Clinical trial NCT04308395
Conditions: Basal Cell Nevus Syndrome
Keywords: Gorlin syndrome Patidegib Basal cell nevus syndrome Nevoid basal cell carcinoma syndrome Basal cell carcinoma Hedgehog Surgically eligible basal cell carcinomas BCC BCNS
Sponsor: Sol-Gel Technologies, Ltd.
Start date: 2020-06-03; Completion date: 2021-07-14
Enrollment: 108 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a multicenter, open label extension study evaluating the safety of Patidegib Topical Gel, 2%, applied topically twice daily to the face of adult subjects with Gorlin syndrome.

Detailed description:

Arms: arm 1: Patidegib Topical Gel, 2%
Interventions: intervention 1: Patidegib Topical Gel, 2%
Intervention descriptions: intervention 1: Patidegib Topical Gel, 2%

Protocol documents:
Prot_002.pdf: 
Pelle-926-301E, Protocol, 30Jan2020; Version 2.0 
PROPRIETARY AND CONFIDENTIAL 
Page 1 of 60 
Clinical Study Protocol 
Protocol Pelle-926-301E 
A Phase 3, Multicenter, Open-Label Extension Study of Patidegib Topical Gel, 2% in 
Subjects with Gorlin Syndrome (Basal Cell Nevus Syndrome)  
Development Phase of Study: 3 
Study design: 
Multicenter, Open Label Clinical Study 
IND #: 
125,461 
Eudra CT number: 
2020-000253-27 
Sponsor Representative: 
Sponsor: 
Version: 
Original: 25 November 2019 
Amendment 1: 30 January 2020 
CONFIDENTIAL 
Nothing herein is to be disclosed without prior approval of the sponsor. 
This protocol will be conducted in compliance with procedures outlined in this document, Good 
Clinical Practice (GCP) guidelines and applicable regulatory requirements. This study will not be 
initiated without the approval of the Institutional Review Board (IRB). Any changes to the protocol 
will be approved in writing by the IRB before implementation except where necessary to eliminate 
an immediate harm to the subject. 
PellePharm, Inc. 
NCT04308395




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Principal Investigator Protocol Agreement Page 
I have carefully read the protocol entitled: “A Phase 3, Multicenter, Open-Label Extension Study 
of Patidegib Topical Gel, 2% in Subjects with Gorlin Syndrome (Basal Cell Nevus Syndrome)” 
and, I declare that, as a Principal Investigator, the clinical protocol was subject to critical review 
and is approved by PellePharm, Inc. (PellePharm).  
I agree to conduct this study in compliance with procedures outlined in this document according 
to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, the 
Declaration of Helsinki, and applicable regulatory requirements. This study will not be initiated 
without the approval of the Institutional Review Board (IRB) or Ethics Committee (EC) or 
Research Ethics Board (REB) and the competent authority. 
I understand that any substantial changes to the protocol must be approved in writing by the 
IRB/EC/REB and the competent authority, if applicable, before it can be implemented except 
where necessary to eliminate immediate harm to the subject. I will provide copies of the protocol 
and access to all information furnished by PellePharm to study personnel under my supervision 
and will discuss this material with them to ensure they are fully informed about the study. I 
understand that the study may be terminated or enrollment suspended at any time by PellePharm 
with or without cause, or by me if it becomes necessary to protect the best interests of the subjects. 
 
 
 
Investigator Signature 
 
Date 
 
 
 
Printed Name 
 
 
Institution Name 
 
 
Address 
 
 
City, State/Country Zip or Postal Code 
 
 
Phone Number 


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SYNOPSIS 
Title 
A Phase 3, Multicenter, Open-Label Extension Study of Patidegib Topical 
Gel, 2% in Subjects with Gorlin Syndrome (Basal Cell Nevus Syndrome) 
Short Title 
PATIDEGIB Phase 3 OLE study in subjects with Gorlin syndrome 
Protocol No 
Pelle-926-301E 
Study Regions 
United States (US), UK, Canada, European Union 
Phase of 
Development 
Phase 3 
Objectives 
Primary Objective 
•
To assess the safety and tolerability of Patidegib Topical Gel, 2% in
patients who have completed PellePharm Study Pelle-926-201 or Pelle-
926-301
Secondary Objectives 
•
To assess the efficacy of Patidegib Topical Gel, 2% in patients who
have completed PellePharm Study Pelle-926-201 or Pelle-926-301
Study Design 
This is a multicenter, open label extension study evaluating the safety of 
Patidegib Topical Gel, 2%, applied topically twice daily to the face of adult 
subjects with Gorlin syndrome.  
Number of 
Subjects 
Maximum of about 200 participants (completers from PellePharm Studies 
926-201 or 926-301).
Study 
Population 
Patients with Gorlin syndrome who have completed PellePharm Study 926-
201 or 926-301 
Study 
duration 
The treatment duration is 12 months, with potential extension beyond this 
period. Enrollment will close approximately after the last patient in Study 
926-301 has completed their Study 926-301- related procedures.
Criteria for 
Evaluation 
Screening Visit 
A screening visit is mandatory for all subjects.  Subjects who fail a 
Screening Visit may be rescreened. All eligibility criteria at the Baseline 
visit must also be met at the Screening/Rescreening visit. Additionally, for 
women of child bearing potential (WOCBP) a serum pregnancy test must be 
negative, at the Screening visit.  
Baseline Visit  
Key Inclusion Criteria (Section 7.1 for a complete list) 
1. The subject must have completed PellePharm Study 926-201 or 926-
301.
2. Study Pelle-926-301 subjects must have completed the End of
Treatment Visit in Study 301, prior to the Screening Visit in this study.


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They must also complete all Study 301 related procedures prior to the 
Baseline Visit of this study.  
3. The subject must be willing to abstain from application of a non-study 
topical medication (prescription or over the counter) to facial skin for 
the duration of the trial except as prescribed by the Investigator. 
Moisturizers and emollients are allowed. Subjects will be encouraged to 
use their preferred sunscreen with a sunscreen protection factor (SPF) of 
at least 30 daily on all exposed skin sites.  
4. Female subjects must have a negative pregnancy test (serum pregnancy 
test at Screening Visit, urine pregnancy test at Baseline Visit). For Study 
301 subjects a negative serum pregnancy test result from Study 301 is 
acceptable if the test was done within 7 days of the Screening Visit of 
this study.  
5. If the subject is a woman of child bearing potential (WOCBP), she must 
be willing to use birth control methods which may be considered highly 
effective (Appendix 17.1). Hormonal contraception must be 
supplemented with a barrier method (preferably condom). Birth control 
must start prior to Baseline, continue through the duration of the study, 
and for 30 days after last application of IP 
6. If the subject is a male with a female sex partner who is a WOCBP, the 
subject must be willing to use condoms, even after a vasectomy, starting 
prior to Baseline, through the duration of the study, and for at least 3 
months after the last application of IP. 
7. The subject is willing for all facial BCCs to be evaluated and follow 
treatment recommendations made only by the Investigator.  
8. The subject is willing to forego treatment of facial BCCs with anything 
other than the study IP except when the Investigator believes that delay 
of treatment of a BCC potentially might compromise the health of the 
subject. In such instances, the only other allowed form of treatment is 
surgical. 
Key Exclusion Criteria (Section 7.1 for a complete list) 
1. The subject has used topical treatment to the face or systemic therapies 
that might interfere with the evaluation of the study IP (Section 7.1 for 
details) 
2. The subject has current, recent (within five half lives of the experimental 
drug or if half life not known, within the past 6 months prior to the 
Screening Visit), or planned (while enrolled in this study) participation 
in an experimental drug study (excluding Study 301).  
3. The subject is a WOCBP who is unwilling or unable to comply with 
pregnancy prevention measures.  
4. The subject is pregnant or breastfeeding. 


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Investigational 
Product (IP)  
Patidegib Topical Gel, 2% (w/w). The IP will be applied to the face defined 
as the area extending from the anterior hairline to the jaw line (except the 
eyelids). If the anterior hairline is receding, application of IP to the forehead 
will extend no more than 9 cm above the eyebrow or superior orbital ridge. 
Assessments 
Background and demographic assessments 
Inclusion and exclusion criteria 
Demography 
Medical history 
Prior and concomitant medications 
 
Efficacy 
Count of facial lesions 
Surgery 
Biopsies 
Quality of life assessments 
 
Safety 
Skin tolerability 
Adverse Events 
Physical examinations 
Pregnancy tests  
Genomic 
testing  
There will be no genomic testing in this study. 
Statistical 
methods 
Sample size 
The study is not powered for statistical significance. 
  
Analysis populations  
The primary population for analysis of safety and efficacy will be the safety 
population. This population will comprise all patients who had at least one 
application of study treatment. Subgroup analysis will be done for subjects 
with history of oral or topical HHI in past 6 months – Yes/No.  
 
Methods of analysis 
All analysis will be descriptively summarized. There will be no hypothesis 
testing.   
 
 
 


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TABLE OF CONTENTS 
 
SYNOPSIS ..........................................................................................................................4 
 
TABLE OF CONTENTS ..................................................................................................7 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..............................10 
 
INTRODUCTION............................................................................................................11 
 
STUDY OBJECTIVES ....................................................................................................13 
5.1 
Primary Objective ..................................................................................................13 
5.2 
Secondary Objective ..............................................................................................13 
 
OVERALL STUDY DESIGN AND PLAN ...................................................................14 
6.1 
Contraception and duration of contraception .........................................................14 
6.2 
Benefit-risk Assessment.........................................................................................14 
 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................................16 
7.1 
Inclusion/Exclusion Criteria – Baseline and when applicable, Screening .............16 
7.1.1 Subject Inclusion Criteria ..........................................................................16 
7.1.2 Subject Exclusion Criteria .........................................................................17 
7.2 
Concomitant Medications and Treatments ............................................................18 
7.3 
Study Drug Discontinuation ..................................................................................18 
7.4 
Subject Withdrawal Criteria ..................................................................................18 
7.5 
Study Discontinuation or Termination...................................................................18 
 
STUDY PROCEDURES AND ASSESSMENTS ..........................................................19 
8.1 
Study Procedures ...................................................................................................19 
8.1.1 Informed Consent.......................................................................................19 
8.1.2 Inclusion and Exclusion .............................................................................19 
8.1.3 Randomization ...........................................................................................19 
8.1.4 Demographics ............................................................................................19 
8.1.5 Medical History .........................................................................................20 
8.1.6 Prior and Concomitant Medications ..........................................................20 
8.1.7 IP Application ............................................................................................20 
8.1.8 Compliance ................................................................................................20 
8.1.9 Unscheduled Visit ......................................................................................20 
8.2 
Efficacy Assessments.............................................................................................20 
8.2.1 Biopsy ........................................................................................................21 
8.2.2 Surgery .......................................................................................................21 
8.2.3 Quality of Life Assessments ......................................................................21 
8.3 
Safety Assessments ................................................................................................24 
8.3.1 Dermal Safety and Tolerability Events ......................................................24 


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8.3.2 Physical Examination and Vital Signs .......................................................26 
8.3.3 Pregnancy Tests .........................................................................................26 
 
TREATMENT PLAN ......................................................................................................27 
9.1 
Methods of Assigning Subjects to Treatment Groups ...........................................27 
9.2 
Treatment Compliance ...........................................................................................27 
9.3 
Protocol Deviations ................................................................................................27 
 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT ..............28 
10.1 
Identity of the Investigational Product ...................................................................28 
10.2 
Packaging and Dispensation of Investigational Product ........................................28 
10.3 
Storage and Handling of Investigational Product ..................................................29 
10.4 
Application .............................................................................................................29 
10.5 
Investigational Product Accountability and Disposal ............................................30 
 
