Clinical trial NCT05136898
Conditions: Bladder Cancer Urothelial Carcinoma Urothelial Carcinoma Bladder
Keywords: Non-muscle invasive bladder cancer Low grade non-muscle invasive bladder cancer Intermediate risk non-muscle invasive bladder cancer NMIBC UGN-102 Mitomycin
Sponsor: UroGen Pharma Ltd.
Start date: 2021-11-30; Completion date: 2023-02-02
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study aims to demonstrate that home instillation of UGN-102 is a feasible alternative to instillation in a clinical setting, which might mitigate patient challenges (logistical, expense, and comfort) when receiving treatment for low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Detailed description:
The primary objective of this study was to evaluate the feasibility of home instillation of UGN-102 as an alternative to instillation in a clinical setting. Feasibility was assessed by evaluation of safety and tolerability, rate of discontinuation from at home study treatment, and feedback from patients, home health professionals (HHPs), and investigators via standardized questionnaires. The secondary objective of this study was to evaluate the efficacy of UGN-102 for treatment of LG-IR-NMIBC following home instillation. Efficacy was assessed at the 3-month Visit (3 months after the first instillation of UGN-102) by the complete response rate (CRR), defined as the proportion of patients who achieved a complete response (CR) as determined by cystoscopy, for cause biopsy, and urine cytology.

Patients who provided informed consent underwent a Screening Visit to determine eligibility. Screening procedures were to provide evidence of LG-NMIBC and to rule out evidence of high-grade (HG) disease.

Eligible patients were to receive 6 once-weekly intravesical instillations of UGN-102. The first instillation was performed at the investigative site and subsequent instillations were performed at the patient's home by a trained HHP. The HHP was to call the patient 1 to 2 days after each home instillation of UGN-102 to monitor for safety.

At each home instillation visit, the patient and HHP were to complete a feasibility questionnaire. In addition, the patient and investigator were to complete a feasibility questionnaire at the 3-month Visit (end of study) or Early Termination Visit.

Patients were to return to the clinic for the 3-month Visit for determination of response to treatment. Response was determined based on visual evaluation by cystoscopy (white light) (appearance, number, and size of any remaining lesions), interpretation of urine cytology, and for cause biopsy and histopathology of any remaining lesions. Any lesions or suspect tissue were to be biopsied to evaluate for persistence of disease.

Safety was evaluated based on review of adverse events (AEs), laboratory assessments, vital signs, and physical examination.

A patient was considered to have completed the study if the patient completed the 3-month Visit. Following the 3-month Visit, all patients exited the study and continued with standard of care according to their treating physician.

Arms: arm 1: Patients will receive 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin). Treatment Visit 1 will occur at the investigative site and instillation will be performed by a qualified physician. Treatment Visits 2 to 6 will occur at the patient's home and instillation will be performed by a properly trained and qualified home health professional.
Interventions: intervention 1: UGN-102
Intervention descriptions: intervention 1: UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
Protocol BL010 version 1.0 
 
 
1 
Title Page 
Protocol Title: A Phase 3b, Open-Label, Single-Arm, Multicenter Study to Assess the 
Feasibility of Home Instillation of UGN-102 for Treatment of Patients with 
Low-Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at 
Intermediate Risk (IR) of Recurrence 
 
Protocol Number: BL010 
Compound: UGN-102 (mitomycin) for intravesical solution 
Study Phase: 3b 
Sponsor Name: UroGen Pharma Ltd. 
Legal Registered Address: 
9 Ha’Ta’asiya Street 
Ra’anana, Israel 4365405 
 
Regulatory Agency Identifier Number(s): 
IND 138749 
Protocol Status 
Version 
Date 
Original 
1.0 
11 Jun 2021 
 
 
 
 
Property of UroGen Pharma Ltd. 
Confidential 
May not be used, divulged, published or otherwise disclosed without written consent of 
UroGen Pharma Ltd. 


CONFIDENTIAL 
Protocol BL010 version 1.0 
 
 
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Key Roles and Contact Information 
 
Medical Director/Medical Monitor 
, MD, UroGen Pharma 
 
 
 
