A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Regimens of CANDIN for Treatment of Common Warts (Verruca Vulgaris)
Phase: PHASE2
Conditions: Warts
Sponsor: Nielsen BioSciences, Inc.

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Protocol Final version 5.0: 06Dec2016 
 
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 A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying 
Regimens of CANDIN for Treatment of Common Warts (Verruca vulgaris) 
 
 
 
 
PROTOCOL # CFW-2D 
 
 
FINAL 
 
 
 
VERSION 5.0 06Dec2016 
 
Previous version  
4.0 dated 13Jul2015 
3.0 dated 23Jun2014 
2.0 dated 26May2014 
1.0 dated 02Apr2014 
 
 
 
 
 
 
Sponsor: 
 
Nielsen BioSciences Inc. 
                      
 
7229 Convoy Court 
                      
 
San Diego, CA, 92111 
United States of America 
Tel:  
(858) 571-2726 
Fax:  
(858) 571-2759 
 
  
 
 
 
 
 
  
 
 
 
       
 
       
 
 
 

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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ................................................................................................................................ 2 
PROTOCOL APPROVAL .............................................................................................................................. 5 
INVESTIGATOR SIGNATURE PAGE .......................................................................................................... 6 
LIST OF ABBREVIATIONS......................................................................................................................... 11 
SUMMARY .................................................................................................................................................. 12 
1 
BACKGROUND .................................................................................................................................. 18 
1.1 
Common Warts .......................................................................................................................... 18 
1.2 
Treating Common Warts ............................................................................................................ 18 
1.3 
Candida Albicans Skin Test Antigen for Cellular Hypersensitivity (Candin®) ............................ 19 
1.4 
CANDIN for the Treatment of Common Warts .......................................................................... 19 
2 
STUDY HYPOTHESIS AND OBJECTIVE(S) .................................................................................... 21 
3 
STUDY ENDPOINTS ......................................................................................................................... 22 
3.1 
Primary Endpoint ....................................................................................................................... 22 
3.2 
Secondary Endpoints ................................................................................................................. 22 
3.3 
Exploratory Endpoints ................................................................................................................ 22 
4 
STUDY DESIGN ................................................................................................................................. 23 
5 
STUDY POPULATION ....................................................................................................................... 23 
5.1 
Inclusion Criteria ........................................................................................................................ 23 
5.2 
Exclusion Criteria ....................................................................................................................... 24 
5.3 
Discontinuations ........................................................................................................................ 25 
6 
TREATMENT ...................................................................................................................................... 26 
6.1 
Treatment Administered ............................................................................................................ 26 
6.2 
Materials and Supplies .............................................................................................................. 27 
6.2.1 
Study Products ...................................................................................................................... 27 
6.2.2 
Method of Assignment to Treatment ..................................................................................... 28 
6.2.3 
Rationale for Selection and Timing of Doses in the Study .................................................... 29 
6.2.4 
Breaking of Study Blinding .................................................................................................... 29 
6.2.5 
Concomitant Therapy ............................................................................................................ 30 
6.2.6 
Assessment of Compliance ................................................................................................... 30 
7 
STUDY PROCEDURES ..................................................................................................................... 31 
7.1 
Screening Visits 1 and 2 (Day -30 to Baseline) ......................................................................... 31 
7.2 
Baseline Visit (V3), Day 1 .......................................................................................................... 31 
7.3 
Injection Visits 4 to 12 (± 2 days) ............................................................................................... 32 
7.4 
Efficacy Evaluation Visit 13 (± 3 days) ...................................................................................... 33 
7.5 
Follow-up Visits: Visit 14 (± 3 days) and Visit 15 (± 7 days) ...................................................... 33 
7.6 
Early Termination Visit ............................................................................................................... 34 

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7.7 
Treatment Procedure ................................................................................................................. 34 
7.8 
Vital Signs .................................................................................................................................. 34 
7.9 
Dermatologic Examination ......................................................................................................... 35 
7.10 
Physical Examination ................................................................................................................. 35 
7.11 
Medical Photographs ................................................................................................................. 35 
7.12 
DTH Challenge .......................................................................................................................... 35 
8 
EFFICACY EVALUATIONS ............................................................................................................... 36 
8.1 
Common Wart Evaluations ........................................................................................................ 36 
8.1.1 
Common wart measurement ................................................................................................. 36 
8.1.2 
Evaluation of primary injected wart status ............................................................................. 36 
8.1.3 
Evaluation of presence or absence of common warts other than the measured common 
warts 
37 
8.1.4 
Presence or absence of common warts in designated anatomical areas ............................. 37 
9 
SAFETY EVALUATIONS ................................................................................................................... 37 
9.1 
Subject Diaries ........................................................................................................................... 38 
9.2 
Adverse Events .......................................................................................................................... 38 
9.2.1 
Adverse Events Causality ..................................................................................................... 39 
9.2.2 
Adverse Events Severity ....................................................................................................... 40 
9.3 
Serious Adverse Events ............................................................................................................ 40 
9.3.1 
SAE Reporting: ...................................................................................................................... 41 
9.4 
Pregnancy Reporting ................................................................................................................. 42 
9.5 
Hypopigmentation and Scarring Assessments .......................................................................... 42 
9.6 
Laboratory Tests ........................................................................................................................ 42 
9.6.1 
Pregnancy Test ..................................................................................................................... 42 
9.6.2 
Clinical Chemistry Analysis ................................................................................................... 43 
9.6.3 
Clinical Haematology Analysis .............................................................................................. 43 
9.6.4 
Urinalysis ............................................................................................................................... 43 
9.6.5 
Biomarkers ............................................................................................................................ 43 
9.7 
Stopping Rules .......................................................................................................................... 43 
9.7.1 
Individual Stopping Rules ...................................................................................................... 43 
9.7.2 
Cohort Stopping Rules .......................................................................................................... 44 
10 
DATA QUALITY ASSURANCE/SITE MONITORING ........................................................................ 45 
11 
DATA COLLECTION AND RETENTION ........................................................................................... 45 
12 
CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS ..................................... 46 
13 
INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS .............................................................. 46 
14 
SAMPLE SIZE AND STATISTICAL CONSIDERATIONS .................................................................. 46 
14.1 
Determination of Sample Size ................................................................................................... 46 
14.2 
Analysis Populations .................................................................................................................. 46 
14.3 
Subject Disposition .................................................................................................................... 47 
14.4 
Demographic and Baseline Characteristic ................................................................................ 47 
14.5 
Statistical Analysis ..................................................................................................................... 47 
14.5.1 
Efficacy analysis ................................................................................................................ 47 
14.5.2 
Safety Analysis .................................................................................................................. 48 

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14.5.3 
Interim analysis ................................................................................................................. 49 
15 
ETHICS .............................................................................................................................................. 49 
15.1 
Local Regulations/Declaration of Helsinki ................................................................................. 49 
15.2 
Ethical Review ........................................................................................................................... 50 
15.3 
Informed Consent ...................................................................................................................... 50 
16 
PUBLICATION POLICY ..................................................................................................................... 50 
17 
REFERENCES ................................................................................................................................... 50 
18 
APPENDIX A  Study Flow Chart ........................................................................................................ 52 
 

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PROTOCOL APPROVAL 
 
 
A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying 
Regimens of CANDIN for Treatment of Common Warts (Verruca vulgaris) 
 
 
 
Protocol number:  
CFW-2D, Version 5.0 
 
 
 
Protocol Final Date:  06Dec2016 
 
 
The signatures below constitute the approval of this protocol and the attachments, and provide the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, including 
all statements regarding confidentiality, and according to local legal and regulatory requirements and 
applicable Canadian regulations, U.S. federal regulations and ICH guidelines. 
 
 
 
 

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INVESTIGATOR SIGNATURE PAGE 
 
A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying 
Regimens of CANDIN for Treatment of Common Warts (Verruca vulgaris) 
 
 
 
Protocol number:  
CFW-2D, Version 5.0 
 
 
 
Protocol Final Date:  06Dec2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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SUMMARY OF CHANGES   
 
 
AMENDMENT 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
”. 
 