SAFETY INSTRUCTIONS AND GUIDANCE ............................................................31 
11.1 
Adverse Events ......................................................................................................31 
11.1.1 Definition of Adverse Event ......................................................................31 
11.1.2 Documenting Adverse Events....................................................................31 
11.1.3 Serious Adverse Events .............................................................................32 
11.1.4 Assessment of Severity ..............................................................................33 
11.1.5 Assessment of Causality ............................................................................33 
11.1.6 Reporting of Serious Adverse Events ........................................................34 
11.1.7 Emergency Contact ....................................................................................34 
11.1.8 Expedited Serious Adverse Event Reports ................................................35 
 
STATISTICS ....................................................................................................................36 
12.1 
Analysis Population ...............................................................................................36 
12.2 
Subject Disposition ................................................................................................36 
12.3 
Demographics and Baseline Characteristics ..........................................................36 
12.4 
Protocol Deviations ................................................................................................36 
12.5 
Compliance ............................................................................................................36 
12.6 
Assessment of Efficacy ..........................................................................................36 
12.6.1 Efficacy Endpoints .....................................................................................36 
12.6.2 Efficacy Analyses ......................................................................................37 
12.6.3 Sample Size Determination........................................................................37 
12.7 
Assessment of Safety .............................................................................................37 
12.7.1 Dermal Safety and Tolerability ..................................................................37 
12.7.2 Adverse Events ..........................................................................................37 
12.7.3 Physical Examination Including Vital Sign Results ..................................38 
12.7.4 Pregnancy Tests .........................................................................................38 


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QUALITY CONTROL AND QUALITY ASSURANCE .............................................39 
13.1 
Study Monitoring ...................................................................................................39 
13.2 
Audits and Inspections ...........................................................................................39 
13.3 
Data Quality Assurance .........................................................................................39 
 
ETHICS AND ADMINISTRATIVE ISSUES ...............................................................41 
14.1 
Ethical Conduct of the Study .................................................................................41 
14.2 
Independent Review Board Review.......................................................................41 
14.3 
Informed Consent...................................................................................................41 
14.4 
Subject Data Protection..........................................................................................41 
14.5 
Financial Disclosure...............................................................................................42 
14.6 
Investigator Obligations .........................................................................................42 
14.7 
Changes to the Protocol .........................................................................................42 
14.8 
Confidentiality .......................................................................................................42 
 
DATA HANDLING AND RECORD KEEPING ..........................................................43 
15.1 
Inspection of Records ............................................................................................43 
15.2 
Retention of Records..............................................................................................43 
15.3 
Electronic Case Report Form Completion .............................................................44 
 
REFERENCES .................................................................................................................45 
 
APPENDICES ..................................................................................................................46 
17.1 
Contraception .........................................................................................................46 
17.2 
Diagnostic Criteria for Gorlin Syndrome ..............................................................47 
17.3 
Patient Reported Outcomes (PRO) Questionnaires ...............................................48 
Appendix 17.3.1 aBCCdex..................................................................................49 
Appendix 17.3.2 DLQI........................................................................................54 
Appendix 17.3.3 EQ-5D-5L ................................................................................57 
 
List of Tables 
Table 1: 
Schedule of Assessments ............................................................................................22 
Table 2: 
Dermal Safety and Tolerability Scales .......................................................................25 
Table 3: 
Excipients of Patidegib Topical Gel, 2% (w/w) .........................................................28 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or 
Specialist Term 
Definition or Explanation 
aBCCdex 
Advanced Basal Cell Carcinoma Index 
AE 
Adverse Event 
BCC 
Basal Cell Carcinoma 
BSA 
Body Surface Area 
CAPA 
Corrective and Preventive Action Plan 
cGMP 
Current Good Manufacturing Practices 
CRO 
Clinical Research Organization 
DLQI 
Dermatology Life Quality Index 
eCRF 
Electronic Case Report Form 
EQ-5D-5L 
EuroQol (Quality of Life) using 5 levels 
FDA 
Food and Drug Administration 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GRAS 
Generally Recognized as Safe 
HF-BCC 
High-frequency Basal Cell Carcinoma 
HH 
Hedgehog 
HHI 
Hedgehog Inhibitor 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IUD 
Intra-uterine device 
IUS 
Intra-uterine system 
MedDRA 
Medical Dictionary for Regulatory Affairs 
MUSE 
Maximum Use Systemic Exposure 
OLE 
Open Label Extension 
PD 
Protocol Deviation 
PDT 
Photodynamic Therapy 
PE 
Physical Examination 
PRO/ePRO 
Patient Reported Outcome/electronic Patient Reported Outcome 
PSCP 
Primary Skin Care Physician 
PTCH 1 
Patched Protein 1 
QA 
Quality Assurance 
SAE 
Serious Adverse Event 
SEB 
Surgically Eligible Basal Cell Carcinoma 
SoA 
Schedule of Assessments 
SAP 
Statisatical Analysis Plan 
SPF 
Sunscreen Protection Factor 
TEAE 
Treatment-Emergent Adverse Event 
US 
United States 
WHO  
World Health Organization 
WOCBP 
Women of Child Bearing Potential 


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INTRODUCTION 
PellePharm, Inc. (PellePharm) is developing a topical formulation of patidegib for the mitigation 
of the disease burden of persistently developing basal cell carcinomas (BCCs) in patients with 
Gorlin syndrome and a high frequency of BCCs (HF-BCC). There are currently no approved 
therapies for Gorlin syndrome or HF-BCC. The continuous development of BCCs, especially on 
the face, can lead to seriously disfiguring scars and functional impairment, resulting in a 
significant decrease in quality of life. It is hoped that, by decreasing the number of surgeries that 
these patients require, their quality of life will be greatly improved.  
Three clinical interventional studies of Patidegib Topical Gel have been completed by 
PellePharm, Inc. while a fourth study is ongoing. The safety of the oral formulation was 
characterized before the topical was advanced to the clinic (Patidegib IB).   
Study Pelle-926-101 was a Phase 1 maximum use systemic exposure (MUSE) study in healthy 
volunteers. 
 
 
 
 
 
  
Study Pelle-926-201 was a Phase 2 double-blind randomized vehicle-controlled study
 
 
 
 
 
 
  
Study Pelle-926-202 was a double-blind, dose escalating, randomized, vehicle-controlled Phase 
2 study 
 
 
 
 
 
 
Patidegib Topical Gel appeared to be effective in the two Phase 2 studies. Additionally, based on 
the limited data from the three studies, Patidegib Topical Gel was found to be safe and tolerable. 
Patidegib Topical Gel is currently being evaluated in Study Pelle-926-301 – a Phase 3 double 
blind randomized vehicle controlled study in patients with Gorlin syndrome. 
 




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STUDY OBJECTIVES  
5.1 
Primary Objective 
The primary objective of the study is to assess the safety and tolerability of Patidegib Topical 
Gel, 2% in patients who have completed PellePharm Study Pelle-926-201 or Pelle-926-301. 
5.2 
Secondary Objective 
The secondary objective of the study is to assess the efficacy of Patidegib Topical Gel, 2% in 
patients who complete PellePharm Study Pelle-926-201 or Pelle-926-301. 


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OVERALL STUDY DESIGN AND PLAN  
This is an open label study offered to all subjects who have completed Study 926-201 or Study 
926-301. All study participants are treated with Patidegib Topical Gel 2% gel. This ensures that 
patients who were randomized to vehicle in the parent study 926-201 or 926-301receive 
Patidegib Topical Gel in the current study.  
Safety and tolerability are the primary objectives of this study and will be evaluated by 
reviewing adverse events, treatment discontinuations and dermal safety and tolerability. The 
number of facial BCCs removed by surgery is considered an appropriate study endpoint as 
surgery has significant morbidity in Gorlin Syndrome (e.g., scarring, functional loss of eyelid, 
nose, ear).  
Study visits will occur at quarterly intervals.  However for WOCBP, study visits will occur 
monthly (Section 6.1 and Table 1) 
6.1 
Contraception and duration of contraception  
Embryo-fetal toxicity was noted in non-clinical studies (Patidegib IB). This study therefore has 
stringent recommendations on the choice of and duration of contraception.  
Highly effective contraception (defined as a failure rate of < 1%) is mandated for women of child 
bearing potential (WOCBP) (HMA CTFG guidelines). For women on oral contraceptives, the 
likelihood of any clinically significant drug-drug interaction of topical patidegib gel is remote 
due to the absence of first pass metabolism as well as the extremely low patidegib systemic 
exposure following topical administration (Patidegib IB). Nevertheless, as a matter of abundant 
caution, it is recommended that hormonal contraception be supplemented with a barrier method.  
The mean half-life (Study 926-101) for patidegib after 2 weeks of dosing was 
 
 (Patidegib IB). Based on the longest observed half-life 
 in this study > 
 of the circulating drug will be gone from the body 
 after the last dose. In women, 
contraception must continue for a minimum 
 after the last application of IP.  
Patidegib is not genotoxic. For males with a WOCBP partner, it is also not anticipated that 
relevant systemic exposures will be obtained in the WOCBP partner. Nevertheless male subjects 
with a WOCBP partner are required to use a condom from prior to application of the IP and 
continue for a minimum of three months (development of spermatozoa) after the last application 
of IP.  
6.2 
Benefit-risk Assessment 
Mitigation of BCCs and SEB tumor burden has so far been limited to avoiding sunlight, advice 
which is followed infrequently by patients at risk of developing sporadic skin tumors. 
Vismodegib, an orally bioavailable HHI has been studied for efficacy vs. BCCs in patients with 
Gorlin syndrome (Tang et al., 2012). In 41 patients followed for a mean of 8 months (range, 1 to 


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15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was 
lower with vismodegib than with placebo 
 But 
because of detrimental class-specific side effects, most patients discontinue oral HHI such as 
vismodegib (John and Schwartz, 2016). Surgery is currently the definitive treatment for BCCs in 
patients with HF-BCC. Surgery has significant morbidity (e.g., scarring, functional loss of 
eyelid, nose, ear). Meanwhile, in Study Pelle-926-201, Patidegib Topical Gel, 2 % has shown 
promise to potentially mitigate tumor burden, without the systemic toxicity of oral HHI in 
patients with Gorlin syndrome.  
The safety evaluation in the two clinical studies of the topical 2% and 4% formulations (Pelle-
926-201, and Pelle-926-202) have shown that patidegib topical gel in repeated QD and BID 
doses appears to be safe and well-tolerated (Patidegib IB). Based on clinical and non-clinical 
studies for the topical product there are no known (expected) adverse events for the topical 
product. Adverse events and dermal safety and tolerability will nevertheless be monitored 
throughout the Phase 3 study. 
Notwithstanding the low systemic bioavailability of Patidegib Topical Gel, 2%,  (Patidegib IB) 
the class effects seen with oral HHI are considered potential adverse events for Patidegib Topical 
Gel, 2%. These include muscle spasm, alopecia and dysgeusia (Patidegib IB, Lacouture et al., 
2016). As observed with the oral HHI class, embryo-fetal toxicity has been observed in 
nonclinical studies of the oral formulation of patidegib (Patidegib IB). 
In non-clinical studies, changes in growth plate were observed in mice and young dogs treated at 
high doses. In skeletally mature adult dogs, there were no adverse bone changes (Patidegib IB). 
Cessation of growth in children treated with oral HHI has also been reported (Robinson et al., 
2017). Pediatric patients are excluded from this study.  
All formulation components of patidegib topical gel meet standard US or international 
compendial standards and are generally recognized as safe (Patidegib IB). Nevertheless, subjects 
known to have a hypersensitivity to any of the ingredients in the study medication formulation 
are excluded from the study (Section 7.1.2).  
The current benefit-risk profile is therefore deemed acceptable to support the continued 
development of patidegib topical gel in Gorlin patients. 