Study Manager 
, UroGen Pharma 
 
 
Quality Assurance 
, UroGen Pharma 
 
 
qa@urogen.com 
 
Study Logistics 
, UroGen Pharma 
 


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Protocol BL010 version 1.0 
 
 
3 
Table of Contents 
Key Roles and Contact Information ............................................................................................2 
Table of Contents ...........................................................................................................................3 
List of In-text Tables ........................................................................................................................5 
List of In-text Figures ......................................................................................................................5 
List of In-text Appendices ...............................................................................................................6 
Statement of Compliance ..............................................................................................................7 
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis ............................................................................................................................8 
1.2. 
Schema ............................................................................................................................11 
1.3. 
Schedule of Activities .....................................................................................................12 
Abbreviations ...............................................................................................................................14 
2. 
Introduction ...................................................................................................................16 
2.1. 
Study Rationale ...............................................................................................................17 
2.2. 
Benefit-Risk Assessment ................................................................................................18 
2.2.1. 
Risk Assessment .............................................................................................................18 
2.2.2. 
Benefit Assessment .........................................................................................................19 
2.2.3. 
Overall Benefit-Risk Conclusion ....................................................................................19 
3. 
Objectives and Endpoints ............................................................................................20 
4. 
Study Design ..................................................................................................................21 
4.1. 
Overall Design ................................................................................................................21 
4.2. 
Scientific Rationale for Study Design ............................................................................22 
4.3. 
Justification for Dose ......................................................................................................23 
4.4. 
End-of-Study Definition .................................................................................................23 
5. 
Study Population ...........................................................................................................23 
5.1. 
Inclusion Criteria ............................................................................................................23 
5.2. 
Exclusion Criteria ...........................................................................................................24 
5.3. 
Lifestyle Considerations .................................................................................................25 
5.4. 
Screen Failures ................................................................................................................25 
5.5. 
Strategies for Recruitment and Retention .......................................................................25 
5.6. 
Criteria for Temporarily Delaying Administration of Study 
Treatment ........................................................................................................................25 
6. 
Qualified Health Care Personnel.................................................................................26 
6.1. 
Clinical Nurse Educators ................................................................................................26 
6.2. 
Home Health Professionals .............................................................................................26 
7. 
Study Treatment ...........................................................................................................27 
7.1. 
Study Treatment Administered .......................................................................................27 
7.1.1. 
Study Treatment Description ..........................................................................................27 
7.1.2. 
Preparation and Administration Ancillary Supplies .......................................................28 
7.1.3. 
Administration and Dosing .............................................................................................28 


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7.2. 
UGN-102 Single Dose Carton /Handling/Storage/Accountability .................................29 
7.2.1. 
Acquisition and Accountability ......................................................................................29 
7.2.2. 
Formulation, Appearance, Packaging, and Labeling ......................................................30 
7.2.3. 
Product Storage and Stability..........................................................................................30 
7.2.4. 
Admixture .......................................................................................................................30 
7.2.5. 
Product Quality Complaint Handling .............................................................................31 
7.3. 
Study Intervention Compliance ......................................................................................31 
7.4. 
Dose Modification ..........................................................................................................31 
7.5. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................31 
7.6. 
Treatment of Overdose ...................................................................................................31 
7.7. 
Past/Concomitant and Prohibited Therapy .....................................................................32 
7.7.1. 
Rescue Medicine .............................................................................................................32 
8. 
Discontinuation of Study Treatment and Patient 
Discontinuation/Withdrawal........................................................................................33 
8.1. 
Discontinuation of Study Treatment ...............................................................................33 
8.1.1. 
Temporary Withholding of Study Treatment .................................................................33 
8.1.2. 
Rechallenge .....................................................................................................................33 
8.1.3. 
Withdrawal of Consent for Home Instillation of Study Treatment ................................33 
8.2. 
Patient Discontinuation/Withdrawal from the Study ......................................................33 
8.3. 
Lost to Follow-up............................................................................................................34 
9. 
Study Assessments and Procedures.............................................................................35 
9.1. 
Study Assessments and Procedures by Visit ..................................................................35 
9.2. 
Efficacy Assessments .....................................................................................................35 
9.2.1. 
Measurements for Evaluation of Response at 3-month Visit .........................................35 
9.2.2. 
Evaluation of Treatment Response at 3-month Visit (Disease 
Assessment) ....................................................................................................................35 
9.2.3. 
Pathological Evaluation ..................................................................................................36 
9.3. 
Safety Assessments .........................................................................................................36 
9.3.1. 
Physical Examinations ....................................................................................................37 
9.3.2. 
Vital Signs .......................................................................................................................37 
9.3.3. 
Clinical Safety Laboratory Assessments ........................................................................37 
9.3.4. 
Urinalysis ........................................................................................................................39 
9.3.5. 
Pregnancy Testing ...........................................................................................................39 
9.4. 
AEs, SAEs, and Other Safety Reporting ........................................................................39 
9.4.1. 
AEs and SAEs .................................................................................................................40 
9.4.2. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................43 
9.4.3. 
Method of Detecting AEs and SAEs ..............................................................................44 
9.4.4. 
Follow-up of AEs and SAEs ...........................................................................................44 
9.4.5. 
Regulatory Reporting Requirements for SAEs ...............................................................44 
9.4.6. 
Serious Adverse Event Reporting ...................................................................................45 
9.4.7. 
Pregnancy ........................................................................................................................46 
9.4.8. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................................46 
9.4.9. 
AESIs ..............................................................................................................................46 