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AMENDMENT 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 HISTORY 
 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
AIDS 
Acquired immunodeficiency syndrome 
CANDIN 
Candida albicans Skin Test Antigen for Cellular Hypersensitivity 
DNCB 
Dinitrochlorobenzene 
DPCP 
Diphenylcyclopropenone 
DTH 
Delayed Type Hypersensitivity 
eCRF 
Electronic case report form  
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HPV 
Human Papilloma Virus 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
IP 
Investigational Product 
MedDRA 
Medical Dictionary for Regulatory Activities 
OTC 
Over the counter 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOC 
System Organ Class 
S.G. 
Specific gravity 
TEAE 
Treatment-Emergent Adverse Event 
UBG 
Urobilinogen 
 
 
 

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SUMMARY  
 
Title: 
A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety 
and Efficacy of Varying Regimens of CANDIN for Treatment of Common Warts 
(Verruca vulgaris) 
 
 
Phase: 
IIa 
 
Study Treatment and 
Administration: 
Cohort 1: 0.3 mL of CANDIN (Candida albicans Skin Test Antigen for Cellular 
Hypersensitivity) or Placebo administered intralesionally in the largest common 
wart  
 
 
Cohort 2: 0.5 mL of CANDIN or Placebo administered intralesionally in the 
largest common wart  
 
 
Cohort 3: 0.3 mL of CANDIN or Placebo administered intralesionally in up to 4 
warts at the same visit (up to 1.2 mL total injected volume) 
 
Population: 
Approximately 156, male or female subjects aged 18 to 65, with 3 to 20 common 
warts on hands, feet (excluding soles), limbs and/or trunk will be included in this 
study 
 
Number of Sites: 
Approximately 15 centers in USA will participate in this study  
 
Study Duration: 
Subjects will be treated for a maximum of 29 weeks followed by a 16-week 
observation period for a total of 45 weeks, excluding the 4-week screening period. 
 
Hypothesis: 
The null hypothesis for this study is that the CANDIN treatments are not 
significantly different from placebo under these experimental conditions 
 
Objectives: 
 
The primary objective is to assess the efficacy of CANDIN treatment in subjects with common warts by 
evaluating the number and proportion of subjects with the primary injected wart(s) completely resolved.  
 
The secondary objectives are: 
 
1. To assess the safety and tolerability of CANDIN  
 
2. 
 
 
 
 
 
 
 
 
 
 
 
  
 

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Endpoints: 
 
Primary Endpoint:  
 
 
The number and proportion of subjects with the primary injected wart(s) completely 
resolved at any treatment or Follow-up Visit 
 
Secondary Endpoints:   
 
1. Incidence of site injection Adverse Event (AE) for all subjects and Treatment-Emergent Adverse 
Event (TEAE) for subjects randomized to CANDIN 
 
 

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Overall Study Design 
 
This is a placebo-controlled, double-blind (subject, Investigator, and site staff with the exception of 
unblinded dedicated staff to handle study medication), phase 2a study with 3 dose cohorts, randomized 
(concealed) to CANDIN or placebo (3:1). Main study will be up to 20 weeks (10 doses administered every 
other week) or until a subject has complete resolution of all injectable common warts. Subjects who cannot 
tolerate dosing every 2 weeks due to a local tolerance issue may be injected at 3-week intervals for up to 
10 doses, increasing the length of the study to 29 weeks. Subjects will be followed for 4 months after final 
injection(s) for evidence of new or reoccurring warts and for safety evaluation.  
 
Inclusion Criteria 
 
Subjects may be eligible if they meet all the following inclusion criteria at the Screening and Baseline 
Visits unless specified otherwise:  
 
1. Men or women between the ages of 18 and 65 years inclusively at time of consent 
 
2. Subjects presenting with 3 to 20 injectable common warts (verruca vulgaris) for at least 12 
weeks  at the time of the Baseline Visit 
 
3. Subject’s common warts for injection must measure between 3 and 20 mm at Baseline Visit 
and be located on hands, feet (excluding soles), limbs, and/or trunk.  Flat, plantar, facial, 
periungual, genital warts or warts in region of pre-existing inflammatory condition are excluded 
from injection  
 
4. Subjects enrolled into Cohort 3 must have common warts for injection in at least 2 different 
anatomical regions defined as: left arm, right arm, left hand, right hand, left leg, right leg, left 
foot (excluding sole), right foot (excluding sole) and torso  
 
5. Subject, male or female is willing to use effective contraceptive method for at least 30 days 

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before the Baseline Visit and at least 30 days after the last study drug administration unless 
not of childbearing potential as defined as post-menopausal for at least 2 years (females) or 
surgically sterile (tubal ligation, oophorectomy, or hysterectomy for females, and vasectomy for 
males).  The only contraceptive use exceptions would be individuals in exclusive same sex 
partnerships and individuals who agree to remain non-sexually active for the duration of the 
study. Acceptable contraceptive methods for subjects include:  
a. Barrier methods, such as condom, sponge or diaphragm, combined with spermicide in foam, 
gel or cream;  
b. Hormonal contraception (oral, intramuscular, implant or transdermal which includes Depo-
Provera, Evra and Nuvaring);  
c. Intrauterine device (IUD) 
 
Female subjects of childbearing potential in a same sex partnership or who are abstinent will 
still receive pregnancy test as outlined in Appendix A. 
 
6. Mentally and legally capable of giving informed consent prior to any study related procedures 
 
Exclusion Criteria 
 
Subjects will not be eligible if they meet any of the following criteria at the Screening or Baseline Visits 
unless specified otherwise: 
 
1. 
Presence of systemic or localized diseases, conditions, or medications that could interfere with 
assessment of safety and efficacy or that compromise immune function including psoriasis 
 
2. 
Subject has been diagnosed with diabetes mellitus 
 
3. 
Subject has a history of keloid formation 
 
4. 
Injectable common wart(s) located in areas with existing dermatologic conditions (such as 
psoriasis) or with an underlying inflammatory conditions (such as arthritic joints), or tattoos or 
implants/piercing/hardware or marking that may conceal responses or reactions are excluded 
from injection 
 
5. 
Existing/planned pregnancy, childbirth in the past six months prior to the Baseline Visit, or 
breast feeding, or plan on donating eggs or sperm during the study and in the month following 
the last injection 
 
6. 
Treatment of warts with liquid nitrogen, carbon dioxide, electrodessication, laser, surgery, 
simple occlusion (e.g. duct tape), salicylic or related acids, OTC treatments, cantharidin, or 
other treatments (other than immunotherapy or those intended to stimulate immune response) 
within 4 weeks of the Baseline Visit 
 
7. 
Treatment with immunotherapy (DPCP, DNCB or other), imiquimod, 5-fluorouracil, bleomycin, 
podophyllin or any other wart immunotherapy or treatment designed to stimulate immune 
response (except for treatments already listed in exclusion criterion 6) within 12 weeks of the 
Baseline Visit  
 
8. 
Recalcitrant warts defined as those not successfully treated by five or more treatments 

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(excluding OTC treatments).  
 
9. 
Abnormal (low < 5 mm or high >25 mm) baseline result to the Delayed Type Hypersensitivity 
(DTH) test  
 
10. Subject has a condition or treatment resulting in being immunocompromised 
 
11. Systemic treatment (such as oral or injected) with cimetidine, zinc supplements at a dose 
higher than 20 mg of elemental zinc daily or an immunosuppressive drug (such as: 
azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept, systemic 
steroids, etc.) within 12 weeks of the Baseline Visit.  Note that subjects should not discontinue 
use of immunosuppressive therapy for the purpose of entering the study as the underlying 
conditions also could interfere with the study. 
 