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SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1 
Inclusion/Exclusion Criteria – Baseline and when applicable, Screening  
A Screening and Baseline visit is mandatory for all subjects. Subjects who fail a Screening visit 
may be rescreened.  
All eligibility criteria at the Baseline visit must also be met at the Screening/Rescreening visit. 
Additionally, at the Screening visit a serum pregnancy test must be negative.  
7.1.1 Subject Inclusion Criteria 
 Subjects meeting all of the following criteria will be eligible for study entry. 
1. 
The subject must be at least 18 years old. 
2. 
The subject must provide written informed consent prior to any study procedures. 
3. 
The subject must have completed PellePharm Study 926-201 or 926-301 with 
adequate compliance 
4. 
Study 926-301 subjects must have completed the End of Treatment Visit in Study 
301, prior to the Screening Visit in this study. They must also complete all Study 301 
related procedures prior to the Baseline Visit of this study. 
5. 
The subject  must meet diagnostic criteria for Gorlin (basal cell nevus) syndrome, 
including major criterion #a plus 1 additional major criterion or plus 2 additional 
minor criteria listed in Appendix 17.2 
6. 
The subject must be willing to abstain from application of a non-study topical 
medication (prescription or over the counter) to facial skin for the duration of the trial 
except as prescribed by the Investigator. Moisturizers and emollients are allowed. 
Subjects will be encouraged to use their preferred sunscreen with a sunscreen 
protection factor (SPF) of at least 30 daily on all exposed skin sites. 
7. 
Female subjects must have a negative pregnancy test (serum pregnancy test at 
Screening Visit, urine pregnancy test at Baseline Visit). For Study 301 subjects, a 
negative serum pregnancy test result from Study 301 is acceptable if the test was done 
within 7 days of the Screening Visit of this study. 
8. 
If the subject is a woman of child bearing potential (WOCBP), she must be willing to 
use birth control methods which may be considered highly effective (Appendix 17.1). 
Hormonal contraception must be supplemented with a barrier method (preferably 
condom). Birth control must start prior to Baseline, continue through the duration of 
the study, and for 30 days after last application of IP 
9. 
If the subject is a male with a female sex partner who is a WOCBP, the subject must 
be willing to use condoms, even after a vasectomy, starting prior to Baseline, through 
the duration of the study, and for at least 3 months after the last application of IP. 
10. 
The subject is willing for all facial BCCs to be evaluated and follow treatment 
recommendations made only by the Investigator.  




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7.2 
Concomitant Medications and Treatments 
All medications listed as exclusion criteria cannot be taken systemically or applied on the face 
concomitantly during the study. This includes the use of drugs indicated for the treatment of 
superficial BCCs such as imiquimod, 5-fluorouracil. Topical agents may be applied on 
anatomical sites other than the face.  
During the study, subjects will be allowed to use moisturizers and emollients and will be 
encouraged to use sunscreen of at least 30 SPF at least once daily on all exposed skin sites. 
Subjects must wait 30 minutes after IP application before applying any moisturizer, emollient, or 
sunscreen.  
BCCs may be removed at the discretion of the Investigator in consultation with the patient, by 
the Investigator or a competent physician/surgeon at any time after the Baseline Visit. 
7.3 
Study Drug Discontinuation 
The Investigator has the right to permanently discontinue IP application of a subject at any time 
if in their opinion the continuation of the IP is deleterious to the subject’s health or 
discontinuation is in the subject’s best interest. If the subject becomes pregnant, IP will be 
discontinued immediately.  
If, for any reason, a subject is discontinued during the treatment period prior to the Exit Visit, 
evaluations should be performed at the time of early termination and the reason for termination 
should be recorded in the end of study source documentation. At the 30 day follow up additional 
information may be collected. All data gathered on the subject will be made available to 
PellePharm. 
7.4 
Subject Withdrawal Criteria 
The Investigator may consider discontinuing a subject with a major protocol violation or 
deviation (e.g., failure to meet study enrollment criteria, use of disallowed medications). 
However, an excessive rate of discontinuation can render the study uninterpretable; therefore, 
unnecessary discontinuation of subjects should be avoided. A protocol violation or deviation 
does not in itself necessarily constitute grounds for removal of the subject from the trial if the 
subject’s safety is not compromised.  
A subject has the right to withdraw from the study at any time for any reason, without prejudice, 
and is under no obligation to disclose the reason. Once a subject has withdrawn from the study, 
no additional information can be collected. All data gathered on the subject prior to withdrawal 
from the study will be made available to PellePharm. 
7.5 
Study Discontinuation or Termination  
The study may be discontinued by PellePharm for medical or ethical reasons affecting the 
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STUDY PROCEDURES AND ASSESSMENTS 
The study will be conducted as outlined in the schedule of assessments (SoA). 
8.1 
Study Procedures  
The SoA is provided in Table 1.  
Study 301 subjects will have their Screening visit after Study 926-301 End of Treatment visit. 
This can be on the same day as the Study 301 End of Treatment visit. Study 301 End of 
Treatment visit assessments may be used for Screening or rescreening assessments in this study 
if the visit in this Study occurs within 7 days of the End of Treatment/Exit visit of Study 301. 
The Baseline Visit may take place no more than 30 days after the Screening/Rescreening visit. If 
this period exceeds 30 days, subjects will need to be re-screened. 
For most patients, following the Baseline Visit, study visits will occur at quarterly intervals. IP 
will be dispensed to cover 3 months supply. However for WOCBP, post Baseline visits will 
occur every month. Only after pregnancy is ruled out at these visits will IP be dispensed.    
Subjects should be seen for all visits on the designated day or as close as practically possible.  
The assessments/procedures to be performed at the different visits are elaborated here. 
8.1.1 Informed Consent 
All subjects must provide written informed consent before any study related procedures are 
performed. Each subject will receive a copy of the signed consent form. Subjects may be pre-
screened (chart review, etc.) for eligibility prior to any study related procedure.  
8.1.2 Inclusion and Exclusion 
Following provision of informed consent from each subject, the Investigator will determine 
whether subjects meet the inclusion/exclusion criteria.  
The study has stringent recommendations on the choice of and duration of contraception. The 
rationale for this is provided in Section 6.1, acceptable contraceptive measures and their duration 
are provided in the inclusion and exclusion criteria and in Appendix 17.1. 
8.1.3 Randomization  
This is an open label study. Subjects will not be randomized. All subjects will receive Patidegib 
Topical Gel. 
8.1.4 Demographics 
Subject's date of birth, gender at birth, race and ethnicity will be recorded in the eCRF. 


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8.1.5 Medical History 
Subjects’ relevant family history and medical history including that pertinent to eligibility 
criteria will be collected. Information about medical conditions that resolved 2 or more years 
prior to Screening do not need to be recorded unless considered relevant by the Investigator. 
8.1.6 Prior and Concomitant Medications 
Prior and concomitant medications will be captured separately for BCC (facial) and other 
indications.  
All medications ongoing in the 12 months prior to Baseline or ongoing at any time during the 
study will be recorded in the eCRF. The start date for all medications that were started during the 
study period must be reported. Likewise, the end date for all medications that were discontinued 
during the study period must be captured. 
8.1.7 IP Application  
For the first application, the subject will apply the IP at the study site under the direction of the 
Study Coordinator (or designee). The IP should be applied after all clinical assessments. 
Additional information on IP application is available in Section 10.4. 
8.1.8 Compliance  
Patients will be dispensed a diary to maintain a log of their IP application. 
8.1.9 Unscheduled Visit  
Subjects may return to the site for unscheduled visits in the event of an AE, SAE or as deemed 
necessary by the Investigator. The same procedures as described in the post-Baseline Visits may 
be conducted. For other subject care management, the Investigator may refer the subject to their 
primary care physician and/or their PSCP. Data collected will be reported in the ‘Unscheduled 
Visit’ eCRF page. 
8.2 
Efficacy Assessments 
At the Baseline visit, the number of lesions on the face that are suspicious for BCC will be 
recorded. Additionally, the number of lesions on the face that are suspicious for BCC and that 
the patient consents to have removed in accordance with PI recommendation will also be 
recorded. These will be removed prior to the next Post-baseline quarterly visit.  
At all quarterly visits,  the number of lesions on the face that are suspicious for BCC will be 
recorded. Additionally, the number of lesions on the face that were suspicious for BCC and 
removed since the last visit will be recorded. Finally the number of lesions on the face that were 
suspicious for BCC, removed and confirmed on histology to be BCC will be recorded. 
The count of facial lesions will exclude lesions on the face where IP should not be applied (i.e 
eyelids). Face is defined as in Section 10.4.  


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8.2.1 Biopsy 
This is a mandated study procedure for all lesions suspicious for BCCs that were removed 
(irrespective of the treatment modality). All biopsies need to be reviewed and reported by a 
licensed physician with appropriate experience. The biopsy diagnosis will be captured in the 
eCRF. The detailed report of the biopsy will be part of the source document. 
8.2.2 Surgery 
During the study, only lesions that the patient consents to have removed in accordance with the 
PI recommendation will be removed.  
Per local standard of care, the PI may decide to biopsy the lesion first and remove it based on 
histopahtologiuc confirmation. Alternately, this may be a one step procedure where the lesion is 
removed and biopsied at the same time.  
8.2.3 Quality of Life Assessments 
Patient reported outcome (PRO) or electronic PRO (ePRO) will be collected 
 
 
 
 
  
 
  
 
 




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f 
Physical examinations will include collection of vital signs and weight (and height at Baseline only). Additional PEs may be collected according to any signs/symptoms and/or positive 
findings at previous PE. 
g 
Serum pregnancy test at Screening and End of treatment/Exit Visit. For Study 301 subjects a negative serum pregnancy test result from Study 301 is acceptable if the test was done within 
7 days of the Screening Visit of this study. Urine pregnancy test at all other visits.   
h 
Efficacy assessments include – number of lesions removed by surgery since last assessment and count of BCCs. Lesions may be removed at any time per PI convenience but before the 
subsequent visit. Lesions identified at the End of treatment/Exit Visit, must be removed within 15 days of this visit.  
i 
AEs that occurred after signing of the informed consent will be recorded.  
j 
Subjects will be trained on how to appropriately apply IP and comply with study procedures. Additional reminders may be provided at subsequent visits, as appropriate.   
k     IP is administered after all other assessments are completed and is followed by a 30-minute observation period. 
l 
All IP tubes (used, partially used, and/or unused) will be returned and weighed. The weight will be recorded on the appropriate eCRF. 
 
 
 


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8.3 
Safety Assessments 
The safety assessments in the study include vital signs, AEs and dermal safety assessments 
(Section 11.1) 
8.3.1 Dermal Safety and Tolerability Events 
Safety and tolerability will be evaluated through assessment of selected local signs and 
symptoms (pain/burning, pruritus, erythema, edema, and crusting) on the face. These 
assessments will be performed prior to the application of IP. Any local skin reaction that requires 
use of a concomitant therapy or causes interruption or discontinuation of the IP should be 
reported as a safety event. These events will be assessed for severity, relative to the skin 
reactions scale (Table 2). 




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8.3.2 Physical Examination and Vital Signs 
Physical examinations (PEs) including vital signs (blood pressure, heart rate, respiration rate, and 
temperature), weight will be collected and reported. Height will be collected at the Baseline Visit 
only. Clinically significant changes from Baseline will be captured as AEs. Changes in BCC 
count will be captured separately as efficacy assessments and not as a PE assessment. Changes in 
BCC count or size will not constitute AEs. 
8.3.3 Pregnancy Tests 
All WOCBP will have a pregnancy test done at all visits, as per the SoA (Table 1). If the 
WOCBP becomes pregnant during the course of the study, she must immediately stop applying 
the IP and report the finding to the Investigator. Potential teratogenicity should be discussed at 
each visit with WOCBP and with male subjects with partners who are WOCBP. 
 
