 
BMI 
body mass index 
CRF 
case report form 
CEC 
central ethics committee 
CS 
clinically significant 
CSR 
clinical study report 
DOB 
date of birth 
DS 
document specialist 
DSG 
drug safety group 
DSM 
drug supply management (drug distributor) 
DSMB  
data safety monitoring board 
EC 
ethics committee 
EMA 
European medicines agency 
ET 
early termination 
FDA 
food and drug administration 
IC 
informed consent 
Page 97


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 97 of 98 
 
 
Abbreviation 
Definition 
ICH 
international council for harmonization  
mITT 
modified intent-to-treat 
ITT 
intent-to-treat 
LLOQ 
lower limit of quantification 
MedDRA 
medical dictionary for regulatory activities 
MC 
Molluscum Contagiosum 
MMRM 
mixed effect model repeat measurement 
NCS 
non-clinically significant 
NF 
non-functional 
NOVAN 
Novan, Inc. 
PD 
protocol deviation 
PE 
physical examination 
PP 
per-protocol 
QD 
once daily 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS®  
a software system used for data analysis 
SBP 
systolic blood pressure 
SC 
study coordinator 
SCR 
software change request  
Page 98


 
Statistical Analysis Plan,  
 
Novan, Inc.  
 
Protocol NI-MC201  
 
PCN Number NOVT177332 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version 1.0   |   17-AUG-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 98 of 98 
 
 
Abbreviation 
Definition 
SD 
standard deviation 
SDS 
study design specifications 
SDTM  
study data tabulation model  
SI 
International System of Units 
SOC 
system organ class 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TIW 
three times a week 
UPT 
urine pregnancy test 
WHO 
world health organization 
WHO-DD 
world health organization drug dictionary 
 
Page 99

Prot_001.pdf: 
16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscum Contagiosum Ascending Dose Study 
SB206/NVN1000 
DRUG: 
SB206/NVN1000 
STUDY NUMBER(S): 
NI-MC201 
PROTOCOL(S) TITLE: 
A PHASE 2 MULTI-CENTER, RANDOMIZED, 
DOUBLE-BLIND, VEHICLE-CONTROLLED, 
ASCENDING DOSE STUDY OF SB206 IN 
SUBJECTS WITH MOLLUSCUM CONTAGIOSUM 
IND NUMBER: 
137015 
SPONSOR: 
Novan, Inc 
ORIGINAL PROTOCOL DATE: 
10 November 2017 
VERSION NUMBER: 
Version 3.0 
AMENDMENT VERSION DATE: 
29 June 2018 


16.1.1 Protocol NI-MC201, Amendment 2 
Novan: A Phase 2 Molluscurn Contagiosurn Ascending Dose Study 
SB206!NVN1000 
CLINICAL PROTOCOL APPROVAL FORM 
Protocol Title: A PHASE 2 MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, VEIDCLE-
CONTROLLED, ASCENDING DOSE STUDY OF SB206 IN SUBJECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Study No: NI-MC201 
Original Protocol Date: 10 November 2017 
Protocol Version No: 3.0 
Protocol Amendment Version Date: 29 June 2018 
This study protocol was subject to critical review and has been approved by the appropriate 
protocol review committee of Novan. The information contained in this protocol is consistent 
with: 
• 
The current risk-benefit evaluation of the investigational product. 
• 
The moral, ethical and scientific principles goveming clinical research a'> set out in the 
Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 54, 56 
and 312 and according to applicable local requirements. 
The Investigator will be supplied with details of any significant or new findings, including 
adverse events, relating to treatment with the investigational product. 
Name and Title 
Author: 
Teresa Reams, Clinical Study Manager 
Clinical Operations: 
Emily de Leon, Director of Clinical 
Development 
Biometrics: 
Todd Durham, Head of Biostatistics 
Medical Lead: 
Tomoko Maeda-Chubachi, VP, Medical 
Dermatology 
Regulatory Affairs: 
Kevin Barber, VP, Regulatory Affairs 
Quality Assurance: 
Liz Troll, Head of Clinical Quality 
Assurance 
Approval 
No 
one) 
No 
No 
(circle one) 
Yes 
No 
(circle one) 
No 
(circle one) 
Yes 
No 
(circle one) 
Signature 
Date 
.:J..v.._._. L-
{IQ_c..,~ 
{~ · 
.2.t>i J (,lt\ ) 0 . 
j-vvt-?-~ 
~ l J1,..l-1 
l." I ~ 
~a 
ltf Ju).) 
·-io 16"' 