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Protocol BL010 version 1.0 
 
 
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9.5. 
Pharmacokinetics ............................................................................................................46 
9.6. 
Genetics and/or Pharmacogenomics ...............................................................................46 
9.7. 
Biomarkers ......................................................................................................................47 
9.8. 
Immunogenicity Assessments.........................................................................................47 
9.9. 
Home Instillation Feasibility Questionnaires .................................................................47 
10. 
Statistical Considerations .............................................................................................48 
10.1. 
Statistical Hypotheses .....................................................................................................48 
10.2. 
Sample Size Determination ............................................................................................48 
10.3. 
Analysis Set ....................................................................................................................48 
10.4. 
Statistical Analyses .........................................................................................................48 
10.4.1. General Considerations ...................................................................................................48 
10.4.2. Primary Endpoint(s) ........................................................................................................48 
10.4.3. Secondary Efficacy Endpoint(s) .....................................................................................50 
10.4.4. Other Analysis ................................................................................................................50 
10.5. 
Interim Analysis ..............................................................................................................50 
11. 
Supporting Documentation and Operational Considerations ..................................51 
11.1. 
Regulatory, Ethical, and Study Oversight Considerations .............................................51 
11.1.1. Regulatory and Ethical Considerations ...........................................................................51 
11.1.2. Finance and Insurance .....................................................................................................51 
11.1.3. Data Protection, Confidentiality, and Privacy ................................................................52 
11.1.4. Data Review Committee .................................................................................................53 
11.1.5. Dissemination of Clinical Study Data .............................................................................53 
11.1.6. Safety Oversight..............................................................................................................53 
11.1.7. Clinical Monitoring .........................................................................................................53 
11.1.8. Data Quality Assurance ..................................................................................................54 
11.1.9. Data Handling and Record Keeping ...............................................................................55 
11.1.10. Protocol Deviations .........................................................................................................55 
11.1.11. Source Documents ..........................................................................................................56 
11.1.12. Study and Site Start and Closure ....................................................................................56 
11.1.13. Publication Policy ...........................................................................................................57 
11.1.14. Conflict of Interest Policy ...............................................................................................57 
12. 
References ......................................................................................................................58 
 
List of In-text Tables 
Table 1 UGN-102 Components .................................................................................................. 27 
Table 2 Vial Composition of Mitomycin for Solution................................................................ 28 
Table 3 Physical Examinations ................................................................................................... 37 
Table 4 Laboratory Safety Assessments ..................................................................................... 38 
 
List of In-text Figures 
Figure 1 Structure of Mitomycin, USP ........................................................................................ 27 
 


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List of In-text Appendices 
Appendix A. Patient Questionnaire ............................................................................................ 61 
Appendix B. Home Health Professional Questionnaire ............................................................. 63 
Appendix C. Investigator Questionnaire .................................................................................... 64 
 


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Statement of Compliance 
The study will be conducted in accordance with International Council for Harmonisation 
Good Clinical Practice (ICH GCP) and the applicable United States (US) Code of Federal 
Regulations (CFR). The Principal Investigator will assure that no deviation from, or changes to 
the protocol will take place without prior agreement from the Sponsor, except where necessary to 
eliminate an immediate hazard(s) to the study patients. 
The protocol, informed consent form(s), recruitment materials, and all patient materials will be 
submitted to the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) for 
review and approval. Approval of both the protocol and the consent form must be obtained before 
any patient is enrolled. Any amendment to the protocol will require review and approval by the 
IRB/IEC before the changes are implemented to the study. All changes to the consent form will 
be IRB/IEC approved; a determination will be made regarding whether a new consent needs to be 
obtained from patients who provided consent, using a previously approved consent form. 