 


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TREATMENT PLAN 
9.1 
Methods of Assigning Subjects to Treatment Groups 
This is an open label study where all patients will receive Patidegib Topical Gel 2%.  
9.2 
Treatment Compliance 
Subjects will be required to return the IP tubes that are used and/or unused. Each subject will be 
instructed on the importance of both the application of the IP and return of the used and unused 
IP tubes. Each tube will be weighed when returned and the results will be entered on the source 
document and eCRF. 
Patients will be dispensed a diary to maintain a log of their IP application. Any interruptions in 
the schedule of IP administration or use of prohibited concomitant medication will be recorded in 
the eCRFs. 
9.3 
Protocol Deviations  
A PD is any change, divergence, or departure from the study design or procedures defined in the 
protocol. Major PDs are a subset of PDs that might significantly affect the completeness, 
accuracy, and/or reliability of the study data or that might significantly affect a subject's rights, 
safety, or well-being (FDA sheets and notices). If a major (important) PD has been identified, it 
should be communicated to and discussed with the Medical Monitor. A corrective and 
preventative action (CAPA) plan may be required to be instituted in the case of major PDs at the 
site. In the event of recurring major PDs, the site enrollment may be halted by the Medical 
Monitor, in consultation with PellePharm, until a CAPA plan has been instituted and the issue(s) 
resolved. PDs should be reported on at least an annual basis to the Central IRB or the site’s local 
IRB. 


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For IP received undamaged, IP will be inventoried and the IP inventory/accountability log 
completed.  
The subject will return all IP gel tubes (used, partially used, and/or unused) at their subsequent 
study visit. If any IP gel tubes are lost or damaged between clinic visits, additional IP may be 
provided to the subject. The goal is to ensure that the subject has an adequate supply of IP to be 
able to administer all scheduled treatments.  
Refer to the Pharmacy Manual for additional details about administration requirements, IP 
supply, and accountability procedures. 
10.3 Storage and Handling of Investigational Product 
The IP tubes should be stored under controlled room temperature at 20-25 °C (68-77 °F) with 
excursions allowed from 15-30 °C. 
10.4 Application 
The IP should be applied to the face, which will be defined as the area extending from the 
anterior hairline to the jaw line (except the eyelids) including the ears. If the anterior hairline is 
receding, application of IP to the forehead will extend no more than 9 cm above the eyebrow or 
superior orbital ridge. 
The initial application of the IP will take place in the clinic under observation. The Investigator 
or site personnel will instruct the subject on how to apply the IP at the Baseline Visit and the 
subject will apply the IP at that visit under observation. The Investigator or site personnel will 
instruct the subject on the proper use of laminated dosing cards during the Baseline Visit. 
Subjects will apply to the face an amount squeezed out as a specified amount on the laminated 
dosing card 
 avoiding the eyelids (as described 
above and in the Pharmacy Manual). If no observable AEs are noted within a 
 
observation period after their first application, subjects can leave the site. No other IP 
applications at subsequent visits will be required to be observed in the clinic setting. 
In addition to the verbal instructions given during the visit, written and/or other media IP 
application instructions may be provided to the subjects. Subjects should be encouraged to keep 
facial hair short enough to allow adequate application of IP to the face, and subjects must remove 
make-up prior to IP application. Make-up should not be applied any sooner than 30 minutes after 
the application of IP. If feasible the application of make-up may be deferred for as long as 
possible. Subjects will be instructed to wash their face and hands within approximately 10 
minutes prior to IP application. Subjects will be advised to minimize exposure to direct sunlight 
and to wash their hands before and after application of the IP. 
 
If an IP application has been missed or delayed such that there would be 
 
between applications, the subject should not apply that dose of IP and just wait to apply the next 


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dose. The importance of IP compliance should be discussed with the subject during each site 
visit.  
Subjects will be instructed to store their IP in a secure location away from children. WOCBP 
should not come in contact with the gel unless using contraception as specified in this protocol. 
If it is suspected that inappropriate amounts of IP are being applied by the subject further review 
of IP application in the clinic may be warranted. 
10.5 Investigational Product Accountability and Disposal 
Upon receipt of the IP, the Investigator (or designee, e.g., study center pharmacist) will 
acknowledge receipt of the IP after reviewing the shipment’s content and condition. The 
Investigator (or designee) is responsible for ensuring that the designated study site staff conduct 
a complete inventory of study materials and assume responsibility for their storage and 
dispensing. The Investigator (or designee) must agree to keep all study materials in a secure 
location with restricted access. The Investigator (or designee) will keep a record of the inventory 
and dispensing of all IPs. This record will be made available to the Study Monitor for the 
purpose of accounting for all clinical supplies. Any significant discrepancy and/or deficiency 
must be recorded with an explanation. 
All supplies sent to the investigators will be accounted for and, in no case, used in any 
unauthorized situation. Each tube of IP administered at the study center will be administered by 
qualified study center staff. At each site visit, IP compliance will be discussed with the subject. 
At the end of the study, following final IP inventory reconciliation by the monitor, the study site 
will dispose of and/or destroy all supplies (including used, partially used, and/or unused tubes of 
IP) where possible, in compliance with the site’s SOPs for IP disposal/destruction. In the event 
that the site is unable to dispose of and/or destroy IP supplies, the Sponsor will be notified and a 
third-party vendor may be contracted to manage destruction of IP supplies.  
Refer to the Pharmacy Manual for additional details about IP accountability procedures, 
including the IP accountability log. 
 


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 SAFETY INSTRUCTIONS AND GUIDANCE 
11.1 Adverse Events 
11.1.1 Definition of Adverse Event 
An AE is any untoward medical occurrence in a subject administered a medicinal product and 
which does not necessarily have a causal relationship with the medicinal (investigational) 
product. AEs include any unfavorable and unintended illness, sign, symptom, clinically 
significant laboratory test abnormality, or disease associated with the use of a medicinal 
(investigational) product that has appeared or worsened during the course of the clinical trial, 
regardless of causal relationship to the medicinal (investigational) product under study.  
Subjects will be questioned about any concurrent illness or sign or symptom. Any incidence of 
these signs or symptoms will be reported on the AE eCRF. 
Vital signs and laboratory abnormalities are to be recorded as AEs only if they are clinically 
significant (for example: are symptomatic, requiring corrective treatment, leading to 
discontinuation or fulfilling a seriousness criterion). A laboratory abnormality that is part of an 
efficacy endpoint (e.g., histologic confirmation of BCC on a biopsy) is not to be reported as an 
AE. 
An unexpected AE is one that is not listed in the Investigator’s Brochure (IB) or is not listed at 
the specificity or severity that has been observed. 
11.1.2 Documenting Adverse Events 
It is the responsibility of the Investigator to document in the eCRF all AEs/SAEs that occur 
during the course of the study. AEs/SAEs should be collected after the informed consent form is 
signed and usually at the Screening visit. The AEs/SAEs should be documented as a single 
medical diagnosis. When this is not possible, the AE/SAEs should be documented in terms of 
signs and/or symptoms observed by the Investigator or reported by the subject at each study visit. 
All AEs/SAEs occurring after the subject signs the informed consent through the last study visit 
must be reported, regardless of whether or not the AEs/SAEs are considered drug-related. All 
AEs/SAEs, whether in response to a query, observed by the study site personnel, or reported 
spontaneously by the subject, will be recorded. 
At each visit during the study, the subject will be assessed for the occurrence of new and ongoing 
AEs. Dermal safety and tolerability assessments that result in the subject requiring a concomitant 
therapy or discontinuation from the study will be reported as an AE/SAE. The following data 
will be collected on all AEs and recorded on the appropriate eCRF: 
• Event name (diagnosis preferred, if unknown, record the signs/symptoms) 
• Onset date and end date 


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• Maximum severity 
• Seriousness 
• Action taken regarding IP 
• Corrective treatment, if given 
• Outcome 
In addition, the Investigator’s assessment of causality will be recorded.  
It is not necessary to capture multiple occurrences of an AE separately if the event recurs at short 
intervals. In such instances the end date of the AE is the date when the event resolved last and 
did not recur. If however the event recurs after long intervals, then the subsequent event may be 
captured as a separate event. The PI may use his/her discretion to determine what constitutes a 
long or short interval between events and which event is reported once versus more than once. 
Protocol defined endpoints (e.g new BCCs on the face, nSEBs on the face and BCC surgeries on 
the face) will be summarized as efficacy parameters and are not to be reported as AEs/SAEs.  
In the clinical database, information pertaining to all AEs including SAEs are to be recorded for 
a minimum up to the 30 day follow up visit. In the source documents, any and all AEs including 
SAEs must be thoroughly documented to conclusion or in the opinion of the investigator, the 
event has resolved or stabilized. 
11.1.3 Serious Adverse Events 
All AEs will be assessed as either serious or non-serious. 
An SAE or serious adverse reaction is defined as any untoward medical occurrence that at any 
dose: 
• Results in death 
• Is immediately life threatening, (the term "life threatening" in the definition of "serious" 
refers to an event in which the subject is 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-patient hospitalization or prolongation of existing hospitalization 
(hospitalization for elective surgery for a condition present at Screening is not considered 
an AE) 
• Results in persistent or significant disability/incapacity (permanent or substantial 
disruption of a person’s ability to conduct normal life functions) 
• Is a congenital anomaly/birth defect 
• Is a medically important event that may not be immediately life threatening or result in 
death or hospitalization, but may jeopardize the subject and may require medical or 
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If the BCC surgery requires, as per standard of care, that the patient be hospitalized, then this 
hospitalization is not an SAE. 
Note: A spontaneous abortion will be considered an SAE and must be reported per Reporting of 
SAEs under Section 11.1.6. Pregnancy in and of itself is not an SAE, but a subject who becomes 
pregnant must discontinue IP application immediately and the pregnancy will be followed to 
term (and ideally the child will be followed afterward if the subject consents) or termination. 
Any birth defect or other serious issue that may arise during the pregnancy or due to fetal 
exposure will be considered an SAE.  
11.1.4 Assessment of Severity 
The severity assigned to an AE should be determined by the maximum severity of the AE. The 
categories described below should be used to estimate the severity of AEs: 
• Mild: Transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required 
• Moderate: Mild to moderate limitation in activity; some assistance may be needed; no or 
minimal medical intervention/therapy required 
• Severe: Marked limitation in activity; some assistance usually required; medical 
intervention/therapy required; hospitalization or prolongation of current hospitalization 
possible; may be incapacitating or life threatening 
11.1.5 Assessment of Causality 
The Investigator should assess the relationship of the AE, if any, to the IP. The following should 
be taken into account when assessing SAE causality: 
• Positive temporal relationship to IP, such as if the IP was discontinued and the SAE 
resolved or the event recurred after re-introduction. 
• If there is a reasonable possibility that the AE is associated with an underlying or 
concomitant illness. 
• Possible association with previous or concomitant therapy. 
• No temporal relationship to the IP and/or a more likely alternative etiology exists. 
• If the AE is directly related to study procedures or a lack of efficacy. 
The following classifications should be used when evaluating the relationship of AEs and SAEs 
to the investigational drug. 
1. Not Related: No relationship between the experience and the administration of IP; 
related to other etiologies such as concomitant medications or subject’s clinical state. 
2. Unlikely: The current state of knowledge indicates that a relationship is unlikely.  
3. Possibly: A reaction that follows a plausible temporal sequence from administration of 
the IP and follows a known response pattern to the suspected IP. The reaction might have 