12. Subject has used any investigational agent within 30 days prior to the Baseline Visit or within 
5 half-lives of that investigational agent prior to the Baseline Visit (whichever is longer) 
 
13. Previous treatment of warts with any type of intralesional injection with candida extract 
(including CANDIN) 
 
Statistical Considerations 
 
The primary endpoint is the number and proportion of subjects with complete resolution of the primary 
injected wart(s). The proportion of subjects with the complete resolution of treated warts will be compared 
among all treatment groups using the Cochran-Mantel-Haenszel test with a stratification factor of single 
versus multiple anatomical regions. In addition each active treatment will be compared with the pooled 
placebo in a similar manner.  There will be no adjustment of the type 1 error for multiple comparisons.  
 
Sample Size Determination 
 
A total of approximately 156 subjects will be enrolled into the study with approximately 52 subjects in each 
active treatment arm and the pooled placebo group. One assumes that the pooled placebo arm has a 24% 
complete resolution rate and one of the active treatment arms has a complete resolution rate of 70%. The 
statistical comparison between each active treatment and the pooled placebo will be conducted at the 0.05 
significance level. It is assumed that at least 90% of the subjects will either complete the study or reach 
complete resolution.  A sample size of approximately 52 per arm will provide 94% power to detect a 
statistically significant difference between an active treatment and the pooled placebo. The assumed 

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1 BACKGROUND 
1.1 Common Warts 
Verruca vulgaris, common warts, are caused by the human papilloma virus (HPV). HPV infects epithelial 
cells and, in the case of common warts, cause proliferation of the fully differentiated epithelium resulting in 
clinically evident warty papules. Most authors agree that the prevalence of non-genital warts is between 7 
and 10% in the US. Young people are preferentially affected, with the peak incidence being reported 
between the ages of 12 and 16 years. Common warts are least common among infants and the elderly.1-7 
Common warts occur most frequently on hands and feet, less frequently on limbs, torso or face where flat 
warts are more common.5, 7 New common warts frequently regress spontaneously with reports of roughly 
60% regressing within two years, and roughly 30% of subjects experiencing spontaneous regression of at 
least one wart during a nine month period.1, 2, 7, 8 However, the remaining roughly 40% may remain for years. 
While many subjects are instructed to wait and see if the warts resolve spontaneously, warts can bleed, 
itch, be painful and disfiguring, with 52% of subjects experiencing moderate to severe discomfort and 81% 
being moderately to extremely embarrassed by the presence of their warts.7 Additionally, untreated warts 
serves as a reservoir for continued shedding of contagious papilloma virus. 
1.2 Treating Common Warts 

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1.3 Candida Albicans Skin Test Antigen for Cellular Hypersensitivity (Candin®) 
CANDIN is currently marketed in the United States indicated for use as a recall antigen for detecting DTH 
by intradermal injection of 0.1 mL. The product may be useful in assessing the cellular immune response 
in individuals suspected as having decreased immune responses of this type, such as those with AIDS, 
HIV, and cancer. Local reactions observed in the development of CANDIN for DTH included redness, 
swelling, pruritus, vesiculation, weeping edema, excoriation, induration, and discoloration of the skin. 
Immediate hypersensitivity has been observed within 20 minutes of injection characterized as an 
edematous hive with a surrounding zone of erythema. Up to approximately 20% of subjects had lesions of 
10-24 mm diameter and another group of up to approximately 13% had lesions of less than 10 mm diameter. 
1.4 CANDIN for the Treatment of Common Warts 
 

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2 STUDY HYPOTHESIS AND OBJECTIVE(S) 
Hypothesis:  
 
The null hypothesis for this study is that the CANDIN treatments are not significantly different from placebo 
under these experimental conditions 
 
Objective(s): 
 
The primary objective is to assess the efficacy of CANDIN treatment in subjects with common warts by 
evaluating the number and proportion of subjects with the primary injected wart(s) completely resolved.  
 
The secondary objectives are: 
 
1. To assess the safety and tolerability of CANDIN  
 
 

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3 STUDY ENDPOINTS 
3.1 Primary Endpoint 
 
The number and proportion of subjects with the primary injected wart(s) completely 
resolved at any treatment or Follow-up Visit.  
3.2 Secondary Endpoints 
1. Incidence of site injection AE for all subjects and TEAE for subjects randomized to CANDIN 
 
 
 
 
 
 
 
 

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4 STUDY DESIGN  
This is a placebo-controlled, double-blind (subject, Investigator, and site staff with the exception of 
unblinded dedicated staff to handle study medication), phase 2a study with 3 dose cohorts, randomized 
(concealed) to CANDIN or placebo (3:1). Main study will be up to 20 weeks (10 doses administered every 
other week) or until a subject has complete resolution of all injected common warts. Subjects who cannot 
tolerate dosing every 2 weeks due to a local tolerance issue may be injected at 3-week intervals for up to 
10 doses, increasing the length of the study to 29 weeks (+/- study windows). Subjects will be followed for 
4 months after final injection(s) for evidence of new or reoccurring warts and for safety evaluation. 
5 STUDY POPULATION  
Approximately 156, male or female subjects aged 18 to 65 inclusively at the signature of consent with 3 to 
20 common warts on hands, feet (excluding soles), limbs and/or trunk will be included in this study in order 
to complete with approximately 115 subjects. Drop-outs will not be replaced.  Additional subjects may be 
added to ensure approximately 115 subject complete the study in the event an investigator or site 
discontinues participation in the study 
5.1 Inclusion Criteria 
Subjects may be eligible if they meet all the following inclusion criteria at the Screening and Baseline Visits 
unless specified otherwise:  
 
1. Men or women between the ages of 18 and 65 years inclusively at time of consent 
 
2. Subjects presenting with 3 to 20 injectable common warts (verruca vulgaris) for at least 12 
weeks  at the time of the Baseline Visit 
 
3. Subject’s common warts for injection must measure between 3 and 20 mm at Baseline Visit 
and be located on hands, feet (excluding soles), limbs, and/or trunk.  Flat, plantar, facial, 
periungual, genital warts or warts in region of pre-existing inflammatory condition are excluded 
from injection 
 
4. Subjects enrolled into Cohort 3 must have common warts for injection in at least 2 different 
anatomic regions defined as: left arm, right arm, left hand, right hand, left leg, right leg, left foot 
(excluding sole), right foot (excluding sole) and torso 
 
5. Subject, male or female is willing to use effective contraceptive method for at least 30 days 
before the Baseline Visit and at least 30 days after the last study drug administration unless 
not of childbearing potential as defined as post-menopausal for at least 2 years (females) or 
surgically sterile (tubal ligation, oophorectomy, or hysterectomy for females, and vasectomy for 
males).  The only contraceptive usage exceptions would be individuals in exclusive same sex 
partnerships and individuals who agree to remain non-sexually active for the duration of the 
study. Acceptable contraceptive methods for subjects include:  
a. Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, 
gel or cream;  
b. Hormonal contraception (oral, intramuscular, implant or transdermal which includes Depo-
Provera, Evra and Nuvaring);  
c. Intrauterine device (IUD) 

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Confidential and proprietary.  Permission should be obtained before any reproduction. 
 
Female subjects of childbearing potential in a same sex partnership or who are abstinent will 
still receive pregnancy test as outlined in Appendix A. 
  
6. Mentally and legally capable of giving informed consent prior to any study related procedures 
5.2 Exclusion Criteria 
Subjects will not be eligible if they meet any of the following criteria at the Screening and Baseline Visits 
unless specified otherwise:  
1. 
Presence of systemic or localized diseases, conditions, or medications that could interfere 
with assessment of safety and efficacy or that compromise immune function including 
psoriasis 
 
2. 
Subject has been diagnosed with diabetes mellitus 
 
3. 
Subject has a history of keloid formation 
 
4. 
Injectable common wart(s) located in areas with existing dermatologic conditions (such as 
psoriasis) or with an underlying inflammatory conditions (such as arthritic joints), or tattoos or 
implants/piercing/hardware or marking that may conceal responses or reactions are excluded 
from injection. 
 