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Protocol BL010 version 1.0 
 
 
8 
1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Phase 3b, Open-Label, Single-Arm, Multicenter Study to Assess the 
Feasibility of Home Instillation of UGN-102 for Treatment of Patients with 
Low-Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at 
Intermediate Risk (IR) of Recurrence 
Overall Design: This Phase 3b, open-label, single-arm, multicenter study is designed to assess 
the feasibility of home instillation of UGN-102 (mitomycin) for intravesical solution in 
approximately 10 patients with low-grade (LG) intermediate risk (IR) non-muscle-invasive 
bladder cancer (NMIBC). 
The primary objective of this study is to evaluate the feasibility of home instillation of UGN-102 
as an alternative to instillation in a clinical setting. Feasibility will be assessed by evaluation of 
safety and tolerability, rate of discontinuation from at home study treatment, and feedback from 
patients, home health professionals, and investigators via standardized questionnaires. The 
secondary objective of this study is to evaluate the efficacy of UGN-102 for the treatment of 
LG IR NMIBC following home instillation. Efficacy will be assessed at the 3-month Visit 
(3 months after the first instillation of UGN-102) by complete response rate (CRR), defined as 
the proportion of patients who achieved complete response (CR) as determined by cystoscopy, 
for cause biopsy, and urine cytology. 
Patients who provide informed consent will undergo a Screening Visit to determine eligibility. 
Approximately 10 patients ≥ 18 years of age with LG IR NMIBC who meet the eligibility 
criteria will receive 6 once weekly intravesical instillations of UGN-102. The first instillation 
will be performed at the investigative site and subsequent instillations will be performed at the 
patient’s home by a properly trained and qualified home health professional. 
End-of-study (EOS) is defined as the last patient last visit (LPLV). The EOS will be declared 
after all patients have completed the 3-month Visit (7 weeks ± 1 week after the final instillation 
of UGN-102).  
Following the 3-month Visit, all patients will exit the study and continue with standard of care 
according to their treating physician. 
Objectives and Endpoints: 
Objective 
Endpoints 
Primary 
 
To evaluate the feasibility of home 
instillation of UGN-102 for treatment of 
patients with LG IR NMIBC 
Feasibility will be assessed by evaluation of: 
• 
Safety and tolerability 
o Reporting of AEs, including SAEs and AESIs 
o Standard clinical laboratory tests (hematology, 
serum chemistry, and urinalysis) 
o Physical examination and vital sign measurements 
• 
Rate of discontinuation from at home study treatment 


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Protocol BL010 version 1.0 
 
 
9 
Objective 
Endpoints 
• 
Feedback from patients, home health professionals, and 
investigators via standardized questionnaires 
Secondary 
 
To evaluate the efficacy of UGN-102 
for treatment of LG IR NMIBC 
following home instillation with respect 
to complete response rate (CRR) at the 
3-month disease assessment 
CRR is defined as the proportion of patients who achieved CR 
at the 3-month Visit (3 months after the first instillation of 
study treatment) as determined by cystoscopy, for cause biopsy, 
and urine cytology 
AE = adverse event; AESI = adverse event of special interest; CR = complete response; CRR = complete response 
rate; LG IR NMIBC = low-grade intermediate risk non-muscle-invasive bladder cancer; SAE = serious adverse event. 
Inclusion Criteria:  
1. Capable of giving written informed consent, which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this 
protocol. 
2. Patient must be ≥ 18 years of age at the time of signing the ICF. 
3. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed 
by cold cup biopsy at Screening or within 8 weeks before Screening. 
4. Has IR disease, defined as having 1 or 2 of the following: 
• presence of multiple tumors. 
• solitary tumor > 3 cm. 
• recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at 
the initial Screening Visit). 
5. Negative voiding cytology for high-grade (HG) disease within 6 weeks before Screening. 
6. Has adequate organ and bone marrow function as determined by routine laboratory tests 
as below: 
• Leukocytes ≥ 3,000/μL (≥ 3×109/L). 
• Absolute neutrophil count ≥ 1,500/μL (≥ 1.5×109/L). 
• Platelets ≥ 100,000/μL (≥ 100×109/L). 
• Hemoglobin ≥ 9.0 g/dL. 
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN). 
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 × ULN. 
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN. 
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. 
7. Has no evidence of active urinary tract infection (UTI) at the Screening and baseline visits. 
8. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) 
by an appropriately trained home health professional. 


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Protocol BL010 version 1.0 
 
 
10 
9. Contraceptive use by men and women should be consistent with local regulations regarding 
the methods of contraception for clinical study participants. Women of childbearing 
potential (defined as premenopausal women who have not been sterilized), including 
female patients and female partners of male patients, must be willing to use 2 acceptable 
forms of effective contraception from first instillation through 6 months post treatment. 
Acceptable methods of birth control that are considered to have a low failure rate (ie, less 
than 1% per year) when used consistently and correctly include implants, injections, 
combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only 
hormonal), condoms with spermicide, sexual abstinence, or vasectomized partner. 
10. Has an anticipated life expectancy of at least the duration of the trial. 
Exclusion Criteria: 
1. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) 
within previous 1 year. 
2. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years. 
3. Known allergy or sensitivity to mitomycin that in the Investigator’s opinion cannot be 
readily managed. 
4. Clinically significant urethral stricture that would preclude passage of a urethral catheter. 
5. History of: 
• neurogenic bladder. 
• active urinary retention. 
• any other condition that would prohibit normal voiding. 
6. Past or current T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent 
upper tract urothelial carcinoma (UTUC). 
7. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the 
Investigator, the patient would be unable to comply with the protocol. 
8. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years 
except for a single dose of chemotherapy immediately after any previous transurethral 
resection of bladder tumors (TURBT). 
9. Has participated in a study with an investigational agent or device within 30 days of 
enrollment. 
Number of Patients: Approximately 10 patients will be enrolled and treated in this study.  
Number of Investigative Sites: The study will be conducted at approximately 5 investigative 
sites in the US. 
Qualified Health Care Personnel: The study will be conducted by appropriately trained 
urologists and qualified home health professionals. Clinical nurse educators (CNEs) will train 
pharmacy personnel on study treatment preparation and study personnel (eg, investigators and 
home health professionals) on the UGN-102 instillation procedure. 
Treatment and Duration: Eligible patients will be treated with 6 once-weekly intravesical 
instillations of UGN-102 (75 mg mitomycin in 56 mL admixture; 1.33 mg mitomycin per 1 mL 
of admixture). 
Data Review Committee: None. 