16.1.1 Protocol Nl-MC20 I, Amendment 2 
Novan: 1\ Phase 2 Molluscurn Contagiosurn Ascending Dose Study 
SB206/NVN 1000 
CLINICAL PROTOCOL APPROVAL FORM 
Protocol Title: A PHASE 2 MUL Tl-CENTER, RANDOMIZED, DOUBLE-BLIND, VEHICLE-
CONTROLLED, ASCENOING DOSE STUDY OF SR206 IN SUR.IECTS WITH MOLLUSCUM 
CONTAGIOSUM 
Study No: Nl-MC20t 
Original Protocol Date: lO November 2017 
Protocol Version No: 3.0 
Protocol Amendment Version Date: 29 June 2018 
This study protocol was subject to critical review and has been approved by the appropriate 
protocol review committee of Novan. The information contained in this protocol is consistent 
with: 
• 
The current risk-benefit evaluation of the investigational product. 
• 
The moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki, and principles of GCP as described in 21 CFR parts 50, 54, 56 
and 312 and according to applicable local requirements. 
The Investigator will be supplied with details of any significant or new findings, including 
adverse events. relating to treatment with the investigational product. 
-
Name and Title 
Approval 
Signature 
Date 
--
----
-
-
-
Author: 
Yes 
No 
Teresa Reams, Clinical Study Manager 
(circle one) 
-
--
--
--
-
~ 
-
Clinical Operations: 
Yes 
No 
Emily de Leon. Director of Clinical 
(circle one) 
Development 
---
-
>-- ·-
Biometrics: 
Yes 
No 
Todd Durham, Head of Biostatistics 
(circle one) 
-
-
Medical Lead: 
(:!_cJ 
No 
611/ 
Tomoko Maeda-Chubachi, VP, Medical 
-7/l 
/L--t.,~ 
Dermatology 
(circle one) 
__,,,.= 
I 
-
Regulatory Affairs: 
Yes 
No 
Kevin Barber, VP, Regulatory Atfairs 
(circle one) 
Quality Assurance: 
Yes 
No 
Liz Troll, Head of Clinical Quality 
(circle one) 
Assurance 
--


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


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


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


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


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


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


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


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


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


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


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


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


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


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• Adverse Events 
Exposure Endpoint 
• Determination of hMAP3 plasma concentration at end of treatment, if 
quantifiable 
 
STUDY SCHEMATIC 
 
*Note: T or NT is decided on a cohort basis, not on a subject level, after 30 subjects have 
completed 2 weeks of treatment.  
 
 
 