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been produced by the subject’s clinical state or other modes of therapy administered to 
the subject. 
4. Probably: A reaction that follows a plausible temporal sequence from administration of 
the IP and follows a known response pattern to the suspected IP. The reaction cannot be 
reasonably explained by the known characteristics of the subject’s clinical state or other 
modes of therapy administered to the subject. 
5. Definitely: A reaction that follows a plausible temporal sequence from administration of 
the IP and follows a known response pattern to the suspected IP and can be confirmed 
with a positive re-challenge test or supporting laboratory data. 
11.1.6 Reporting of Serious Adverse Events 
 SAEs will be captured in both the clinical and safety database.  
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e., signs the informed consent) and throughout the duration of the study 
and for 30 days following the last IP application will be captured in the clinical database via the 
eCRFs (Section 11.1.2).  
SAEs also will be captured in the safety database. An initial SAE Report must be completed for 
all SAEs (irrespective of relatedness) with an onset date within 30 days from the date of last IP 
application. An initial SAE Report must also be completed for Related SAEs (possibly, probably 
or definitely) regardless of the time elapsed from the last dose (even if the study has been 
closed). 
When new, significant information for an SAE is obtained, as well as when the outcome of an 
SAE is known, the Investigator must submit a Follow-Up Report. If the subject was hospitalized, 
a copy of the discharge summary must be included as part of the subject’s medical file. For 
related events, the Investigator should monitor the subject until the outcome of the SAE is 
known. This may require periodic Follow-Up Reports. 
PellePharm and the study CRO must be notified of all SAEs (regardless of causal relationship to 
IP) within 24 hours of the Investigator’s knowledge of the event by faxing or emailing a 
completed SAE report to the CRO Medical Monitor.  
If there are serious, unexpected AEs associated with the use of the IP, PellePharm (or designee) 
will notify the appropriate regulatory agency (ies) and all appropriate parties as appropriate (e.g., 
IRB) on an expedited basis. It is the responsibility of the Investigator to promptly notify the IRB 
of all unexpected SAEs involving risk to human subjects. 
11.1.7 Emergency Contact 
In the event of a medical emergency (i.e., an event that requires immediate attention regarding 
the treatment of a subject, operation of the clinical study, and/or the use of investigational drug), 
investigational site personnel should endeavor to contact the Medical Monitor to discuss the 
situation. 


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11.1.8 Expedited Serious Adverse Event Reports 
PellePharm will notify regulatory authorities of unexpected related SAEs and all participating 
study sites in writing for submission by the Investigator to the IRB, EC or REB. This notification 
will be in the form of a Safety Update to the IB (i.e., “15-day letter”). 
Upon receiving such notices, the Investigator must review and retain the notice with the IB and 
immediately submit a copy of this information to the responsible IRB/EC/REB, according to 
local regulations. The Sponsor, Investigator and IRB//EC/REB will determine if the informed 
consent requires revision. The Investigator should also comply with the IRB//EC/REB 
procedures for reporting any other safety information. 


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 STATISTICS 
12.1 Analysis Population 
The primary population for analysis of safety and efficacy will be the Safety population. This 
population will comprise all patients who had at least one application of study treatment. 
Subgroup analysis will be done for subjects with history of oral or topical HHI in past 6 months 
– Yes/No. 
12.2 Subject Disposition 
A tabulation of subject disposition will be provided. The tabulation will include the numbers of 
subjects who enter the study, complete the study, and discontinue the study. The reasons for 
discontinuation will be included. 
12.3 Demographics and Baseline Characteristics 
Subject demographic data and Baseline characteristics will be summarized using descriptive 
statistics for the Safety population.  
12.4 Protocol Deviations 
All PDs will be reported to PellePharm and recorded throughout the study. A tabulation of PDs 
will be included in the final study report. 
12.5 Compliance 
 Compliance will be determined from the use of diary cards.  
12.6 Assessment of Efficacy 
12.6.1 Efficacy Endpoints 
The efficacy endpoints are as follows: 
1. The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 12 
2. The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 6. 
3. The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 12.  
4. The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 6. 
5. Change from Baseline to Month 12 in the total number of facial lesions suspicious for 
BCC   
6. Count of facial lesions suspicious for BCC over time  
7. aBCCdex change in lesion score from Baseline to Month 12 


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12.6.1.1 Exploratory Endpoints 
Additional endpoints will be listed in the Statistical Analysis Plan (SAP). 
12.6.2 Efficacy Analyses 
All analysis will be descriptively summarized. There will be no hypothesis testing. Additional 
information, including the handling of missing data will be provided in the SAP.   
12.6.3 Sample Size Determination 
This study is not powered for efficacy. All eligible subjects from Study 201 and 301 will be 
enrolled into this study.  
12.7 Assessment of Safety 
Safety results will be summarized with means and standard errors, or proportions. Treatment-
emergent AEs (TEAEs) will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA). Previous and Concomitant drugs will be coded using the WHO-Drug dictionary. 
12.7.1 Dermal Safety and Tolerability 
The frequency of dermal safety and tolerability assessments including pain/burning, pruritus, 
erythema, and edema will be summarized descriptively by visit. 
12.7.2 Adverse Events 
Subjects will be assessed for the occurrence of new and ongoing AEs. Listings of AEs will 
include the dates of onset and resolution (if resolved), maximum severity, seriousness, action 
taken regarding the IP, corrective treatment, outcome, and Investigator’s assessment of causality. 
All AEs will be recorded and classified using terminology from the MedDRA. All reported 
TEAEs, defined as any AE with an onset on or after the date of first IP application, or worsening 
of an AE with an onset prior to first IP application, will be summarized, the number of subjects 
reporting TEAEs, system organ class, preferred term, severity, and relationship to IP. When 
summarizing TEAEs by severity or relationship to IP, each subject will be counted only once 
within a system organ class or a preferred term using the event with the greatest severity or 
causality, respectively, within each category. All reported SAEs will be summarized, the number 
of subjects reporting SAEs, system organ class, preferred term, severity, and relationship to IP. 
All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the Investigator, as well as the 
preferred term, system organ class, start date, stop date (if stopped), seriousness, severity, action 
taken regarding the IP, corrective treatment, outcome and relationship to the IP. In addition, a 
listing of subjects who prematurely discontinue from the study due to AEs will be provided as 
well as a listing of subjects who reported an SAE. 


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12.7.3 Physical Examination Including Vital Sign Results 
Changes from Baseline in vital sign measurements will be summarized with descriptive statistics 
at all applicable study visits. 
12.7.4 Pregnancy Tests 
Pregnancy test results will be presented in a data listing. 


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 QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 Study Monitoring 
The Sponsor or designee will be responsible for the monitoring of the study. Study monitors will 
contact and visit the Investigators at regular intervals throughout the study to verify adherence to 
the protocol, and assess the completeness, consistency, and accuracy of the data by comparing 
patients’ medical records with entries in the eCRF. 
The study monitor must be allowed access to laboratory test reports and other patient records 
needed to verify the entries on the eCRF, provided patient confidentiality is maintained in 
accordance with local requirements. These records, and other relevant data, may also bereviewed 
by appropriate qualified personnel independent from the Sponsor or designee, who is appointed 
to audit the study. Patient confidentiality will be maintained at all times. 
By agreeing to participate in this research study, the Investigators agree to co-operate with the 
study monitor to ensure that any problems detected during the monitoring visits are promptly 
resolved. 
13.2 Audits and Inspections 
The study will be conducted under the sponsorship of PellePharm in conformation with all 
appropriate legal regulations, as well as ICH guidelines. Interim and end of study audits of raw 
data, study files, and final report may be conducted by the study CRO and/or PellePharm’s QA 
Department or designee. 
PellePharm is responsible for implementing and maintaining quality assurance and quality 
control systems to ensure that studies are conducted and data are generated, documented, and 
reported in compliance with the protocol, GCP, and applicable regulatory requirements. In 
addition, PellePharm will be responsible for securing agreement from all involved parties to 
ensure direct access to all study sites, source data/documents, eCRFs, and reports for the purpose 
of monitoring and auditing by PellePharm, and inspection by domestic and foreign regulatory 
authorities. 
13.3 Data Quality Assurance 
All assessments performed will be accurately documented in the subject’s source documents and 
eCRFs. The Investigator or designee will enter the information required by the protocol into the 
source documents and eCRFs provided by PellePharm or designee. Subjects will be identified in 
the eCRFs by their assigned subject number only. 
The Investigators must read the protocol thoroughly and must follow the instructions. Any 
deviations should be agreed to by prior discussion between PellePharm and the Investigator, with 
appropriate written protocol amendments made prior to implementing the agreed changes. Any 
amendment containing major modifications (particularly if it may involve an increased risk to 


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the subjects) will be approved by the IRB/EC/REB before it may be implemented. No change in 
the conduct of the study can be instituted without written approval from PellePharm. 
 


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 ETHICS AND ADMINISTRATIVE ISSUES 
14.1 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles originating from the 
Declaration of Helsinki, ICH guidelines, GCP, and in compliance with local regulatory 
requirements. The Investigator agrees, when signing the protocol, to adhere to the instructions 
and procedures described in it and thereby to adhere to the principles of GCP. 
14.2 Independent Review Board Review 
This protocol, proposed informed consent form and other information provided to subjects, and 
all appropriate amendments will be properly reviewed and approved by the IRB/EC/REB. A 
signed and dated notification of the IRB/EC/REB approval will be provided to PellePharm and 
Investigator prior to study initiation. The name and occupation of the chairman and members of 
the IRB/EC/REB will be supplied to PellePharm. The Investigator will provide required progress 
reports and report all SAEs to the IRB/EC/REB as required by the IRB/EC/REB. 
14.3 Informed Consent 
An IRB-approved Informed Consent Form (ICF) that displays the version and date of approval is 
required for completion by signature from each subject prior to conduct of any study procedures 
under this protocol, including Screening tests and evaluations. The ICF, as specified by the 
investigational site’s IRB/EC/REB, must follow the Protection of Human Subjects regulations 
listed in 21 Code of Federal Regulations Part 50.  
The background of the proposed study and the benefits and risks of the procedures and study 
must be clearly and understandably explained to the subjects. It is the responsibility of the 
Investigator to obtain consent and to provide the subject with a copy of the signed and dated ICF. 
Confirmation of a subject’s informed consent must also be documented in the source 
documentation prior to any testing under this protocol, including Screening tests and evaluations. 
All ICFs used in this study must be approved by the appropriate IRB/EC/REB and by the study 
CRO and/or PellePharm or designee. The ICF must not be altered without the prior agreement of 
the relevant IRB/EC/REB and study CRO and/or PellePharm. 
14.4 Subject Data Protection 
Subject data will be protected by ensuring that no captured data contain subject names, 
addresses, telephone numbers, email addresses, or other direct personally identifying 
information. It is acknowledged that subject initials, demographics (including birthdate), medical 
histories, and prior concomitant medication uses, along with the name and address of the 
enrolling investigator may allow for personal identification of study participants. Other than 
where necessary to meet regulatory requirements, all data collected in this study will be 
presented in tabulated (i.e., aggregate) form, and listings containing information that could be 
used to identify an individual subject will not be included in any public disclosures of the study 


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data or the study results. Any individual data listings required to be presented to comply with 
regulatory requirements will be de-identified prior to disclosure. 
14.5 Financial Disclosure 
Financial disclosures will be obtained from all investigators in order to document any potential 
conflicts of interest. 
14.6 Investigator Obligations 
The Investigator agrees, when signing the protocol, to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of GCP. 
14.7 Changes to the Protocol 
The Investigators must read the protocol thoroughly and must follow the instructions. Waivers 
for enrollment should be avoided, and PellePharm does not plan to provide any waivers. Any 
amendment to the protocol containing major modifications will be approved by the IRB before it 
may be implemented. No change in the conduct of the study can be instituted without written 
approval from PellePharm. 
14.8 Confidentiality 
All the data furnished to the Investigator and his/her staff and all data obtained through this 
protocol will be regarded as confidential and proprietary in nature and will not be disclosed to 
any third party, except for the study CRO, FDA or other regulatory body, without written 
consent from PellePharm. 