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Protocol BL010 version 1.0
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Statistical Analyses: No formal hypothesis will be tested. The sample size of this study 
(approximately 10 patients) is based on feasibility. 
Safety data will be analyzed descriptively. Point estimates of the secondary endpoint CRR at the 
3-month Visit along with the exact 95% confidence interval (CI) will be summarized. 
The Safety Analysis Set that includes all patients who received any dose of UGN-102 will serve 
as the primary population for the analyses of safety and efficacy data in this study.
No interim analysis will be conducted. The final analysis will be performed after all patients 
complete the end of study visit or are withdrawn from the study. 
1.2.
Schema
a. 
One day after every home instillation (+1 day).


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Protocol BL010 version 1.0 
 
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1.3. 
Schedule of Activities 
Procedures 
Screening 
Period a 
Treatment 
Visit 1 
(Baseline) 
Treatment 
Visit 2  
Treatment 
Visit 3  
Treatment 
Visit 4  
Treatment 
Visit 5  
Treatment 
Visit 6  
3-month Visit 
(EOS) 
ET 
Planned Location 
Clinic 
Clinic 
Home 
Home 
Home 
Home 
Home 
Clinic 
Clinic 
Day/Week/Month 
D-14 to D-1 
or  
D-28 to D-1 
D1/W1 
D8/W2 
D15/W3 
D22/W4 
D29/W5 
D36/W6 
3 months 
(7 weeks ±1 week 
after final 
instillation) 
NA 
Window b 
NA 
D-1 
+1/+7 d 
-1/+3 d 
-1/+3 d 
-1/+3 d 
-1/+3 d 
-1/+3 d 
±1 week 
NA 
Informed consent 
X c 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical/surgical & smoking history 
X 
 
 
 
 
 
 
 
 
Concomitant medication review  
X d 
X 
X 
X 
X 
X 
X 
X 
X 
Full physical examination e 
X 
 
 
 
 
 
 
 
 
Urological examination f 
X 
X 
 
 
 
 
 
X 
X 
Clinical assessment before study drug instillation g 
 
 
X 
X 
X 
X 
X 
 
 
Height and weight  
X 
 
 
 
 
 
 
 
 
Vital signs h  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology/serum chemistry i  
X 
X 
 
 
 
 
 
X 
X 
Urinalysis j  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test (WOCBP only) k  
X 
 
 
 
 
 
 
X 
X 
Adverse event review and evaluation l  
X 
X 
X 
X 
X 
X 
X 
X 
X 
CT Urogram, retrograde pyelogram, or MRI m 
X 
 
 
 
 
 
 
 
 
Cold cup biopsy n 
X 
 
 
 
 
 
 
 
 
Cystoscopy (white light) 
X 
 
 
 
 
 
 
X 
 
Urine cytology 
X o 
 
 
 
 
 
 
X 
 
Administer study treatment p  
 
X 
X 
X 
X 
X 
X 
 
 
Patient questionnaire q 
 
 
X 
X 
X 
X 
X 
X 
X 
Home health professional questionnaire r 
 
 
X 
X 
X 
X 
X 
 
 
Investigator questionnaire s 
 
 
 
 
 
 
 
X 
X 
Telephone call for safety oversight after home instillation t  
 
 
X 
X 
X 
X 
X 
 
 
Biopsy remaining lesions if indicated by cystoscopy 
 
 
 
 
 
 
 
X u 
 
Disease Assessment 
 
 
 
 
 
 
 
X u 
 
Study Exit 
 
 
 
 
 
 
 
X v 
 
Complete eCRFs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE = adverse event; AESI = adverse event of special interest; CT = computed tomography; d = day; D = visit day; eCRF = electronic case report form; EOS = end-of-study; ET = early 
termination; HG = high-grade; ICF = informed consent form; LG = low-grade; MRI = magnetic resonance imaging; NA = not applicable; NMIBC = non-muscle-invasive bladder cancer; 
SAE = serious adverse event; UC = urothelial carcinoma; UTUC = upper tract urothelial carcinoma; W = visit week; WOCBP = women of child-bearing potential. 