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


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


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


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


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


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


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1 INTRODUCTION AND RATIONALE 
1.1 
Background 
Molluscum contagiosum (MC) is a common skin disorder that aﬀects mainly healthy children 
(Dohil et al, 2006). MC has the greatest incidence in individuals aged 1–14 years (Schofield et al, 
2011); prevalence in children is between 5% and 11% (Olsen et al, 2014).  
MC virus is an important human skin pathogen and can cause disﬁgurement and suffering in 
children.  In adults MC is less common and often sexually transmitted. Extensive and persistent 
skin infection with the virus can indicate underlying immunodeﬁciency. MC virus is distinct from 
other poxviruses because of its host and tissue adaptations. It infects only the skin and, rarely, the 
mucous membranes. The virus has developed efficient mechanisms to grow in differentiating 
cells of the human epidermis and is well adapted to human hosts (Chen et al, 2013).  
Extensive and persistent skin infection with the virus can indicate underlying immunodeficiency. 
Patients with atopic dermatitis have an impaired skin barrier in addition to immunological changes 
which could explain the rising prevalence and high number of lesions in this population. Topical 
corticosteroids and calcineurin inhibitors (both local immunosuppressants commonly applied to 
the skin in patients with atopic dermatitis) have been implicated as contributing factors in some 
patients (Osio et al, 2011). 
MC is transmitted between human hosts by the infectious matter discharged from the lesions. 
According to a prospective community cohort study (Olsen et al, 2015), the mean time to 
resolution was 13.3 months (SD 8.2). Eighty (30%) of 269 cases had not resolved by 18 months; 
36 (13%) had not resolved by 24 months. Transmission to other children in the household occur 
in 102 (41%) of 250 cases.  
Acidified nitrite was used in a double-blind, group-sequential clinical trial to demonstrate the 
efficacy of nitric oxide donor in treating MC (Ormerod et al, 1999). In the study, subjects 
received either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical 
cream with 5% salicylic acid, omitting sodium nitrite. Completion was defined as 3 months, 
or when the patient was cured or dropped out, if sooner. The study demonstrated that a 75% 
cure rate in the active treatment group and 21% cure with control treatment (P = 0.01). The mean 
time to cure was 1.83 months. Staining of the skin and irritation were frequent side-effects 
but did not prevent successful treatment. 
Novan, Inc. (Novan) is conducting this Phase 2 multi-center, randomized, double-blind, vehicle-
controlled, ascending dose study of SB206 in subjects 2 years of age and older with molluscum 
contagiosum. SB206 is a topical gel, formed by mixing NVN1000 Gel with hydrogel. NVN1000 
Gel contains NVN1000, a nitric oxide-releasing macromolecule containing covalently bound N-
diazeniumdiolate nitric oxide donors; nitric oxide release from the macromolecule is initiated by 
mixing NVN1000 Gel with hydrogel. 
Topical formulations of NVN1000 at concentrations ranging from 1-16% have been studied in 19 
completed studies. Over 1900 healthy volunteers or subjects with acne, genital warts or tinea pedis 


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have been exposed to Vehicle and 2600 exposed to NVN1000. In clinical studies completed to 
date, topical application of NVN1000 has generally been well-tolerated with no safety concerns 
identified. A clinical study involving subjects with psoriasis just completed and one in subjects 
with atopic dermatitis is ongoing.  
1.1.1 
Pharmacokinetics 
The systemic bioavailability of NVN1000 after dermal administration has been investigated in two 
maximum use studies in adults and adolescent subjects with moderate to severe acne vulgaris, and 
no detectable systemic exposure was observed. In adult subjects with moderate to severe acne 
vulgaris (NI-AC101) administration of SB204 8% (NVN1000 Gel 16% co-administered with 
hydrogel) or Vehicle Gel daily for 5 days to the face, chest, back, upper shoulders twice daily 
(BID) (17% BSA) showed no detectable systemic exposure on Day 1 or Day 5 to hMAP3, a silicon 
containing component of the parent compound.  There was no noticeable difference in systemic 
nitrate levels on Day 1 or Day 5 in subjects treated with SB204 or Vehicle Gel and no evidence of 
accumulation. Likewise, in an open-label PK, study (NI-AC103) in adolescents (ages 9-16 years) 
with moderate to severe acne vulgaris topical administration of SB204 4% was applied QD for 
21 days to 17% BSA and again no detectable systemic exposure to hMAP3 and no plasma nitrate 
concentrations outside of normal variability and negligible accumulation of nitrate after 21 days 
of dosing.  
Additionally, in a 4-way, randomized, double-blind, cross-over study examining ECG effects 
following SB204 application (NI-AC104), there was no detectable systemic exposure to hMAP3 
and no difference in plasma nitrate levels in 48 subjects with moderate to severe acne treated with 
SB204 (NVN1000) Gel 4%, SB204 (NVN1000) Gel 12% or Vehicle Gel applied to 17% BSA.  
No changes in ECG were observed with therapeutic or supratherapeutic doses of SB204. 
In the recently completed study in subjects with psoriasis (NI-PS101) who were administered a 
cream formulation, SB414 6% (NVN1000 Ointment 12% co-administered with hydrogel),  6 of 
23 subjects (26.0%) had at least one quantifiable hMAP3 plasma concentration following dosing. 
The mean (SD) Cmax of hMAP3 (18.89 [15.02] ng/mL) occurred at 1 hour postdose in the 6 
subjects with quantifiable hMAP3 plasma concentrations. The plasma concentration gradually 
decreased after the peak and hMAP3 was below the the lower limit of quantitation (LLOQ)  in all 
subjects at 12 hours postdose. Systemic exposure to the investigational product was negligible in 
the study. The clinical study report is under preparation. Analyses are currently ongoing to 
determine systemic exposure in a study of subjects with atopic dermatitis (NI-AD101) 
administered SB414 2% (NVN1000 Ointment 4% co-administered with buffered hydrogel) or 6% 
(NVN1000 Ointment 12% co-administed with buffered hydrogel).  
1.1.2 
Preclinical Pharmacology 
During the development of SB204 (NVN1000 Gel) for acne, SB206 (NVN1000 Gel) for the 
treatment of external genital warts and perianal warts, SB208 (NVN1000 Gel) for tinea pedis and 
SB414 (NVN1000 Ointment), Novan has conducted over 90 nonclinical studies. With SB206, 
Novan completed a 4-week daily dosing with 2-week recovery GLP dermal bridging study in 
miniature swine. Under the conditions of this study, the No Observed Adverse Effect Level 