5. 
Existing/planned pregnancy, childbirth in the past six months prior to the Baseline Visit, or 
breast feeding, or plan on donating eggs or sperm during the study and in the month following 
the last injection. 
 
6. Treatment of warts with liquid nitrogen, carbon dioxide, electrodessication, laser, surgery, 
simple occlusion (e.g. duct tape), salicylic or related acids, OTC treatments, cantharidin, or 
other treatments (other than immunotherapy or those intended to stimulate immune response) 
within 4 weeks of the Baseline Visit 
 
7. Treatment with immunotherapy (DPCP, DNCB or other), imiquimod, 5-fluorouracil, bleomycin, 
podophyllin or any other wart immunotherapy or treatment designed to stimulate immune 
response (except for treatments already listed in exclusion criterion 6) within 12 weeks of the 
Baseline Visit  
 
8. Recalcitrant warts defined as those not successfully treated by five or more treatments 
(excluding OTC treatments).  
 
9. 
Abnormal (low < 5 mm or high >25 mm) baseline result to the Delayed Type Hypersensitivity 
(DTH) test  
 
10. Subject has a condition or treatment resulting in being immunocompromised 
 
11. Systemic treatment (such as oral or injected) with cimetidine, zinc supplements at a dose 
higher than 20 mg of elemental zinc daily  or an immunosuppressive drug (such as: 
azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept, systemic 
steroids, etc.) within 12 weeks of the Baseline Visit.  Note that subjects should not discontinue 

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use of immunosuppressive therapy for the purpose of entering the study as the underlying 
conditions also could interfere with the study. 
 
12. Subject has used any investigational agent within 30 days prior to the Baseline Visit or within 
5 half-lives of that investigational agent prior to the Baseline Visit (whichever is longer) 
 
13. Previous treatment of warts by intralesional injection with any type of candida extract (including 
CANDIN) 
5.3 Discontinuations 
Subjects have the right to withdraw from the study at any time for any reason without penalty. The 
Investigator also has the right to withdraw subjects from the study if he/she feels it is in the best interest of 
the subject or if the subject is uncooperative or non-compliant. It is understood by all concerned that an 
excessive rate of withdrawal can render the study un-interpretable; therefore, unnecessary withdrawal of 
subjects should be avoided. Should a subject decide to withdraw or if the Investigator decides a subject 
should be withdrawn, all efforts will be made to complete and report the observations as required in Section 
7.6 - Early Termination Visit. 
 
An Early Termination Visit should be completed at the time of the decision to withdraw the subject, or as 
soon as possible thereafter, and the reason for withdrawal from the study should be documented. If the 
reason for removal of a subject is an AE or an abnormal laboratory test result, the principal specific event 
or test will be recorded as the reason for study discontinuation. If this decision is made because of a related 
SAE, the study drug is to be discontinued and appropriate medical interventions are to be taken. The 
Investigator will notify the Sponsor immediately. All unresolved, possibly related and related AEs and SAEs 
will be followed until resolution, or until the Investigator deems the event(s) to be chronic or stable, or until 
the subject is lost to follow-up. 
 
The criteria for enrollment must be followed explicitly. If a subject who does not meet enrollment criteria is 
inadvertently enrolled, that subject should be discontinued from the study. If this subject received CANDIN, 
he/she should come back, if possible within 1 week of the last visit, for safety and efficacy evaluations as 
required in Section 7.6 - Early Termination Visit. 
 
Reasons for study drug discontinuation include: 
 
The Investigator decides that the subject should be withdrawn (see above). 
 
The attending or general physician requests that the subject be withdrawn from the study 
 
The subject for any reason requires or receives treatment with another therapeutic agent or treatment 
for their warts. In this case, discontinuation from the study occurs immediately upon introduction of the 
new agent 
 
The subject for any reason requires treatment with concomitant medication that is excluded on study. 
In this case, discontinuation from the study occurs immediately upon introduction of the concomitant 
medication. The Early Termination Visit should occur before the introduction of the concomitant 
medication if possible. 
 
The subject is lost to follow-up, in this case, a reasonable attempt to contact the subject and ascertain 
his/her status must be made and these attempts must be documented. The effort will include three or 
more documented attempts then a certified letter requesting the subject contact the site. The 

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Investigator or one of his/her staff members should contact the subject either by telephone, e-mail, or 
letter to determine as completely as possible the reason for the withdrawal and to schedule the Early 
Termination Visit. If the subject intends to withdraw from the study, the Early Termination Visit should 
occur as soon as possible. 
 
The Sponsor or Regulatory Authorities, for any reason, stops the study. All subjects will be discontinued 
from the study and notified of the reasons for the discontinuation. Subjects may be asked to continue 
with follow-up visits as outlined in Appendix A or to complete the Early Termination Visit. 
 
The Sponsor, Investigator, or Regulatory Authorities, for any reason, discontinues a site’s participation. 
All subjects at that site will be discontinued from the study (unless an alternative, local site is active) 
and notified of the reasons for the discontinuation. Subjects may be asked to complete the Early 
Termination Visit and may continue with one or both follow-up visits as outlined in Appendix A. 
 
Pregnancy at any time during the study. The subject will be followed as outlined in Section 9.4 - 
Pregnancy Reporting. 
 
The subject may withdraw from the study for any other reason, including withdrawal of consent. See 
above. 
6 TREATMENT 
6.1 Treatment Administered 
Subjects who fulfill all the inclusion and none of the exclusion criteria may be accepted in the study. Each 
subject should read and sign an informed consent form prior to any screening procedures being performed. 
This study involves a comparison of an intralesional injection of CANDIN with an intralesional injection of 
placebo (unpreserved normal saline solution) in common warts. Subjects will receive one (Cohorts 1 and 
2) or more (Cohort 3) intralesional injections every two weeks (14 +/- 2 days) at the region of the 
interdigitated base of wart (epidermal/dermal junction) for up to 20 weeks (a maximum of 10 doses per 
subject) or up to resolution of all injectable warts. Subjects who experience local tolerance issues when 
dosing is performed at 2-week intervals may be injected at 3-week intervals (21 +/- 2 days) also for a 
maximum of 10 doses per subject.  
 
Subjects will be included in three cohorts as follows: 
 
1. 
Cohort 1:  Approximately 52 subjects will receive 0.3 mL of either CANDIN (n=39) or 
placebo (n=13) intralesionally in the largest common wart (primary) every second week (14 
+/- 2 days) for a maximum of 10 injections. If the primary common wart exhibits a complete 
response, the second largest injectable common wart of all anatomical regions will be 
injected with CANDIN at the same dose. If the second largest common wart exhibits a 
complete response, the third largest of all anatomical regions will be injected. If an injected 
wart recurs after exhibiting a complete response, it will be re-injected instead of the non-
primary injected wart that was injected at the previous visit. This injection strategy will be 
repeated for a maximum of 10 injections per subject or until all injectable common warts 
exhibit a complete response, if it occurs before all 10 injections are used.   
 
2. 
Cohort 2: Approximately 52 subjects will receive 0.5 mL of either CANDIN (n=39) or 
placebo (n=13) intralesionally in the largest common wart every second week (14 +/- 2 
days) for a maximum of 10 injections. If the primary common wart exhibits a complete 

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response the second largest injectable common wart of all anatomical regions will be 
injected with CANDIN at the same dose. If the second largest common wart exhibits a 
complete response the third largest wart of all anatomical regions will be injected. If an 
injected wart recurs after exhibiting a complete response, it will be re-injected instead of 
the non-primary injected wart that was injected at the previous visit.  This injection strategy 
will be repeated for a maximum of 10 injections per subject or until all injectable common 
warts exhibit a complete response, if it occurs before all 10 injections are used.    
 