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Protocol BL010 version 1.0 
 
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a. 
The Screening Period is up to 14 days for patients who do not need a Screening biopsy and up to 28 days for patients who need a Screening biopsy. Screening procedures are required to 
provide evidence of LG NMIBC and no evidence of HG disease. 
b. 
Windows are provided to accommodate patient logistics in scheduling. Treatment instillations should occur 6 to10 days apart. Every effort should be made to minimize the time interval 
between diagnosis and Treatment Visit 1 (the maximum interval from end of Screening to first instillation should be ≤ 7 days). 
c. 
Obtain written informed consent before any study-related procedures are performed.  
d. 
Any past therapy (eg, pharmacological or surgical interventions) related to UC will be recorded during Screening. 
e. 
A full physical examination will be performed at the Screening Visit by a physician at the investigative site (Section 9.3.1). Additional full physical examinations may be performed 
during the study if clinically indicated. 
f. 
A urological examination will be performed at the Screening Visit, Treatment Visit 1, and at the 3-month Visit (or ET) by a physician at the investigative site (Section 9.3.1). The 
urological examination should be performed before cystoscopy at relevant visits. Additional urological examinations may be performed during the study if clinically indicated. Any 
clinically relevant changes in urological examinations will be recorded on the AE sections of the eCRF. 
g. 
Clinical assessment will be performed before study drug instillation. Body systems to be reviewed include general appearance and urethral meatus (Section 9.3.1). Abnormal findings 
observed at home instillation visits will be documented and reported by the home health professional to the investigative site during the visit. 
h. 
Vital signs include body temperature, pulse rate, respiratory rate, and blood pressure (Section 9.3.2).  
i. 
Hematology and serum chemistry samples will be tested at the local laboratory. Parameters to be analyzed in this study are listed in Section 9.3.3. Other parameters that are part of the 
local laboratory standard panel may be reported in addition to the protocol-specified parameters. 
j. 
Dipstick on-site and at home; culture and sensitivity added at Screening, and when otherwise clinically indicated, if suggestive for infection (at local laboratory) (Section 9.3.4). 
k. 
Urine or serum pregnancy test (at local laboratory). See Section 9.3.5 for the definition of a female of childbearing potential. 
l. 
Adverse events will be collected from the signing of the ICF until the 3-month Visit (EOS). The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 9.4.1, Section 9.4.5, and Section 9.4.6. Investigators are to report AEs (including AESIs) in a consistent 
manner as described in Section 9.4.2. 
m. 
CT Urogram, retrograde pyelogram, or MRI (if other tests are contraindicated) to rule out UTUC (acceptable if performed within 6 months before Screening Visit) (results assessed locally). 
n. 
A single representative cold cup biopsy to confirm LG tumor will be performed only if not already performed within 8 weeks before Screening Visit. This is a diagnostic biopsy to 
demonstrate histopathology of tumor and resection of the tumor is not to performed. 
o. 
No cytology needed if results from a prior cytology within 6 weeks before Screening are available.  
p. 
Treatment Visit 1 will occur at the investigative site and study treatment instillation will be performed by a qualified physician. Treatment Visits 2 to 6 will occur at the patient’s home 
and study treatment instillation will be performed by a properly trained and qualified home health professional. The patient will be monitored for AEs during and for at least 60 minutes 
after each study treatment instillation. If the patient withdraws consent for in-home instillation of study treatment, the patient may continue treatment and scheduled assessments at the 
investigative site (Section 8.1.3). Administration of study treatment will be documented in the patient file, eCRF, and in the Drug Administration Records (Section 7.1.3.1). 
q. 
Patient questionnaire: Part 1 must be completed after home instillation of study treatment at Treatment Visits 2 to 6; Part 2 must be completed at the 3-month Visit (EOS) or ET Visit) 
(Appendix A). 
r. 
Home health professional questionnaire: Part 1 must be completed after home instillation of study treatment at Treatment Visits 2 to 6; Part 2 must be completed after home instillation 
of study treatment at Treatment Visits 3 to 6 (Appendix B). 
s. 
Investigator questionnaire: Must be completed at the 3-month Visit (EOS) or ET Visit (Appendix C). 
t. 
The home health professional will call the patient 1 day (+1 day) after each home instillation of study treatment to monitor for safety (Section 7.1.3.1). 
u. 
Efficacy assessment (approximately 3 months after the first instillation of study treatment). Biopsies may be needed at the 3-month Visit (EOS) if any remaining lesions are visualized 
during cystoscopy (Section 9.2). 
v. 
Following the 3-month Visit, all patients will exit the study and continue with standard of care according to their treating physician. 
 