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


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methemoglobin in blood has been measured using pulse co-oximetry in the Phase 1 and Phase 2 
studies in the acne, external genital wart, and anti-fungal programs.  There have been no reports 
of methemoglobinemia or observed methemoglobin levels greater than 3% in subjects treated with 
topical NVN1000 in completed studies. Fluctuations in methemoglobin during treatment have 
been similar in subjects treated with topical NVN1000 or Vehicle.  There have been no clinically 
significant changes in physical examination, including vital signs, in subjects treated with topical 
NVN1000. 
1.1.5 
Elevations in Liver Function Tests 
No clinically significant changes have been observed in laboratory assessments. 
1.1.6 
Potential Risk of Testicular Injury 
In a nonclinical GLP study of fertility and early embryonic development in rats after daily oral 
administration of NVN1000 there was no adverse findings in male fertility parameters or 
reproductive parameters in either sex. 
Additionally, due to the lack of systemic exposure after dermal administration of SB204 clinically 
and SB206 nonclinically observed to date, the risk of testicular injury is low. 
1.1.7 
Potential Risk to Fetal Development 
Oral administration of NVN1000 drug substance in GLP embryo-fetal developmental toxicity 
studies in rats and rabbits showed minor effects on fetal development only at the highest doses. 
Additionally, due to the lack of systemic exposure after dermal administration of SB204 clinically 
and SB206 nonclinically observed to date, the risk to fetal development is low. 
In prior studies using NVN1000 in different diseases, there have been 6 reported pregnancies, of 
those, two were completed to term with healthy babies. One woman had an elective termination 
of her pregnancy and one woman had a miscarriage. The outcome of the other two pregnancies is 
unknown.  
1.2 
Study Rationale 
MC is benign and generally self-limiting. The average duration of a single lesion is about 2 months; 
however, since the lesions spread easily by autoinoculation from scratching or trauma, the mean 
duration of infection is often more than a year. 
Nitric oxide, an endogenous small molecule, provides localized immunity against foreign 
organisms by acting both as a short lived immune modulator and a direct broad-spectrum 
antimicrobial agent.  Topical exogenous nitric oxide has been investigated as an antimicrobial 
agent due to its broad-spectrum activity, ability to inhibit viral replication, and the ability to readily 
diffuse through cell membranes. 