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 DATA HANDLING AND RECORD KEEPING 
15.1 Inspection of Records 
Investigators must maintain detailed records on all subjects who are enrolled in the study or 
undergo Screening. Data will be recorded in the subject’s source documents and in applicable 
study logs provided by the study CRO and/or PellePharm. Source documents include subject 
medical records, hospital charts, site charts, investigator subject study files, as well as the results 
of diagnostic tests (e.g., laboratory tests). All required data should be recorded in the study 
documentation completely for prompt data review. Upon study completion or at any other time 
specified by the study CRO and/or PellePharm, the appropriate study documents must be 
submitted. 
The Investigator must keep accurate separate records (source documentation) of all subject visits, 
being sure to include all pertinent study related information. At a minimum, this includes the 
following information: 
• A statement indicating that the subject has been enrolled in the study and the subject 
number 
• Date that the ICF was obtained 
• Evidence that the subject meets study eligibility requirements (e.g., medical history, 
Screening evaluations) 
• Dates of all study related visits and results of any evaluations/procedures performed, 
including who performed each assessment at each visit 
• Use of any concurrent medications during the study 
• Documentation of IP accountability 
• Any and all side effects and AEs must be thoroughly documented to conclusion or until 
the event has stabilized in the opinion of the Investigator 
• Results of any diagnostic tests conducted during the study 
• The date the subject exited the study and a statement indicating that the subject 
completed the study or was discontinued early, including the reason for discontinuation 
Notes describing telephone conversations and all electronic mail with the subject, PellePharm, or 
PellePharm’s designee concerning the study must be recorded or kept on file. All source 
documents must be made available to PellePharm and PellePharm’s designated monitor upon 
request. 
15.2 Retention of Records 
The Investigator should properly store and maintain all study records in accordance with 
PellePharm directives. All records relating to the conduct of this study are to be retained by the 
Investigator until notified by PellePharm in writing that the records may be destroyed. 


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The Investigator will allow representatives of PellePharm’s monitoring team, the governing IRB, 
the FDA or other applicable local authorities to inspect all study records, eCRFs, and 
corresponding portions of the subject’s study site and/or hospital medical records at regular 
intervals throughout the study. These inspections are for the purpose of verifying adherence to 
the protocol, completeness and accuracy of the data being entered onto the eCRF, and 
compliance with FDA or other local authority regulations. 
15.3 Electronic Case Report Form Completion 
eCRFs will be completed for each enrolled subject. It is the Investigator’s responsibility to 
ensure the accuracy, completeness, and timeliness of the data reported in the subject’s eCRF. 
Source documentation supporting the eCRF data should indicate the subject’s participation in the 
study and should document the dates and details of study procedures, AEs, and subject status. 
The eCRFs should be completed within 48 hours of the subject visit.  
Investigators will maintain copies of the eCRFs at the investigational site. For subjects who 
discontinue or terminate from the study, the eCRFs will be completed as much as possible, and 
the reason for the discontinuance or termination clearly and concisely specified on the 
appropriate eCRF. 
 


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 REFERENCES 
1. 
Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in 
patients with the basal-cell nevus syndrome. New England Journal of Medicine 
2012;366:2180-8. 
2. 
Patidegib Investigator Brochure (IB). version: Patidegib-19-01. 25 March 2019. 
3. 
Heads of Medicines Agencies (HMA). Clinical Trial Facilitation Group (CTFG). 
https://www.hma.eu/ctfg.html 
4. 
John AM, Schwartz RA. Basal cell naevus syndrome: an update on genetics and 
treatment. Br J Dermatol. 2016 Jan;174(1):68-76. 
5. 
Lacouture ME, Dréno B, Ascierto PA, et al. Characterization and management of 
hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell 
carcinoma. 2016:theoncologist. 2016-0186.  
6. 
Robinson GW, Kaste SC, Chemaitilly W, Bowers DC, Laughton S, Smith A, et al. 
Irreversible growth plate fusions in children with medulloblastoma treated with a targeted 
hedgehog pathway inhibitor. Oncotarget. 2017 Sep 1;8(41):69295-69302. 
7. 
https://www.fda.gov/scienceresearch/specialtopics/runningclinicaltrials/ 
guidancesinformationsheetsandnotices/ucm219488.htm 
8. 
Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with 
nevoid basal cell carcinoma syndrome. American Journal of Medical Genetics 
1997;69:299-308. 


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 APPENDICES 
17.1 Contraception  
1. Definitions 
a. Definition of Childbearing Potential 
For the purposes of this study, a female born subject is considered a woman of childbearing 
potential (WOCBP) after the initiation of puberty following menarche and until becoming post-
menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy.  
Women are considered to be in a post-menopausal state when there has been a cessation of 
previously occurring menses for > 12 months without an alternative medical cause. A high 
follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
post-menopausal state in women not using hormonal contraception or hormonal replacement 
therapy. However, in the absence of 12 months of amenorrhea, a single FSH measure is 
insufficient.  
b. Definition of Male Fertility 
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation. 
2. Contraception Requirements 
a. Contraception Requirements for Female Subjects  
Hormonal contraception must be supplemented with a barrier method (preferably condom).  
Highly effective forms of birth control include (but are not limited to) the following: 
• combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation 1: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD) 
• intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
• vasectomised partner  
• sexual abstinence 


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17.2 Diagnostic Criteria for Gorlin Syndrome 
Diagnostic criteria for Gorlin syndrome includes major criterion #a plus 1 additional major 
criterion or plus 2 additional minor criteria listed below. 
Major criteria: 
a. 
>2 histologically confirmed BCCs or 1 for subjects under age 20. 
b. 
Odontogenic keratocysts of the jaw confirmed histologically. 
c. 
≥3 palmar and/or plantar pits seen at the Screening Visit. 
d. 
Bilamellar calcification of the falx cerebri present at less than 20 years old. 
e. 
Fused, bifid, or markedly splayed ribs. 
f. 
First degree relative with Gorlin Syndrome. 
g. 
PTCH1 mutation predicted to be of functional significance in normal tissue. 
 
Minor criteria: 
a. 
Macrocephaly. 
b. 
Congenital malformations including frontal bossing, cleft lip or palate, “coarse 
face”, moderate to severe hypertelorism. 
c. 
Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus 
deformity, or marked finger syndactyly. 
d. 
Skeletal abnormalities detectable radiographically: bridging of the sella turcica; 
vertebral abnormalities such as hemivertebrae, fusion or elongation of the vertebral 
bodies; modeling defects of the hands and feet; flame shaped lucencies of the hands 
or feet. 
e. 
Ovarian fibroma. 
f. 
Medulloblastoma  
(modification of criteria of V Kimonis et al Am J Med Genet 69: 299-308, 1997) 
 
 


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17.3 Patient Reported Outcomes (PRO) Questionnaires 


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Appendix 17.3.1 
 




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Appendix 17.3.2 
 


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Appendix 17.3.3 
 


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SAP_003.pdf: 
l 
CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
A Phase 3, Multicenter, Open-Label Extension Study of Patidegib 
Topical Gel, 2% in subjects with Gorlin Syndrome (Basal Cell Nevus 
Syndrome) 
Sponsor Study Code: Pelle-926-301E 
TFS Project Code:
Sponsor 
PellePharm, Inc. 
Product/Compound/Device 
Patidegib 
Phase of the study 
III 
EudraCT number 
2018-001462-42 
Author 
Company 
TFS Trial Form Support 
Address 
Telephone number 
Protocol (amendment #) 
25-NOV-2019
NCT04308395 


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Pelle-926-301E Statistical Analysis Plan 
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TABLE OF CONTENTS 
1. VERSION HISTORY ............................................................................................................ 6 
2. INTRODUCTION .................................................................................................................. 6 
2.1. Study Objectives ........................................................................................................ 6 
2.2. Study Design .............................................................................................................. 6 
3. STUDY PROCEDURES AND ASSESSMENTS ................................................................. 7 
3.1. Safety Assessments .................................................................................................... 7 
3.2. Efficacy Assessments ................................................................................................ 7 
3.3. Exploratory Assessments Patient Reported Outcomes .............................................. 7 
3.4. Baseline Variables ..................................................................................................... 7 
3.4.1. Study drug, study treatment and baseline definitions ................................... 7 
3.4.2. Baseline characteristics ................................................................................. 8 
4. ANALYSIS POPULATIONS ................................................................................................ 8 
4.1. Safety Population ....................................................................................................... 8 
4.2. Other Population ........................................................................................................ 9 
4.2.1. Per-protocol Population ................................................................................ 9 
4.2.2. PK Population ............................................................................................... 9 
5. GENERAL METHODOLOGY AND CONVENTIONS ...................................................... 9 
5.1. Sample size determination ......................................................................................... 9 
5.2. General Methods ........................................................................................................ 9 
5.2.1. Presentation of continuous and qualitative variables .................................... 9 
5.2.2. Definition of study day ............................................................................... 10 
5.2.3. Definition of on-treatment period ............................................................... 10 
5.2.4. Standard derivations and reporting conventions ......................................... 10 
5.2.5. Unscheduled visits ...................................................................................... 11 
5.3. Methods to Manage Missing Data ........................................................................... 11 
5.3.1. Missing data ................................................................................................ 11 
5.3.2. Handling of incomplete dates ..................................................................... 11 
5.3.3. Imputation rules for date of last contact ...................................................... 13 
6. ANALYSES AND SUMMARIES....................................................................................... 13 
6.1. Primary Endpoints ................................................................................................... 13 


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6.1.1. Safety and Tolerability ................................................................................ 13 
6.2. Secondary Endpoint(s) ............................................................................................. 13 
6.2.1. Safety endpoints .......................................................................................... 13 
6.2.2. Efficacy endpoints ....................................................................................... 13 
6.2.3. Exploratory Endpoints ................................................................................ 14 
6.2.4. Pharmacokinetic endpoints ......................................................................... 14 
6.3. Baseline and Other Summaries and Analyses ......................................................... 14 
6.3.1. Baseline summaries ..................................................................................... 14 
6.3.2. Study conduct and patient disposition ......................................................... 16 
6.3.3. Study treatment compliance and exposure .................................................. 16 
6.4. Safety Summaries and Analyses .............................................................................. 17 
6.4.1. Dermal Safety and Tolerability ................................................................... 17 
6.4.2. Adverse Events ........................................................................................... 17 
6.4.3. Laboratory data ........................................................................................... 19 
6.4.4. Vital signs ................................................................................................... 19 
7. REFERENCES ..................................................................................................................... 20 
8. APPENDICES ...................................................................................................................... 21 
APPENDICES 
Appendix 1. aBCCdex Scoring ................................................................................................ 21 
Appendix 2. Skindex-16 Scoring ............................................................................................. 22 
Appendix 3. DLQI Scoring ...................................................................................................... 23 


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ABBREVIATIONS 
 
 
aBCCdex 
Advanced Basal Cell Carcinoma Index 
AE 
Adverse Event 
BCC 
Basal Cell Carcinoma 
BMI 
Body Mass Index 
CI 
Confidence Interval 
CRF 
Case Report Form 
CSP 
Clinical Study Protocol 
CSR 
Clinical Study Report 
DLQI 
Dermatology Quality of Life Index 
DRM 
Data Review Meeting 
EQ-5D-5L 
EuroQol (Quality of Life) using 5 levels 
HHI 
Hedgehog Inhibitor 
ICF 
Informed Consent Form 
IP 
Investigational Product 
MedDRA 
Medical Dictionary for Regulatory Activities 
PP 
Per Protocol 
PRO 
Patient Reported Outcome 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
WOCBP 
Women of Child Bearing Potential 