3. 
Cohort 3: If the safety data of the 2nd cohort support continuation of the study (defined as 
medical assessment of the first eight (8) subjects (of cohort 2) completing three (3) 
injections), the approximately 52 subjects of cohort 3 will receive either 0.3 mL/wart 
CANDIN (n=39) or placebo (n=13) (total per visit ≤ 1.2 mL). Subjects in cohort 3 must have 
injectable common warts in at least 2 different anatomic regions. CANDIN or placebo will 
be injected under the largest wart (primary) per major anatomical region (left or right; arm, 
hand, leg, foot (excluding sole) or the torso) for a minimum of two (2) and a maximum of 
four (4) injections per visit every second week (14 +/- 2 days) for a maximum of 10 visits 
with injections. No more than one wart per anatomical region will be injected on any given 
visit.  If any primary injected wart exhibits a complete response, the next largest injectable 
common wart will be injected with CANDIN at the same dose (maximum of 4 injections per 
visit) providing the new injectable wart is not within the same anatomical region as other 
currently injected warts. If an injected wart recurs after exhibiting a complete response, it 
will be re-injected instead of the non-primary injected wart that was injected at the previous 
visit. This injection strategy will be repeated for a maximum total of 10 injection visits per 
subject or until all injectable common warts exhibit a complete response, if it occurs before 
the end of the 10 injection visits.  
6.2 Materials and Supplies 
6.2.1 Study Products 
DTH Testing: CANDIN (Candida albicans Skin Test Antigen for Cellular Hypersensitivity) used according 
to the US approved labeling. CANDIN is a clear, colorless, sterile aqueous solution, pH of 8.0-8.5, packaged 
in 1 mL multidose glass vials. Each vial delivers 10 x 0.1 mL dose. CANDIN will be provided by Nielsen 
BioSciences, Inc. 
 
Investigational Product: CANDIN used as the Investigational Product (IP). CANDIN is a clear, colorless, 
sterile aqueous solution, pH of 8.0-8.5, packaged in 1 mL multidose glass vials. Each vial delivers 10 x 0.1 
mL dose. CANDIN will be provided by Nielsen BioSciences, Inc. 
 
Placebo: 0.9% sodium chloride injection, USP, preservative free for injection 
 
 used as the placebo. It will be provided by Nielsen BioSciences, Inc.  Each vial will 
be used for a single injection (once) since the contents are not preserved. 
 
The Investigator will be responsible for drug accountability. After verification of the drug accountability by 
the Sponsor, the Investigator will return the remaining study product (used and unused vials) to the 
Sponsor.  
 
CANDIN for DTH testing and for use as the IP will be provided by the Sponsor to the Investigator and will 
be kept on site in a secure temperature controlled refrigerated space (2-8 °C). It will only be dispensed to 

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subjects enrolled on the trial under the supervision of the Investigator. Refrigerator temperature will be 
monitored and recorded in a log. The Investigator is responsible for maintaining accurate records of the 
dispensing of study medication.  
 
 
 
 
 
 
 
  
 
 
 
 
  
6.2.2 Method of Assignment to Treatment 
This is a double-blind study defined as blinding of subjects, investigators, and site personnel not involved 
in study drug preparation and accountability. 
 
 
 Randomization will be unbalanced (3:1) in favor of CANDIN. 
 
 
)
 
 The subjects will be randomly assigned to cohorts first and then to treatment according to the 
following randomization table.  The purpose is to ensure that subject characteristics are as comparable as 
possible between different cohorts.  
 
 

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The investigational site will assign each subject a subject identifier number during screening that will be 
used on all subject documentation throughout the study. Numbers will be assigned in ascending order using 
Sponsor’s numbering system.  
6.2.4 Breaking of Study Blinding 
 
This will be a double-blind study; the Investigators performing the injection, site personnel performing or 
recording study assessments, site study coordinators, and subjects will remain blinded to active versus 
control treatment.  

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6.2.6 Assessment of Compliance 
Since all study drug will be administered on site, compliance will be directly monitored by the study staff. 

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7 STUDY PROCEDURES 
7.1 Screening Visits 1 and 2 (Day -30 to Baseline) 

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7.8 Vital Signs 
The following vital signs will be recorded at Screening (V1), Baseline (V3) and Injection (V4-V12) Visits 
prior to treatment and Efficacy Evaluation Visit (V13) after an approximately 5 minutes resting period in a 
seated position:  
 
 
Systolic and diastolic blood pressure (mm Hg),  
 
Pulse (bpm),  
 
Body temperature (°C) 
 
The weight (kg or lbs) and height (cm or inches) will be recorded at the Screening Visit (V1) only. 

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7.10 Physical Examination 
A physical examination will be performed at Screening (V1) and Efficacy Evaluation Visit (V13). The 
following sites/systems will be included in the physical examination. Each system will be scored as 
normal/abnormal. Pertinent details must be recorded for any clinically significant findings, in order to be 
added as medical history or an AE.  
 
 
General appearance 
 
Skin 
 
Eyes, Ears, Nose, Throat 
 
Head, Neck, Thyroid 
 
Lymphatic 
 
Cardiovascular 
 
Lungs, Chest 
 
Abdomen 
 
Extremities 
 
Musculoskeletal 
 
Neurologic 
7.12 DTH Challenge 
At Screening Visit 1 (V1), the DTH test will be done by administering a single intradermal injection of 
CANDIN (0.1mL) on the volar surface of the forearm or on the outer aspect of the upper arm, at least 2 cm 
away from any primary injectable wart(s). The skin should be cleansed with 70% alcohol before applying 
the skin test. The intradermal injection must be given as superficially as possible causing a distinct, sharply 
defined bleb. An unreliable reaction may result if the product is injected subcutaneously. The subject will 

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be asked to remain in the clinic for 30 minutes after receiving the injection of CANDIN for the DTH test, to 
assess any immediate reactions. A DTH diary will be handed to the subject, in order to capture any delayed 
reactions, prior to Screening Visit 2 (V2). 
 
The test should be read on V2 at (48 ± 4 hours post DTH challenge injection that occurred at V1) by visually 
inspecting the test site and palpating the indurated area. Measurements should be made across two 
diameters. The mean of the longest and midpoint orthogonal diameters of the indurated area should be 
reported as the DTH response.  
 
The measured DTH response must be between ≥ 5 mm and ≤ 25 mm in diameter to be considered a valid 
reaction.  Responses <5 mm or >25 mm would exclude the subject from the study. 
 
8 EFFICACY EVALUATIONS 
8.1 Common Wart Evaluations 
In cohort 1 and 2, the largest common wart located on hands, feet (excluding soles), limbs and/or trunk will 
be selected as the primary injected wart.  
 
In cohort 3, the largest common wart per anatomical region (left or right; arm, hand, leg, foot (excluding 
sole) or the torso) will be selected as the primary injected wart for a maximum of four warts. For cohort 3, 
each injected wart must be located on a different anatomical region. Flat, plantar, facial, periungual, or 
genital warts or warts in region of pre-existing inflammatory condition are excluded.  
8.1.1 Common wart measurement  
The visually largest six common warts (including the primary injectable wart(s)) that can be readily identified 
will be measured at Baseline Visit (V3) and during the study (referred as “measured warts”). Unless the 
wart location can be easily identified in writing using anatomical terms, these (up to 6) largest common 
injectable warts will be mapped on transparencies or drawn in the medical chart to ensure it is accurately 
found at every visit. The mapping process on transparencies will be described in the Study Manual. 
 
Each measured wart will be documented in the source document and reported on the eCRF, with its size, 
age, treatment history and location. Size will be determined by measuring in mm the longest and orthogonal 
diameters of the wart using a ruler. 
8.1.2 Evaluation of primary injected wart status 
The size and status (resolved, partially resolved, or no response) of each primary injected wart will be 
documented at each visit.  Complete resolution of a wart is the absence of visual or measurable presence 

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of verruca vulgaris. Complete resolution of all common warts is the absence of any common warts (i.e. wart 
count = 0).  
 