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There is a significant unmet medical need to treat MC, considering most patients with MC are 
healthy young children. Ablative treatment often causes fear to the children and interfere in 
physician-patient relationships. Repeated ablative treatment become difficult. Using anesthesia 
involves safety risk and costs. Not treating increases further dissemination of the disease. Topical 
application of SB206 which releases nitric oxide may accelerate resolution of MC without causing 
pain, and provide an effective, convenient treatment option of MC. Prevention of further 
dissemination of the disease is also important from public health perspective. 
1.2.1 
Dosing Regimen 
A thin layer of SB206 4%, SB206 8%, SB206 12% or Vehicle Gel will be applied once daily, 
twice daily, or three times a week depending on the assigned cohort, to all affected areas of MC 
for 12 consecutive weeks (84 days). Subjects/caregivers will apply the study drug to all lesions 
identified at Baseline and new lesions that arise during treatment. If a subject clears all lesions 
(confirmed by the Investigator at the next regular scheduled visit), the treatment period will end 
and subjects will be followed for recurrence/new lesions until Week 12/ET.  
All QD dosing should be applied in the morning at home or in the clinic.  All subjects should apply 
their last dose to accommodate the 1to 6 hour window for blood draws.   The exact time of the last 
dose preceding any scheduled visit will be collected. Each dose will consist of NVN1000 Gel or 
Vehicle Gel with an equal volume of hydrogel mixed thoroughly together by the subject or 
caregiver and applied to the lesions and approximately 1 cm surrounding each lesion.  Periocular 
lesions will be treated if the lesions are at least 2 cm from the edge of the eye.  Lesions on the labia 
and penis will not be treated. 
Study personnel will ensure that the subjects or caregivers can identify the treatment area(s) and 
know where to apply the study drug. Subjects will be instructed on the correct use of study drug 
and the amount to apply during Baseline/Day 1 according to the corresponding subject instructions 
for use that will be provided to the subject. 
1.2.2 
Dose Selection Rationale 
Based on the previous nonclinical and clinical safety profiles of NVN1000 topical formulations 
and a nonclinical NOAEL approximately 1.8 fold higher than the highest dose of SB206 to be 
applied in this study, these doses are expected to be safe and well tolerated.  


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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7.3 
Safety Assessments 
7.3.1 
Physical Exam 
A brief physical examination will include heart, lung, and abdomen evaluation. This physical 
examination will be performed at Baseline and at Week 12/ET. Height and weight will only be 
collected at Baseline. Any clinically significant changes in the physical exam from baseline will 
be recorded as AEs. 
7.3.2 
Vital Signs 
Blood pressure and pulse rate will be collected at  Baseline, Week 1, Week 2, Week 4, Week 8 
and Week 12/ET. Any clinically significant changes in vital signs from baseline will be recorded 
as AEs. 
7.3.3 
Clinical Laboratory Tests 
Chemistry and hematology will be collected at Baseline and on the last day of treatment.  Clinically 
significant changes in laboratory values will be recorded as AEs. 
Methemoglobin will be measured at Baseline, Weeks 1, 2, 4, 8 and Week 12/ET using a Masimo 
Rainbow® SET® Rad-57™ pulse co-oximeter. The percent methemoglobin will be displayed on 
the pulse co-oximeter and recorded in the subject’s source documents and in the case report form 
(CRF). Subjects with methemoglobin greater than 3.0% at baseline are not eligible for the study. 
Subjects with a confirmed methemoglobin > 5.0% at any post-baseline visit will be discontinued 
from the study. A confirmed methemoglobin is defined as at least 2 readings within 0.5% of each 
other taken within a 30-minute period. Methemoglobin levels will not be collected as AEs; 
however, if a subject has signs/symptoms of methemoglobinemia and an elevated methemoglobin 
level, methemoglobinemia should be reported as an AE. 
7.3.4 
Pregnancy Testing 
Urine pregnancy testing for females 10 years of age and older will be collected at Screening, 
Baseline, Week 4, Week 8 and Week 12/ET. In addition to having a negative UPT at Baseline (and 
Screening unless Visit 1 is within 7 days of Screening) before the first application of study drug, 
females 10 years of age and older must be willing to use an acceptable form of birth control during 
the study. The following are considered acceptable methods of birth control for this study: 
abstinence with a documented acceptable method of birth control if the subject becomes sexually 
active, oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, 
double-barrier methods (e.g., condom and spermicide), contraceptive injection, Intrauterine 
Device (IUD), hormonal IUD, permanent contraception, same sex partner or partner who has had 
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7.4 
Exposure Assessment 
At select sites, a blood sample will be collected at the Week 12 visit from those subjects who have 
not previously discontinued treatment.  The sample will be collected at a single time point 
approximately 1 to 6 hours following application of study drug.  The final dose may be either be 
done at home or in the clinic.  The time of dose application and sample collection should be 
recorded.  Blood may be collected at the same time as the chemistry and hematology sample, but 
the chemistry and hematology samples should be drawn first. If a subject discontinues treatment 
for any reason (e.g., lesion clearance, subject withdrawal, physician decision) before Visit 6, blood 
should be collected on the last day of treatment. 
Instructions for processing and transporting plasma samples for analysis will be described 
separately. 