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Abbreviations 
ADL 
activities of daily living 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BCG 
Bacillus Calmette-Guérin 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CNE 
clinical nurse educator 
CR 
complete response 
CRR 
complete response rate 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
durable complete response 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EOS 
end-of-study 
ET 
early termination 
FDA 
Food and Drug Administration  
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HG 
high-grade 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IP 
investigational products 
IR 
intermediate risk 
IRB 
Institutional Review Board 
LG 
low-grade 
LPLV 
last patient last visit 
LUTS 
lower urinary tract symptoms 
MedDRA 
Medical Dictionary for Regulatory Activities 


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NCR 
non-complete response 
NDD 
no detectable disease 
NMIBC 
non-muscle-invasive bladder cancer 
PI 
Principal Investigator 
PQC 
product quality complaint 
PT 
preferred term 
QC 
quality control 
QTL 
quality tolerance limit 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SEER 
Surveillance, Epidemiology, and End Results (Program) 
SMP 
Study Monitoring Plan 
SoA 
Schedule of Activities 
SRT 
safety review team 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TURBT 
transurethral resection of bladder tumors 
UADR 
unexpected adverse drug reaction 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
US 
United States 
USP 
United States Pharmacopeia 
UTI 
urinary tract infection 
UTUC 
upper tract urothelial carcinoma 
 


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2. 
Introduction 
Non-Muscle-Invasive Bladder Cancer 
Bladder cancer is the sixth most common cancer in the US, with an expected 81,000 new cases 
diagnosed in 2020 (ACS, 2020). At the time of diagnosis, 75% of patients present with NMIBC 
(Babjuk et al, 2019; Monteiro et al, 2019). NMIBC includes a clinically heterogeneous group of 
cancers with a wide range of recurrence and progression probabilities (Chang et al, 2016). 
Therefore, treatment guidelines recommend classifying patients with NMIBC as being at low, 
intermediate, or high risk of disease recurrence and/or progression (Babjuk et al, 2019; Chang 
et al, 2016; Kamat et al, 2014). While the management of low risk and high-risk patients appears 
clear, the best treatment option for intermediate risk patients remains undefined (Monteiro et al, 
2019). Based on analysis of the Surveillance, Epidemiology, and End Results (SEER) Program 
SEER*Stat Database, UroGen estimates that LG IR NMIBC represents approximately 25% of 
newly diagnosed bladder cancer cases in the US (SEER Program, 2019). 
The current standard of care for treatment of LG IR NMIBC is TURBT under general anesthesia 
(NCCN, 2020; Chang et al, 2016). Due to the persistent and recurrent nature of the disease (30% 
to 50% recur at 1 year; Babjuk et al, 2019), patients with LG IR NMIBC often endure repeated 
TURBTs under general anesthesia, which research has shown to be associated with significant 
postoperative and long-term morbidity and an increased risk of overall death (Erikson et al, 2020; 
Pereira et al, 2019; Avallone et al, 2017; Ghali et al, 2016; Matulewicz et al, 2015; Patel et al, 
2015; De Nunzio et al, 2014; Hollenbeck et al, 2006; Balbay et al, 2005). Rates of 30-day 
complications (11%), unplanned hospital readmissions (5%), and mortality (1%) following 
TURBT yield a significant number of patients at risk given the high volume of this procedure 
(Erikson et al, 2020; Patel et al, 2015; Rambachan et al, 2014). The totality of evidence, 
including procedural limitations (eg, incomplete resection of tumors; Daneshmand et al, 2018; 
Miyake et al, 2016), postoperative complications, and the high recurrence rate of NMIBC, 
suggests that the current, primarily surgical approach to treatment is suboptimal. 
Short-term, chemoablative therapy with UGN-102 has the potential to serve as a primary 
nonsurgical treatment option for LG IR NMIBC, especially among this population of 
predominantly elderly and multimorbid patients, by whom surgery and anesthesia are poorly 
tolerated. Studies in the peer-reviewed literature (Lindgren et al, 2020; Mostafid et al, 2020; 
Colombo et al, 2012) and data from the UGN-102 clinical development program suggest that 
chemoablation with mitomycin may obviate the need for surgery in some patients or reduce the 
perioperative morbidity associated with surgery secondary to lower volume disease, and may be 
associated with fewer clinically significant adverse effects. 
UGN-102 
UGN-102 (mitomycin) for intravesical solution is a reverse thermal gel formulation of 
mitomycin designed for initial nonsurgical treatment of LG IR NMIBC, and to potentially 
obviate the need for repetitive TURBT. The reverse thermal properties of UGN-102 allow for the 
local administration of mitomycin as a liquid in a cooled state, with subsequent conversion to a 
semi-solid gel depot at body temperature following instillation into the bladder cavity. The gel 
slowly disintegrates and is excreted by normal urine flow, allowing for the sustained release of 