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1. VERSION HISTORY 
Table 1.  Summary of Major Changes in SAP 
 
Version Date 
Summary of Changes 
Initial 
version 
16-APR-2020 
 
2. INTRODUCTION 
 
This Statistical Analysis Plan (SAP) describes all planned analysis and detailed methodology 
for the Clinical Study Report (CSR) of study Pelle-926-301E. 
This SAP is based on Clinical Study Protocol (CSP) Version 2 dated January 30, 2020. This 
analysis plan overrides any statistical plans outlined in the protocol. 
2.1. Study Objectives 
Primary Objective 
• To assess the safety and tolerability of Patidegib Topical Gel, 2% in patients who have 
completed PellePharm Study Pelle-926-201 or Pelle-926-301 
Secondary Objective 
• To assess the efficacy of Patidegib Topical Gel, 2% in patients who have completed 
PellePharm Study Pelle-926-201 or Pelle-926-301 
2.2. Study Design 
This is a multicenter, open label extension study evaluating the safety of Patidegib Topical 
Gel, 2%, applied topically twice daily to the face of adult subjects with Gorlin syndrome. The 
treatment duration is 12 months, with potential extension beyond this period. 
All study participants will be treated with Patidegib Topical Gel 2%. 
A Screening visit will be mandatory for all subjects, with the possibility for rescreening for 
those who fail screen. Subjects will need to meet all I/E criteria at screening/rescreening visit. 
Completers from study Pelle-926-301 will have their Screening visit after the Study Pelle- 
926-301 End of treatment visit. 
Study visits will occur at quarterly intervals. However for WOCBP, study visits will occur 
monthly. For the first application, the subject will apply the IP to the face at the study site 
under the direction of the Study Coordinator (or designee). The IP should be applied after all 
clinical assessments. Patients will be dispensed a diary to maintain a log of their IP 
application. 


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3. STUDY PROCEDURES AND ASSESSMENTS 
3.1. Safety Assessments 
• Physical Examination Including Vital Sign Results 
• Pregnancy Tests 
3.2. Efficacy Assessments 
• The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 12 
• The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 6 
• The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 12 
• The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 6 
• Change from Baseline to Month 12 in the total number of facial lesions suspicious for 
BCC 
• Count of facial lesions suspicious for BCC over time 
• aBCCdex change in lesion score from Baseline to Month 12 
 
 
3.3. Exploratory Assessments Patient Reported Outcomes 
Exploratory assessments will comprise the following Patient Reported Outcomes (PROs) of 
Quality of Life: 
• Advanced Basal Cell Carcinoma index (aBCCdex) 
• Dermatology Life Quality Index (DLQI) 
• EuroQol Group 5-level EQ-5D (EQ-5D-5L) 
 
 
3.4. Baseline Variables 
3.4.1. Study drug, study treatment and baseline definitions 
In this study, either ‘study drug’, ‘study treatment’ or ‘Investigational product (IP)’ refer 
to Patidegib Topical Gel, 2%. 


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Start and end dates of study treatment: 
The date/time of first dose of study treatment is the earliest date/time of non-zero dosing of 
the study drug. 
The date/time of last dose of study treatment is the latest date/time of non-zero dosing of the 
study drug. 
Definition of baseline: 
In this study, baseline value will refer to the last assessment prior to the first dose. 
3.4.2. Baseline characteristics 
• Inclusion and exclusion criteria 
• Demographic data 
• Medical history 
• Prior and concomitant medication 
 
 
4. ANALYSIS POPULATIONS 
Only patients who signed the Informed Consent Form (ICF) will be included in the analysis 
sets described below. 
4.1. Safety Population 
The safety analysis set will include all patients who had at least one application of study 
treatment. The primary population for analysis of safety and efficacy will be the safety 
population. 
Subgroup analysis will be done for subjects with history of oral or topical HHI in past 6 
months – Yes/No. This will be determined based on the group they were randomized in the 
parent study (i.e. either 201 or 301) and the previous and concomitant medication pages. 
The following efficacy assessments will be analyzed for the forementioned subgroups: 
• The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 12 
• The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 12 
• Change from Baseline to Month 12 in the total number of facial lesions suspicious for 
BCC 


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4.2. Other Population 
4.2.1. Per-protocol Population 
The Per-Protocol set (PPS) will include all subjects in the Safety population who have no 
major Protocol Deviations (PDs). The final criteria for the PPS will be determined when all 
data on PDs are available through a Data Review Meeting (DRM). Data for all patients will 
be assessed to determine if patients meet the criteria for inclusion in each analysis population 
prior to releasing the database (i.e. Database Lock) and classifications will be documented 
per TFS’s (or Sponsor’s) standard operating procedures. Patients who meet any of the 
following criteria may be excluded from the PP analysis set: 
• Patient with any major protocol violations in regards to inclusion/exclusion criteria 
• Patient not completing 12 months of treatment with 80% - 120% treatment compliance 
(see Section 6.3.3) 
• Patient taking any prohibited concomitant medications. 
All PDs will be reported to PellePharm and recorded throughout the study. A tabulation of 
PDs will be included in the final study report. 
4.2.2. PK Population 
Not Applicable. 
5. GENERAL METHODOLOGY AND CONVENTIONS 
5.1. Sample size determination 
As stated in the CSP, this study is not powered for statistical significance. Eligible subjects 
(completers) from PellePharm Studies 926-201 and 926-301 will be enrolled into this study 
up to a maximum of about 200 participants. 
5.2. General Methods 
Endpoints will be summarized based on either the Safety or the PP analysis sets. 
 
5.2.1. Presentation of continuous and qualitative variables 
Continuous variables will be summarized using descriptive statistics i.e., number of non- 
missing values and number of missing values [i.e., n (missing)], mean, median, standard 
deviation (SD), minimum, maximum and first and third quartile (Q1 and Q3). 
Qualitative variables will be summarized by frequency counts and percentages based on 
number of available observations. Missing data will not be summarized as a separate 
category. 
In case the analysis refers only to certain visits, percentages will be based on the number of 
patients still present in the study at that visit, unless otherwise specified. 


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5.2.2. Definition of study day 
Start day of study treatment is the day of the first IP application of study treatment. 
The study day for assessments occurring on or after the start of study treatment will be 
calculated as: 
Study day = Date of the assessment/event - start of study treatment + 1. 
The study day for assessments occurring prior to the first IP application of study treatment 
will be negative and calculated as: 
Study day = Date of the assessment/event - start of study treatment. 
The study day will be displayed in all relevant data listings. 
5.2.3. Definition of on-treatment period 
Safety endpoints will be summarized based on the on-treatment period unless otherwise 
specified. 
On-treatment period is defined as the time from the first IP application of study treatment to 
last IP application of study treatment + 30 days. 
Safety data collected outside the on-treatment period as well as data from unscheduled visits 
will be listed and flagged in listings but not summarized. 
5.2.4. Standard derivations and reporting conventions 
The following conversion factors will be used to convert days into weeks, months or years: 
1 week = 7 days, 1 month = 30.4375 days, 1 year = 365.25 days. 
Demographics and physical measurements: 
• Age [years]: 
- (date of given informed consent - date of birth + 1) / 365.25 
- In case of missing day, day only: Age [years]: (year/month of given informed consent 
– year/month of birth) 
- In case only year of birth is given: Age [years]: (year of given informed consent - 
year of birth) 
The integer part of the calculated age will be used for reporting purposes. 
• BMI (kg/m2) = weight (kg)/[height (m)]2 
For reporting conventions, mean and median should generally be displayed one more 
decimal place than the raw data and standard deviation should be displayed to two more 
decimal places than the raw data. Percentages will be reported to one decimal place. The 


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rounding will be performed to closest integer / first decimal using the common mid-point 
between the two consecutive values. E.g., 3.1 to 3.4 will be rounded to an integer of 3, and 
3.5 to 3.9 will be rounded to an integer of 4. 
5.2.5. Unscheduled visits 
Subjects may return to the site for unscheduled visits in the event of an AE, SAE or as 
deemed necessary by the Investigator. The same procedures as per any other post-Baseline 
Visits may be conducted. Data collected will be reported in the ‘Unscheduled Visit’ eCRF 
page. 
Data from unscheduled visits will be summarized by assigning to closest visit within a 6- 
week window. If two unscheduled visits occur in a row the last one will be assigned (Last 
Observation Carried Forward approach). 
All unscheduled visits info will be listed, flagging those that have been assigned to a pre- 
scheduled visit. 
5.3. Methods to Manage Missing Data 
5.3.1. Missing data 
No missing data imputation is planned. All summaries will use observed data only. Missing 
statistics, e.g. when they cannot be calculated, should be presented as ‘ND’ or ‘NA’. 
5.3.2. Handling of incomplete dates 
5.3.2.1. Adverse events 
Incomplete AE-related dates will be imputed in a conservative manner, as follows: 
• If the AE onset date is missing completely, then the onset date will be replaced by the 
start of study treatment. 
• If only the day part of the AE onset date is missing, but the month and year are equal to 
the start of study treatment, then the AE onset date will be replaced by the start of study 
treatment. For example, if the AE onset date is --/NOV/2014, and study treatment start 
date is 14/NOV/2014, then the imputed AE onset date will be 14/NOV/2014. 
• If both the day and month of the AE onset date are missing but the onset year is equal to 
the start of study treatment, then the onset date will be replaced by the start of study 
treatment. For example, if AE onset date is --/---/2013, and study treatment start date is 
18/JAN/2013, then the imputed AE onset date will be 18/JAN/2013. 
• In all other cases the missing onset day or missing onset month will be replaced by 1. 
• Incomplete stop date will be replaced by the last day of the month (if day is missing only) 
if not resulting in a date later than the date of patient's death. In the latter case the date of 
death will be used to impute the incomplete stop date. 


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• In all other cases the incomplete stop date will not be imputed. If stop date of AE is after 
the date of cut-off then the outcome of AE will be ongoing at cut-off. 
5.3.2.2. Prior and concomitant medications 
Incomplete prior/concomitant medication dates will be imputed as follows: 
• If the medication date is missing completely, then the medication date will be replaced by 
the start of study treatment. 
• If the day of medication date is missing, but the month and year are equal to the start of 
study treatment, then the medication date will be replaced by the start of study treatment. 
For example, if the medication start date is --/NOV/2014, and study treatment start date is 
15/NOV/2014, then the imputed medication start date will be 15/NOV/2014. 
• If both the day and month of medication start date are missing but the start year is equal 
to the start of study treatment, then the medication date will be replaced by the start of 
study treatment. For example, if the medication start date is --/---/2013, and study 
treatment start date is 20/JAN/2013, then the imputed medication start date will be 
20/JAN/2013. 
• In all other cases the missing medication day or missing medication month will be 
replaced by 1. 
• Incomplete stop date will be replaced by the last day of the month (if day is missing only) 
if not resulting in a date later than the date of patient's death. In the latter case the date of 
death will be used to impute the incomplete stop date. 
• In all other cases the incomplete medication stop date will not be imputed. 
5.3.2.3. Exposure 
No imputation will be done for first IP application date. Date of last IP application of study 
drug, if unknown or partially unknown, will be imputed as follows: 
• If the last date of study drug is completely missing and there is no End of Treatment 
eCRF page and no death date, the date of last contact will be the last IP application date 
• If the last date of study drug is completely or partially missing and there is an End of 
Treatment eCRF page available (within the cut-off date), then imputed last IP application 
date is: 
= 31DECYYYY, if only Year is available and Year < Year of EOT date 
= Last day of the month, if both Year and Month are available and Year = Year of EOT 
date and Month < the month of EOT date 
= EOT date, for all other cases 


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5.3.3. Imputation rules for date of last contact 
The date of last contact will be derived for patients at the analysis cut-off using the latest 
complete date among the following: 
• All patient assessment dates (blood draws (laboratory), vital signs, performance status) 
• AE start and end dates 
• Study drug start and end dates 
• Randomization date 
• Withdrawal of consent date 
Only dates associated with actual examinations of the patient will be used in the derivation. 
6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoints 
6.1.1. Safety and Tolerability. 
Safety and tolerability are the primary objectives of this study and will be evaluated by 
reviewing adverse events (see Section 6.4.2), treatment discontinuations and dermal safety 
and tolerability (see Section 6.4.1). 
6.1.1.1. Primary analysis 
No inferential tests will be performed. Data will be summarized through descriptive statistics 
only. 
6.2. Secondary Endpoint(s) 
6.2.1. Safety endpoints 
See Section 6.4. 
6.2.2. Efficacy endpoints 
The efficacy endpoints are: 
 
1. The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 12. 
2. The number of facial BCCs removed by surgery (per Investigator determination) and 
histologically verified as BCC; from Baseline to Month 6. 
3. The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 12. 
4. The number of facial BCCs removed by surgery (per Investigator determination) from 
Baseline to Month 6. 
5. Change from Baseline to Month 12 in the total number of facial lesions suspicious for 
BCC. 