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


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


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


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


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


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


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


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


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


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


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11 STATISTICS 
11.1 General Procedures 
Prior to the release of unblinded information through Cohort 3, a detailed, finalized Statistical 
Analysis Plan (SAP) will be completed and placed on file. The Statistical Analysis Plan will 
contain a more comprehensive explanation than that provided here of the methodology used in the 
statistical analyses, as well as the rules and data handling conventions used to perform the analyses 
and the procedure used to account for missing data. 
Safety and efficacy endpoints will be displayed using descriptive statistics and graphical displays. 
For categorical variables, frequencies, and percentages will be presented. The denominator for 
percentage will be based on the number of subjects appropriate for the purpose of analysis. 
Continuous variables will be summarized using descriptive statistics (number of subjects, mean, 
median, standard deviation [SD], minimum, and maximum). Where relevant, 95% confidence 
intervals will be calculated. Although analyses will be descriptive in nature, any statistical tests will 
be conducted at the 0.05 significance level using 2-tailed tests, and nominal p-values will be 
reported.  
11.2 Sample Size 
Approximately 192 subjects, 2 years of age and older, with a minimum of 3 and a maximum of 70 
lesions at baseline will be randomized across a minimum of 3 cohorts. If the third cohort is 
administered 12% BID,  up to an additional 64 subjects will be randomized in a fourth cohort.  
This Phase 2 study was not powered for formal statistical comparisons. The SB206 active dose 
groups will be compared to Vehicle gel. No adjustments will be made for multiplicity. No 
imputations will be utilized for safety or efficacy endpoints 
11.3 Analysis Populations 
The analysis populations include the following: 
The intent-to-treat (ITT) population will consist of all subjects who are randomized. 
The modified intent-to-treat (mITT) population will consist of all subjects who are randomized 
and complete the study treatment (subjects who complete 12 weeks of treatment and subjects who 
complete treatment due to clearance of all molluscum). 
The safety (SAF) population will consist of all patients who take at least one dose of study 
treatment. 
The exposure population will consist of all subjects who receive at least 1 application of active 
study medication and had a blood a blood sample collected and successfully analyzed for the 
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The per-protocol population (PP) will consist of all subjects in the mITT population and have no 
significant protocol deviations that impact the analyses of the efficacy endpoints.  
11.4 Statistical Methods 
11.4.1 
Demographic and Baseline Characteristics 
Subject demographic and Baseline characteristics will be summarized by treatment group for the 
SAF, mITT and ITT populations. Relevant medical history, current medical conditions, and any 
other relevant information will be listed by subject. 
11.4.2 
Efficacy Analysis 
The primary efficacy endpoint is the proportion of subjects achieving complete clearance of all 
molluscum contagiosum at Week 12 (subjects who achieved complete clearance before Week 12 
need to maintain complete clearance at Week 12) which will be analyzed by a logistic regression 
model with treatment, number of lesions at Baseline (3-18; 19-70) and atopic dermatitis history 
(with AD history vs w/o AD history) as factors. The primary analysis will compare each SB206 
dose level with the Vehicle using the mITT population. 
A sensitivity analysis of the primary endpoint will be repeated using the ITT and per-protocol 
population. Other sensitivity analyses may be performed and will be specified in the statistical 
analysis plan. 
Secondary endpoints will be analyzed on the mITT and ITT population as follows: 
• Proportion of subjects achieving complete clearance of all MC at each visit will be 
analyzed using the same logistic regression analysis specified in the primary analysis. 
• Time to complete clearance of all MC will be analyzed using Kaplan Meier methods.  