8.1.3 Evaluation of presence or absence of common warts other than the 
measured common warts  
 
 
  
 
New warts (those not noted at Baseline Visit (V3)) can be recorded in Progress Notes at any given visit, 
but are not tracked except as noted in Section 8.1.4.  If the investigator notes an occurrence of new warts 
that is considered clinically abnormal or unusual, note as an Adverse Event. 
8.1.4 Presence or absence of common warts in designated anatomical areas 
At the Baseline Visit (V3) the presence or absence of common warts in the following anatomical areas will 
be assessed: left arm, right arm, left hand, right hand, left leg, right leg, left foot (excluding sole), right foot 
(excluding sole) and torso. The presence or absence of common wart in these anatomical areas will also 
be assessed at Injection Visit V7, Efficacy Evaluation Visit (V13) and Follow-up Visit (V15).  
 
New common warts in anatomical areas will be defined as the presence of common warts at V7, V13 and/or 
V15 in anatomical area(s) where NO common warts in that anatomic area were present at Baseline 
Visit (V3).  New warts in areas that previously were noted to have warts should not be recorded as such in 
this examination (see Section 8.13).   
9 SAFETY EVALUATIONS 
Investigators are responsible for monitoring the safety of subjects who are participating in this study and for 
alerting the Sponsor of any observation that seems unusual, even if this observation may be considered an 
unanticipated benefit to the subject. The Investigator is responsible for appropriate medical care of subjects 
during the study. 
 
Safety will be evaluated by collecting AEs and clinically significant changes in safety laboratories or vital 
signs. The reported AEs will be coded according to Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
 
The number and percentage of subjects with at least one AE will be tabulated. For a given AE, a subject 
will be counted once even if he or she has experienced multiple episodes for that particular AE. The 
occurrence of AEs by MedDRA System Organ Class (SOC) and preferred term and the severity and 
relationship of the AE to the study drug will be summarized using the number and percentage of subjects.  

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Study participants will be instructed to contact the Investigator immediately in the event they experience 
any severe sign or symptom, or feel they need to seek medical attention. For this purpose, they will be 
provided with an emergency number (available 24 hours daily, 7 days weekly) to report the event and/or 
seek medical advice and assistance.  
9.2 Adverse Events 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product, without 
regard to the possibility of a causal relationship with this treatment. Lack of drug effect is not an AE in 
clinical trials because the purpose of the clinical trial is to establish drug effect. 
 
Any documented pregnancy will be tracked and followed through outcome. While pregnancy itself is not 
considered an AE or an SAE, any pregnancy complications or elective termination of a pregnancy for 
medical reasons will be recorded as an AE and evaluated as a possible SAE.   
 
Prior to enrollment, study site personnel will note the occurrence and nature of each subject’s medical 
condition(s) in the appropriate section of the source document and eCRF. During the study, site personnel 
will again note any change in the pre-existing condition(s) and the occurrence and nature of any AEs.  
 
CANDIN will be administered in accordance with the US labeled indication for assessment of the subject’s 
DTH response to Candida antigen.  AE collection will begin at the time of the DTH injection (Screening Visit 
1). 
 
CANDIN administered intralesionally is the investigational product in this study. Treatment-Emergent AEs 
(TEAEs) will be those arising after the first intralesional wart(s) injection.  
 
If a subject experiences an AE after the informed consent document is signed, but before CANDIN is 

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administered for assessment of the DTH response, the event will be recorded as a non-treatment emergent 
AE in the source document.  If the subject is randomized, the non-treatment emergent event will also be 
captured in the eCRF. If the subject screen fails, the event will not be captured in the eCRF or in the clinical 
database.  
 
AEs reported as related to CANDIN administered for assessment of the DTH response will be described in 
the source document and assessed for expectedness and regulatory reportability using the Candin package 
insert.  If the subject is randomized, the AE related to Candin for the DTH assessment will also be captured 
in the eCRF. 
 
Injection site AEs may be captured from either subject diaries or during Treatment and Follow-up Visits.  In 
all cases, causality and severity of injection site TEAEs are assessed by Investigator as described in 
Sections 9.2.1 and 9.2.2, respectively.  
 
All unresolved, at least possibly related AEs and SAEs will be followed until resolution or until the 
Investigator deems the event to be chronic or the event to be stable or until the subject is lost to follow-up.  
 
For subjects randomized to receive study drug, all AEs and SAEs will be described in the source documents 
and in the eCRF. 
 
Abnormal laboratory values or test results should not be reported as AEs. The criteria for determining 
whether an abnormal objective test finding should be reported as an AE include the following: 
 
 
Test result is associated with accompanying symptoms; 
 
Test result requires additional diagnostic testing or medical/surgical intervention;  
 
Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy; 
 
Test result is considered to be an AE by the Investigator or Sponsor. 
 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute an 
AE.  Any abnormal test result that is determined to be an error does not require reporting as an AE.  
9.2.1 Adverse Events Causality 
The Investigator will establish causality of the AE to experimental treatment. The Investigator should take 
into account the subject’s history, most recent physical examination findings, and concomitant medications.  
 
The following definitions will be used to determine causality of an AE:  
 
- 
Not related: temporal relationship of the onset of the AE, relative to the experimental treatment is 
not reasonable or another cause can explain the occurrence of the AE. 
 
- 
Unlikely related: temporal relationship of the onset of the AE, relative to the experimental treatment 
is reasonable; however, an alternative explanation is more likely. 
 
- 
Possibly related: temporal relationship of the onset of the AE, relative to experimental treatment is 
reasonable; however, follows no known response pattern to the treatment, and an alternative cause 
seems more likely or there is sufficient uncertainty about the cause of the event. 

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- 
Probably related: temporal relationship of the onset of the AE, relative to the experimental treatment 
is reasonable, and follows a known response pattern to the treatment, but a potential alternative 
cause may be present.  
 
- 
Related: temporal relationship of the onset of the AE, relative to the experimental treatment is 
reasonable, follows a known response pattern to the treatment, and an alternative cause is unlikely. 
9.2.2 Adverse Events Severity 
The intensity of an AE is an estimate of the relative severity of the event made by the Investigator based 
on his or her clinical experience and familiarity with the literature. The severity of AEs at the injection site 
will be estimated using the table below from the FDA Guidance for Industry: Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (see below).20 
The following definitions are to be used to rate the severity of AEs that are not at the injection site: 
 
- 
Mild: The symptom is barely noticeable to the subject and does not influence performance of daily 
activities. Treatment is not ordinarily indicated. 
 
- 
Moderate: The symptom is sufficiently severe to make the subject uncomfortable, and performance 
of daily activities is influenced. Treatment may be necessary. 
 
- 
Severe: The symptom causes severe discomfort, and daily activities are significantly impaired or 
prevented. Treatment may be necessary.  Note-severe intensity of an AE such as injection site pain 
does not necessarily mean that it is a SAE (see Section 9.3) 
 
The following definitions from the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials will be used to rate the severity of 
an injection site AE. 
 
Local Reaction to 
Injection 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening (Grade 4) 
Pain 
Does not interfere with 
activity 
Repeated use of non-
narcotic pain reliever 
>24 h or interferes with 
normal daily activity 
Any use of narcotic 
pain reliever by 
physician or prevents 
normal daily activity 
Emergency room visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant discomfort 
at rest 
Emergency room visit or 
hospitalization 
Erythema/Redness* 
2.5 – 5 cm 
5.1—10 cm 
>10 cm 
Necrosis or severe 
exfoliative dermatitis 
Induration/Swelling ** 
2.5 – 5 cm and does 
not interfere with 
normal daily activity 
5.1—10 cm or 
interferes with normal 
daily activity 
>10 cm or prevents 
normal daily activity 
Necrosis  
*In addition to grading the measure local reaction at the greatest single diameter, the measurement should be recorded as a continuous variable. 
**Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
9.3 Serious Adverse Events 
If a subject experiences a SAE after the informed consent document is signed, but before CANDIN is 
administered for assessment of the DTH response, the event will be recorded as a non-treatment emergent 
SAE in the source document. If the subject is randomized, the non-treatment emergent SAE will also be 
captured in the source and reported in the CRF. If the subject screen fails, the SAE will not be reported in 

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the eCRF.  
 