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6. Count of facial lesions suspicious for BCC over time. 
7. aBCCdex change in lesion score from Baseline to Month 12. 
 
All efficacy assessments will be summarized descriptively by visit, depending on the nature 
of the variable. Changes from Baseline will also be displayed. 
6.2.3. Exploratory Endpoints 
The exploratory endpoints will investigate PROs: 
1. Change in aBCCdex Worry About Future Lesions scale score from Baseline to Month 12. 
2. Change in aBCCdex Mental Health scale score from Baseline to Month 12. 
3. Change in aBCCdex Social/Relationships scale score from Baseline to Month 12. 
4. Change in aBCCdex Life Impact scale score from Baseline to Month 12. 
5. Change in Dermatology Life Quality Index (DLQI) total score from Baseline to Month 
12 
6. Shift in EuroQol (Quality of Life) using 5 levels (EQ-5D-5L) from baseline to Month 12 
7. Change in EQ-5D-5L Visual Analog Scale (VAS) from Baseline to Month 12 
 
 
A shift table will be presented for changes from baseline of the EQ-5D-5L dimension scores. 
Additionally, the VAS Scores will be summarized descriptively by visit. 
6.2.4. Pharmacokinetic endpoints 
Not applicable 
6.3. Baseline and Other Summaries and Analyses 
6.3.1. Baseline summaries 
The following analyses will be based on the Safety population. 
6.3.1.1. Demographic characteristics 
Demographic characteristics and physical measurements will be summarized using the 
following information from screening visit in the ‘Demographics’ eCRF page. 
• Demographic characteristics 
- Gender: Male, Female 
- Race: White, Black or African American, Asian, American Indian or Alaska Native, 
Native Hawaiian or other Pacific Islander, Other, Unknown 
- Ethnicity: Hispanic/Latino (Yes/No) 


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- Age (years): summary statistics 
- Geographic Region: 
 United States + Canada 
 United Kingdom + European Union 
• Physical measurements 
- Height (cm) 
- Weight (kg) 
- Body Mass Index (BMI) (kg/m2) 
• Method of contraception 
• Fertility 
Demograhic characteristics and physical measurements will be summarized by descriptive 
statistics. All demographics data will be listed for the safety set. 
6.3.1.2. Medical history 
Medical history will be coded using the most current available version of Medical Dictionary 
for Regulatory Activities (MedDRA) and will be summarized from the ‘Medical History’ 
eCRF page. Medical history will be summarized as the numbers and percentages of patients 
by MedDRA preferred term (PT) as event category and MedDRA primary system organ 
class (SOC) as summary category. Each patient will be counted only once within each PT or 
SOC. 
Medical history will be displayed in terms of frequency tables ordered by primary SOC and 
PT in alphabetical order. 
6.3.1.3. Prior and concomitant medications/therapies 
Prior and concomitant medications/therapies will be captured separately for BCC (facial) and 
other indications. 
 
All medications ongoing in the 12 months prior to Baseline or ongoing at any time during the 
study will be recorded in the eCRF. The start date for all medications that were started during 
the study period must be reported. Likewise, the end date for all medications that were 
discontinued during the study period must be captured. 


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6.3.2. Study conduct and patient disposition 
The following analyses will be performed based on the Safety population. 
6.3.2.1. Patient disposition 
The percentages below will be calculated based on the number of patients in the Safety 
population. 
• Total number of patients enrolled 
• Number and percentage of enrolled patients in each of the analysis populations defined in 
Section 4 
• Number of enrolled patients who discontinued from the study and the main reason for 
discontinuation 
• Number and percentage of enrolled patients who discontinued study treatment overall 
and by the main reason for discontinuation of study treatment 
Additionally, Time to Treatment Discontinuation will be graphically displayed using Kaplan- 
Meier curves. 
6.3.2.2. Protocol deviations 
All protocol violations that impact the safety of the patients and/or the conduct of a study 
and/or its evaluation will be reported. These include: 
• Patients who are treated on the study despite not satisfying the inclusion criteria 
• Patients who develop withdrawal criteria whilst on the study but are not withdrawn 
• Patients who receive an excluded concomitant medication 
• Patient not completing 12 months of treatment within 80% - 120% treatment compliance 
(See section 6.3.3) 
• Deviations from GCP 
The identification of these and other CSR-reportable deviations will be based on the 
inclusion/exclusion criteria or other criteria presented in the protocol. 
6.3.3. Study treatment compliance and exposure 
The following analyses will be based on the Safety population. 
Compliance will be calculated using subject’s diary by dividing doses taken by doses 
planned. 
Compliance will be summarized by visit and will also be a factor in defining the PP 
population as noted in Section 4.3.1. 


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Listings of baseline study drug application, study drug accountability, compliance, and study 
drug interruption will be created. 
6.4. Safety Summaries and Analyses 
The Safety Population will be the primary population for safety evaluations. All summaries 
of AEs and other safety parameters will be based on the safety population. 
6.4.1. Dermal Safety and Tolerability 
Dermal safety and tolerability will be evaluated through assessment of selected local signs 
and symptoms (pain/burning, pruritus, erythema, edema, and crusting) on the face. Any local 
skin reaction that requires use of a concomitant therapy or causes interruption or 
discontinuation of the IP should be reported as a dermal safety event. These events will be 
assessed for severity, relative to the skin reactions scale. 
Shift tables of the frequency of dermal safety and tolerability assessments including 
pain/burning, pruritus, erythema, edema, and crusting will be summarized using counts and 
percentages by visit compared to baseline. 
A listing of all dermal safety and tolerability assessments will be also provided. 
6.4.2. Adverse Events 
AEs will be graded by the investigator and coded using most recent version of the Medical 
Dictionary for Regulatory Activities (MedDRA). 
Treatment-emergent adverse events (TEAEs) are those events with onset dates occurring 
during the on-treatment period for the first time, or if the worsening of an event is during the 
on-treatment period. 
All analyses described Error! Reference source not found. will be based on TEAEs (started 
during the on-treatment period) if not otherwise specified. The AE listings will include all 
AEs (whether treatment-emergent or not). AEs outside the on-treatment period will be 
flagged in the listings. 
• Related Adverse Events: adverse events with relationship to study treatment (as 
recorded on the AE eCRF page, Relationship with study treatment = Possibly / Probably / 
Definitely) reported by the investigator and those of unknown relationship (i.e., no 
answer to the question ‘Relationship with study treatment’). Related AEs are those 
related to any study treatment. 
• Serious Adverse Events (SAE): serious adverse events (as recorded on the AE eCRF 
page, Serious Adverse Event = Yes). 
• Adverse Events Leading to Permanent Treatment Discontinuation: adverse events 
leading to permanent discontinuation of study treatment (as recorded on the AE eCRF 
page, Action taken with study treatment = Drug withdrawn). 


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• Adverse Events Leading to Death: adverse event leading to death (as recorded on the 
AE eCRF page, Outcome = Fatal). 
Unless otherwise specified, AEs will be summarized by number and percentage of patients 
with the AE in the category of interest as described above, by primary SOC and PT in 
decreasing frequency based on the frequencies observed. 
Each patient will be counted only once within each SOC or PT. If a patient experiences more 
than one AE within a SOC or PT for the same summary period, only the AE with the 
strongest relationship or the worst severity, as appropriate, will be included in the summaries 
of relationship and severity. 
6.4.2.1. All adverse events 
Adverse events will be summarized by worst severity per patient, using the latest version of 
MedDRA preferred term (PT) as event category and MedDRA primary system organ class 
(SOC) body term as Body System category. 
In case a patient has events with missing and non-missing severity, the maximum of the non- 
missing severity will be displayed. No imputation of missing severity will be performed. 
AEs will be split between “prior to treatment” and “treatment emergent”. The following 
tables will be created: 
• The overall summary of AEs table will include the frequency (number and percentage) of 
patients with each of the following: 
- TEAEs 
- TEAEs related to IP 
- TEAEs leading to treatment discontinuation 
- TEAEs related to IP leading to treatment discontinuation 
- Paralesional TEAEs 
- Serious TEAEs 
- Serious TEAEs related to IP 
- TEAEs leading to death 
- TEAEs related to IP leading to death 
• TEAEs by SOC and PT and maximum severity 
• TEAEs by closest relationship to study drug 
6.4.2.2. Adverse events leading to discontinuation of study treatment 
The frequency (number and percentage) of patients TEAEs leading to discontinuation of 
Patidegib will be tabulated by SOC and PT. 


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A listing of all AEs leading to treatment discontinuation will also be provided with the 
relevant information. 
6.4.2.3. Deaths 
The frequency (number and percentage) of patients in the safety analysis set who died will be 
tabulated based on information from the ‘End of Treatment’, ‘End of Study’ and ‘Adverse 
Event Log’ eCRF pages. 
6.4.2.4. Serious Adverse Events 
The frequency (number and percentage) of patients with each of the following will be 
presented for treatment-emergent SAEs: 
• SAEs by SOC and PT 
• Related SAEs by SOC and PT 
The listings of all SAEs will also be provided with the relevant information with a flag for 
SAEs with onset outside of the on-treatment period. 
6.4.3. Laboratory data 
Pregnancy test results will be the only laboratory data in this study. Results will be listed for 
the Safety analysis. 
6.4.4. Vital signs 
Vital sign summaries will include all vital sign assessments from the on-treatment period: 
• Body temperature (ºF) 
• Respiration (breaths per minute) 
• Heart Rate (beats per minute) 
• Blood Pressure (systolic and diastolic, in mmHg) 
All vital sign parameters will be summarized using descriptive statistics (mean, SD, median, 
Q1, Q3, minimum, and maximum) of actual values and changes from baseline for each visit 
over time. All vital signs data will be listed as well. 


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7. REFERENCES 
 
 
1. 
Mathias, S.D., Chren, M.M., Crosby, R.D., et al. Reliability and validity of the 
Advanced Basal Cell Carcinoma Index (aBCCdex). British Journal of Dermatology. 
2015;173:713-719. 
2. 
Stokes, M.E., Davis, C.S., and Koch, G.G. (2012), Categorical Data Analysis Using the 
SAS System, Third Edition, Cary, NC: SAS Institute Inc. 
3. 
EuroQol Research Foundation. EQ-5D-5L User Guide, 2019. Available from: 
https://euroqol.org/publications/user-guides. 


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8. APPENDICES 
Appendix 1. aBCCdex Scoring 


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Appendix 2. DLQI Scoring 


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Appendix 3. EQ-5D-5L Scoring 
 


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