• Proportion of subjects achieving at least a 75% reduction from baseline in the number of 
MC at each visit will be analyzed using the same logistic regression analysis specified in 
the primary analysis. 
• Mean change and percent change from baseline in number of MC at each visit will be 
analyzed using a mixed-model repeated-measures (MMRM) analysis with treatment as the 
main effect, visit, number of lesions at Baseline (3-18; 19-70) and atopic dermatitis history 
(with AD history vs w/o AD history) as factors and treatment by visit as an interaction 
term. 
Details of all secondary and exploratory endpoints will be specified in the SAP. Additional 
exploratory analyses may be conducted, all analyses will be detailed in the SAP, which will be 
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11.4.3 
Analysis of Safety 
11.4.3.1 
Adverse Events 
All AEs that occur during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities (MedDRA) terminology. Treatment-emergent AEs (TEAEs) 
are defined as AEs with an onset on or after the date of the first study drug dose. Medical history 
noted prior to the first study drug administration that worsen after Baseline will also be reported 
as AEs and included in the summaries.  
Treatment-emergent AEs will be summarized by treatment group, the number of subjects 
reporting a TEAE, System Organ Class (SOC), preferred term, severity, relationship to study 
drug (causality), and seriousness.  When summarizing AEs by severity and relationship, each 
subject will be counted only once within a system organ class or a preferred term by using the 
event with the highest severity and greatest relationship within each classification. 
Serious AEs will be summarized by treatment group, severity, and relationship to study drug, 
and individual SAEs will be listed by subject. In addition, a list of subjects who prematurely 
discontinue from the study due to an AE will be provided. 
11.4.3.2 
Physical Examination 
Changes in physical examination from baseline to end of treatment will be summarized.  Any 
clinically significant changes from Baseline will be documented as an AE. 
11.4.3.3 
 Vital Signs  
Blood pressure and pulse will be summarized by treatment group from Baseline through Week 
12/ET.  Additionally, change from Baseline in vital signs will be summarized at Weeks 1, 2, 4, 8, 
and 12/ET.  Any clinically significant changes from Baseline will be documented as an AE. 
11.4.3.4 
Laboratory Assessments 
Blood chemistry and hematology values will be reported individually at Baseline and day of last 
dose, which may occur at any time during the study.  Therefore, the study day of the last dose will 
be used to assign the laboratory values to the closest study visit (Week 1, 2, 4, 8, or 12).  Laboratory 
test results will be summarized descriptively at Baseline and each visit.  Additionally, shifts from 
Baseline to each visit in laboratory test results based on normal ranges will be summarized with 
descriptive statistics.  The last laboratory evaluation prior to the first dose of study drug will be 
used as Baseline for all laboratory analyses.  Any clinically significant changes from Baseline will 
be documented as an AE. 
Methemoglobin will be reported as a percentage of hemoglobin.  Methemoglobin will be 
summarized descriptively by treatment group at Baseline and Weeks 1, 2, 4, 8 and 12/ET.  
Additionally, the change from baseline in methemoglobin will be summarized by treatment group 
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11.4.3.5 
Urine Pregnancy Tests 
Urine pregnancy tests results for females 10 years of age and older will be presented in data 
listings by subject.   
11.5 Analysis of hMAP3 Plasma Concentrations 
Plasma concentrations of hMAP3, a silicon-containing hydrolyzed monomer of the polymeric 
NVN1000 drug substance will be determined.  Results will be presented in data listings by 
subject.  If quantifiable concentrations are observed, the results will be summarized 
descriptively.  
11.6 Interim Analysis 
After all subjects in Cohort 3 have completed their last study visits, the database for all subjects 
in Cohorts 1-3 will be frozen for purposes of an interim analysis of safety and efficacy data.  
While this interim analysis is being prepared, the study will complete through Cohort 4 and the 
final analysis will be based on all subjects in Cohorts 1-4: Cohort 4 (QD dosing of SB206 8% or 
12% vs. vehicle).   Personnel who are not otherwise involved in the study will prepare the 
unblinded data and summary tables for the interim analysis.  The interim analysis will not impact 
the final analysis since the study does not involve any formal hypothesis testing.   
 