CANDIN will be administered in accordance with the US labeled indication for assessment of the subject’s 
DTH response to Candida antigen. SAEs reported as related to Candin administered for the DTH 
assessment will be described in the source document and assessed for expectedness and regulatory 
reportability using the Candin package insert.  If the subject is randomized, the SAE related to Candin 
administered for the DTH assessment will also be captured in the eCRF. 
 
All SAEs occurring following wart injections and up to 30 days following the last wart injection will be 
captured in the source document and reported in the CRF. 
 
A SAE (event/experience) or reaction is any untoward medical occurrence that at any dose: 
 
 
results in death, 
 
is life-threatening, 
 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the subject was 
at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe. 
 
 
requires in-subject hospitalization or prolongation of existing hospitalization, 
 
results in persistent or significant disability/incapacity, or 
 
is a congenital anomaly/birth defect. 
 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate 
in other situations, such as important medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the 
other outcomes listed in the definition above. These should also usually be considered serious. 
 
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 hospitalization; or development of drug 
dependency or drug abuse. 
9.3.1 SAE Reporting: 
Any SAE, related or not, occurring during the study as described above must be reported as soon as 
possible using the SAE form provided and followed by fax within 24 hours of awareness to: 
 
For each SAE received, the Sponsor will make a determination as to whether the criteria for expedited 
reporting to relevant regulatory authorities have been met. The Sponsor will manage the expedited 

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reporting of relevant safety information to concerned health authorities and competent authorities in 
accordance with local laws and regulations.  
 
The Sponsor will assess the expectedness of each SAE to the study treatment. The current Investigator’s 
Brochure will be used as the reference document to assess expectedness of the event to study drug. 
9.4 Pregnancy Reporting 
If a female subject or if a female partner of a male subject becomes pregnant during the study, the subject 
should inform the study site as soon as possible. No additional treatments shall be administered until a 
serum pregnancy test is performed and confirmed. Upon confirmation of the pregnancy, the female subject 
will be discontinued from the treatment portion of the study, and requested to continue with the follow-up 
visits. Any confirmed pregnancy will be tracked and followed through outcome. While pregnancy itself is 
not considered an AE or an SAE, any pregnancy complications or elective termination of a pregnancy for 
medical reasons will be recorded as an AE and evaluated as a possible SAE. All pregnancies should be 
reported to the Sponsor and Ethics Committee.  
9.6 Laboratory Tests  
All laboratory tests procedures will be referenced in the Central Laboratory Manual. 
9.6.1 Pregnancy Test 
A urine and serum pregnancy test will be performed at the first Screening Visit (V1) for females of 
childbearing potential. Samples will be sent to a central laboratory. Pregnancy testing not required for 
women of non-childbearing potential defined as post-menopausal for at least 2 years or surgically sterile 
(tubal ligation, oophorectomy, or hysterectomy). 
 
A urine pregnancy test will be performed at the DTH challenge if performed at an additional visit after 
Screening Visit (V1), at Baseline Visit (V3) and at every other visit during the injection period (Visits 5, 7, 9, 
11) and Efficacy Evaluation Visit (V13) at the investigative site for all females of childbearing potential. Urine 
pregnancy testing not required for women of non-childbearing potential defined as post-menopausal for at 
least 2 years or surgically sterile (tubal ligation, oophorectomy, or hysterectomy). 

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9.6.2 Clinical Chemistry Analysis 
The following clinical chemistry analyses will be performed at the first Screening and Efficacy Evaluation 
 
 
 
9.6.3 Clinical Haematology Analysis 
A complete blood count
 
 will be performed at the Screening and Efficacy Evaluation Visits (Visits 
1 and 13). Samples will be sent to a central laboratory for analysis and reporting. 
9.6.4 Urinalysis 
Routine urinalysis including blood (
 
 will be performed at the Screening and Efficacy 
Evaluation Visits (Visits 1 and 13). Samples will be sent to a central laboratory for analysis and reporting. 
 
The following microscopic analysis will be performed when relevant for any positive results:
 
 
 
 
 
 
 
 
9.7 Stopping Rules 
The following are Stopping Rules that will be applied to individual subjects or treatment cohorts. In addition 
to the Stopping Rules, the Investigator may discontinue treatment of any subject in which additional 
treatments are judged to be unsafe or intolerable.   
9.7.1 Individual Stopping Rules 
9.7.1.1 Immediate Reactions Following DTH or Intralesional Injection 
Subjects will remain in the clinic for safety monitoring after DTH or intralesional injection for a minimum of 
30 minutes after dosing in the event they experience signs and/or symptoms of immediate hypersensitivity 
and/or anaphylaxis. 
 
 
 
 
  
 
 
 
 
 

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9.7.1.2 Local Reactions 
The following reactions occurring within 7 days following the injection of Investigational Product, as judged 
by the Investigator based upon the subject diary entries, discussion with subject, and the scale in Protocol 
Section 9.2.2, also judged by Investigator as possibly, probably, or definitely related to the Study Drug: 
 
 
Pain  (Severity Grade 4) 
 
Tenderness (Severity Grade 4) 
 
Erythema/Redness  (Severity Grade 4) 
 
Induration/Swelling (Severity Grades 3-4) 
 
If a subject fails to contact the Investigator about the occurrence of a severity Grade 4 local reaction, the 
Investigator and Medical and Safety Monitor will investigate this event to characterize the severity and 
grade of the event, before recommending the stopping of the subject.  
9.7.1.3 Serious Adverse Events (SAE) 
A serious adverse event as defined in Protocol Section 9.3 and is judged as possibly, probably, or definitely 
related to Study Drug. 
 
Additionally, important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they may 
jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes 

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9.7.2.3 Serious Adverse Events (SAE) 
A serious adverse event as defined in Protocol Section 9.3 and is judged as possibly, probably, or definitely 
related to Study Drug. 
 
Additionally, important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they may 
jeopardize the Subject and may require medical or surgical intervention to prevent one of the outcomes 
listed in 9.3. 
10 DATA QUALITY ASSURANCE/SITE MONITORING 
During the study, monitoring visits will be conducted at regular intervals as detailed in the Monitoring Plan. 
The monitoring visits will be conducted to ensure protocol adherence, quality of data, accuracy of entries 
on the eCRFs, drug accountability, compliance with regulatory requirements and continued adequacy of 
the investigational site and its facilities.  
 
The site may be audited and/or monitored by a quality assurance officer named by the Sponsor and/or 
regulatory authorities may wish to perform on-site audits. The Investigator will be given notice before an 
audit occurs and will be expected to cooperate with any audit, provide assistance and documentation 
(including source data) as requested. 
11 DATA COLLECTION AND RETENTION 
Subject data will be entered in the eCRFs by site personnel. The Data Management Plan (DMP) will define 
and document the processes and procedures used to ensure consistent, efficient and effective data 
collection, transfer, storage, quality, and reporting for the study. 
 
The Investigator will maintain source documents for each subject in the study, consisting of case and visit 
notes (clinical medical records) containing demographic and medical information and the results for any 
tests or assessments. All information on the eCRFs must be traceable to these source documents in the 
subject’s file. Data not requiring a written or electronic record will be defined before study start and will be 
recorded directly on the eCRFs, which will be documented as being the source data. 
 
The data collected will be encoded and stored electronically in a database system. AEs will be coded using 
MedDRA and summarized by SOC, Preferred Term, and treatment group.  Summaries by severity and by 
relationship to study drug will also be included.  SAE and discontinuations due to AE will be summarized 
separately. Concomitant medications will be coded using the World Health Organization Drug Dictionary 

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12 CONFIDENTIALITY OF TRIAL DOCUMENTS AND 
SUBJECT RECORDS  
The Investigator must assure that the subjects’ anonymity will be maintained and that their identities are 
protected from unauthorized parties. On eCRFs or other documents submitted to the Sponsor, subjects 
should not be identified by their names, but by an identification code. The Investigator should keep a subject 
enrolment log relating codes with the names of subjects. The Investigator should maintain documents not 
for submission to Sponsor e.g., subjects’ written consent forms, in strict confidence. 
13 INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS 
The Investigator must maintain adequate and accurate records to enable the conduct of the study to be 
fully documented and the study data to be subsequently verified. These documents should be classified 
into two different separate categories: Investigator Study File and Subject Clinical Source Documents. 
 