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


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documented in the source document (including the date), and the form signed, before the subject 
undergoes any study-specific procedures. The rights and welfare of the subjects will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study. 
12.5 Records Management 
It is the responsibility of the Investigator to ensure that the study center file is maintained in 
accordance with Section 8 – Essential Documents for the Conduct of a Clinical Trial of the ICH 
Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance and 21 CFR Part 312. 
12.6 Source Documentation 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  Data recorded on the  CRF derived from source documents should be 
consistent with the data recorded on the source documents. 
Clinical data will be entered into a 21 CFR Part 11-compliant data capture system provided by the 
CRO. The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will 
be entered directly from the source documents. 
12.7 Study Files and Record Retention 
It is a Novan requirement that all Investigators participating in clinical studies maintain detailed 
clinical data for one of the following periods, whichever is longest: 
• Country-specific requirements; or 
• A period of at least two years following the last approval of a marketing application 
approved by a Regulatory Authority in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region; or, 
• A period of two years after Novan notifies the Investigator that the data will not be 
submitted for review by any Regulatory Authority. 
The Investigator must not dispose of any records or essential documents relevant to this study 
without either (1) written permission from Novan, or (2) providing an opportunity for Novan to 
collect such records.  The Investigator shall take responsibility for maintaining adequate and 
accurate electronic or hard copy source documents of all observations and data generated during 
this study.  Such documentation is subject to inspection by Novan and relevant regulatory agencies.  
If the Investigator withdraws from the study (e.g., relocation, retirement), all study-related records 
should be transferred to a mutually agreed-upon designee.  Notice of such transfer will be provided 
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13 AUDITING AND MONITORING 
13.1 Auditing 
In addition to the routine monitoring procedures, audits of clinical research activities in accordance 
with standard operating procedures (SOPs) may be performed to evaluate compliance with the 
principles of GCP.  A regulatory authority may also wish to conduct an inspection (during the 
study or even after its completion).  If a regulatory authority requests an inspection, the Investigator 
must inform the CRO immediately that this request has been made. 
Study conduct may be assessed during the course of the study by a Quality Assurance 
representative(s) to ensure that the study is conducted in compliance with the protocol and GCP.  
He/she will be permitted to inspect the study documents (study protocol, study records, 
investigational product, original, study-relevant medical records).  All subject data will be treated 
confidentially. 
13.2 Monitoring 
All aspects of the study will be monitored by the CRO or Novan according to Good Clinical 
Practices (GCP) and Standard Operating Procedures (SOPs) for compliance with applicable 
government regulations, (i.e., informed consent regulations, (21 C.F.R. § 50.20, 1999), and 
Institutional Review Board regulations, (21 C.F.R. § 56.103, 1981)).  Access to all records, both 
during the trial and after trial completion, should be made available to the CRO and Novan at any 
time for review and audit to ensure the integrity of the data.  The Investigator must notify the CRO 
immediately if the responsible IRB has been disqualified or if proceedings leading to 
disqualification have begun. 
The Investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines, applicable informed consent regulations (21 C.F.R. § 50.20, 1999), and in compliance 
with the principles in the Declaration of Helsinki.  Every attempt must be made to follow the 
protocol and to obtain and record all data requested for each subject at the specified times.  If data 
is not recorded per protocol, the reason(s) must be clearly documented on the study records. 
Before study initiation, at a site initiation visit or at a meeting with the Investigator(s), a CRO or 
Novan representative will review the protocol and study records with the Investigator(s) and their 
staff.  During the study, the study monitor will visit the site regularly to check the completeness of 
subject records, the accuracy of entries into the study database, the adherence to the protocol and 
to GCP, the progress of enrollment, to ensure that consent is being sought and obtained in 
compliance with applicable regulations, and that the investigational product is being stored, 
dispensed and accounted for according to specifications.  The Investigator and key trial personnel 
must be available to assist the monitor during these visits. 
The Investigator must give the monitor access to relevant hospital or clinical records to confirm 
their consistency with the study database entries.  No information in these records about the 
identity of the subjects will leave the study center.  Monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, documentation 


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


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


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


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


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


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


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