The Investigator must keep these two categories of documents on file according to country-specific 
regulation, but no less than US FDA requirements, after completion or discontinuation of the study. After 
that period of time, the Sponsor will be contacted for long term disposition (Sponsor storage or disposal).  
14.2 Analysis Populations 
Three populations will be used for the summaries and analyses of the study data.  These populations are 
defined as follows: 
Intent-to-Treat (ITT):  The ITT Population will consist of all randomized subjects who receive at least 
one intralesional dose of study medication. 

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14.3 Subject Disposition 
Subject disposition will be summarized by treatment and overall for the Randomized Population.  
14.4 Demographic and Baseline Characteristic 
Demographic and relevant baseline characteristics will be presented and summarized descriptively by 
cohort/treatment for the ITT 
 Populations.  Additional summary of demographic and baseline 
characteristics may be specified in the SAP, if deemed necessary. 
14.5 Statistical Analysis 
General Considerations 
Baseline:  Baseline refers to the last measurement collected prior to the first dose of randomized study 
medication at Visit 3 (Day 1). 
Placebo:  The placebo data from the three cohorts will be assessed for comparability.  If the data appear 
comparable they will be pooled into one placebo group for analyses.  
Significance Testing:  All statistical testing will be conducted at an α=0.05 significance level.  There will 
be no adjustment of the significance level for multiple comparisons. 
14.5.1 Efficacy analysis 
14.5.1.1 
Analysis of the Primary Efficacy Endpoint 
The primary efficacy endpoint is the number and proportion of subjects with the primary injected wart(s) 
with complete resolution, which will be compared among all treatment groups by using the Cochran-Mantel-
Haenszel test with a stratification factor of single versus multiple anatomical regions.  Each active treatment 
will be compared with the pooled placebo in a similar manner.    

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14.5.2 Safety Analysis 
The analysis of safety data will be performed for the ITT Population unless otherwise stated.  The primary 
safety endpoint is the incidence of TEAEs defined as any new AEs or existing AEs that have worsened 
during or following the first wart(s) injection with CANDIN (Visit 3) through final Follow-up Visit (V15) or 
Early Termination/Withdrawal.  Other safety endpoints include vital signs, physical exams and laboratory 
measures. 

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14.5.2.1 
Analysis of Adverse Events 
TEAEs (those arising after the first intralesional wart injection in this study) will be summarized by treatment, 
SOC, and preferred term defined by MedDRA.  The number of events and number of events by severity, 
the number of subjects, and the percent of subjects who experienced at least one TEAE will be presented 
for each SOC and for each preferred term by treatment group.  TEAEs that lead to early withdrawals and 
serious TEAEs will be summarized in the same manner.  Additional details will be provided in the SAP.  
Injection site TEAEs will be analysed separately from other TEAEs. 
 
DTH-related AEs will be analysed separately by Sponsor and Medical Monitor to determine FDA 
reportability. 
14.5.2.2 
Analysis of Laboratory Measures 
All laboratory results will be listed by treatment, subject, and visit, including scheduled and unscheduled 
measurements.  Laboratory assessments that are outside of normal ranges will be flagged. 
 
Baseline values, the values at each visit, and changes from baseline values will be summarized for each 
of the quantitative laboratory assessments by treatment. 
 
Shift tables of laboratory results will be used to summarize changes from Baseline to the end of the Follow 
up Visit (V15) or Early Termination. 
14.5.2.3 
Analysis of Vital Signs and Physical Examinations 
Vital signs at Baseline (Visit 3, Day 1), each scheduled visit, and changes from baseline values will be 
summarized by treatment. Physical exam findings will be listed. 
15 ETHICS 
15.1 Local Regulations/Declaration of Helsinki 
This study will be conducted in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki (2013) and that are consistent with “Good Clinical Practice” ICH Tripartite Guideline (July 2002) 
and the applicable laws and regulations of the country in which the research is conducted, whichever affords 
the greater protection to the individual.  

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15.2 Ethical Review  
This protocol (and any amendment) as well as appropriate consent procedures and related documents 
(advertisement, subjects’ cards, etc.), will be reviewed and approved by the REB/IRB. This Board must 
operate in accordance with the current Federal regulations. A letter or certification of approval will be sent 
by the Investigator to the Sponsor prior to initiation of the study, and also whenever subsequent 
modifications to the protocol are made.  
15.3 Informed Consent  
It is the responsibility of the Investigator, or a person designated by the Investigator (if acceptable by local 
regulation), to obtain written informed consent from each individual participating in this study after adequate 
explanation of the aims, methods, objectives and potential hazards of the study. It must also be explained 
to the subjects that they are completely free to refuse to enter the study or to withdraw from it at any time 
for any reason.  
 
If new safety information results in significant changes in the risk/benefice assessment or any new 
information that may affect willingness to continue to participate, the consent form should if necessary be 
updated by the Sponsor or Sponsor’s representative and be reviewed by the REB/IRB. All subjects 
(including those already being treated) should be informed of the new information, given a copy of the 
revised form and asked to give their consent to continue in the study. 

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18 APPENDIX A 
 Study Flow Chart 
 
Screening 
Visits 
Baseline 
Visit  
(Day 1) 
Injections Visits2 
Efficacy 
Evaluation 
Visit10 
Follow-up 
Visits 
Visit 
V114 
V21 
V31 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V1314 
V14 
V15 
Window (days) 
-30d 
to -2d 
±4h5  
 
± 2d 
± 3d 
± 3d 
± 7d 
PROCEDURES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Surgical 
History 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Draw for Safety 
Labs14 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Pregnancy Test3 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Vital Signs (Includes weight 
and height at screening) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical Examination  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Full Body Dermatologic 
Examination to identify the 
presence of any wart type  
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Presence or absence of 
common warts in 
designated anatomical 
areas 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Evaluation of presence or 
absence of common warts 
other than the measured 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
X 

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Screening 
Visits 
Baseline 
Visit  
(Day 1) 
Injections Visits2 
Efficacy 
Evaluation 
Visit10 
Follow-up 
Visits 
Visit 
V114 
V21 
V31 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V1314 
V14 
V15 
Window (days) 
-30d 
to -2d 
±4h5  
 
± 2d 
± 3d 
± 3d 
± 7d 
and mapped injectable 
common warts  
Common warts 
measurement and mapping 
(up to 6 injectable common 
warts including all primary 
injectable warts) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Evaluation of primary 
injected wart(s) status 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Selection of primary 
injectable wart(s)9 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Selection and Mapping of 
non-primary  common 
wart(s) for injection8 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
DTH Challenge Injection 
(30-min observation period) 
X13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DTH Evaluation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Draw for Biomarkers 
Evaluation 
X6 
 
 
 
X6, 12 
 
 
 
 
 
 
 
X6 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Intralesional Injection 
(30-min observation period) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Give Subject Diary/Device 
X7 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Review/Retrieve Subject 
Diary 
 
X7 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Retain Diary Device 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Medical Photographs4 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
X 
X 

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Screening 
Visits 
Baseline 
Visit  
(Day 1) 
Injections Visits2 
Efficacy 
Evaluation 
Visit10 
Follow-up 
Visits 
Visit 
V114 
V21 
V31 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V1314 
V14 
V15 
Window (days) 
-30d 
to -2d 
±4h5  
 
± 2d 
± 3d 
± 3d 
± 7d 
Hypopigmentation and 
Scarring Assessments11 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X