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mitomycin over a period of 4 to 6 hours. The prolonged exposure of tumor cells to mitomycin 
leads to improved chemoablation compared with aqueous preparations of mitomycin. 
The efficacy and safety of UGN-102 for the treatment of patients with LG IR NMIBC was 
evaluated in a Phase 2b, single-arm, multicenter study (BL005). Intravesical instillation of 
UGN-102 once weekly for 6 weeks resulted in high rates of CR at 3 months and durable 
complete response (DCR) at 12 months after the start of study treatment. A total of 63 patients 
were enrolled and treated with UGN-102. Forty-one (65.1%) patients achieved the primary 
endpoint of CR at 3 months after the first instillation of UGN-102 (95% CI of CR rate: 52.0, 
76.7), and 25/41 (61.0%) patients had a DCR at 12 months after the first instillation (95% CI of 
DCR rate: 44.5, 75.8). The 9-month duration of response rate as estimated by the Kaplan-Meier 
method was 72.5% (95% CI: 54.4, 84.3), ie, the probability that a patient will maintain CR for at 
least 9 months is 72.5%. The overall safety profile of UGN-102 was favorable, with primarily 
mild to moderate adverse events (AEs), no treatment-related serious adverse events (SAEs) or 
hospitalizations, low number of treatment discontinuations, and no clinically meaningful trends 
or pattern of changes identified in laboratory parameters, vital signs, or physical examinations.  
Based on the favorable tolerability profile and the vulnerability of this patient population, the 
intent of this study is to demonstrate that UGN-102 may be safely and feasibly administered in the 
home setting.  
Further details regarding the development of UGN-102 can be found in the UGN-102 
Investigator’s Brochure (IB). 
2.1. 
Study Rationale 
This study aims to demonstrate that home instillation of UGN-102 is a feasible alternative to 
instillation in a clinical setting. Potential advantages of home instillation include but are not 
limited to: 
• moving healthcare out of the clinical setting and into a patient’s home, potentially 
reducing hospital resource utilization. 
• decreased risk of exposure to infections observed in the healthcare setting. 
• simplifying travel logistics, decrease travel expenditures, decrease clinic waiting periods 
for the patient.  
• decreased burden to family members who might otherwise need to transport patient to 
and from clinical setting. 
• receiving cancer treatment in a familiar environment.  


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2.2. 
Benefit-Risk Assessment 
Further details regarding the benefit-risk profile of UGN-102 for treatment of LG IR NMIBC can 
be found in the UGN-102 IB. 
2.2.1. 
Risk Assessment 
Cystitis and Lower Urinary Tract Symptoms  
Cystitis and other lower urinary tract symptoms (LUTS) may develop. These symptoms are well 
known in relation to standard mitomycin instillations and are not specific to UGN-102. Urine 
tests, including urinalysis and urine culture as indicated, will be checked regularly during the 
study to monitor for potential UTI. Any signs and/or symptoms of UTI will be treated by the 
Investigator according to local practice. 
Toxicity Associated with Systemic Absorption/Local Irritation 
Bladder toxicity and rarely bone marrow toxicity (thrombocytopenia and leukopenia) are 
considered possible risks for patients when mitomycin is administered topically. Complete blood 
count and renal and liver function tests will be checked during the study (Table 4), and the 
Investigator will follow any clinically significant abnormality until it is resolved, stabilized, or 
otherwise managed (Section 9.3.3). 
Allergic Response to Mitomycin 
Allergic reactions during mitomycin bladder instillations are well described and have been 
observed during previous studies with UGN-102. Toxicities were generally manageable by 
treating patients with antihistamine drugs before and after treatment, and with systemic steroids 
as needed. Signs of an allergic response will be closely monitored during the study and managed 
by the Investigator according to local practice. 
Instillation Procedure  
The insertion of a urethral catheter requires manipulation of the urethra and bladder. Some pain 
and discomfort are expected given the intravesical route of administration.  
Potential risks of urethral catheterization include catheter associated UTIs, soreness, bleeding, 
bruising, and kidney infections. 
The first study treatment instillation will be performed at the investigative site by a qualified 
physician. Treatment Visits 2 to 6 will occur at the patient’s home and study treatment 
instillation will be performed by a properly trained and qualified home health professional. To 
the extent possible, the same home health professional will perform home instillation of study 
treatments for a given patient.  
If the assigned home health professional is unable to perform the study treatment instillation on a 
scheduled dose day, another trained and qualified home health professional will perform the 
required study treatment instillation (Section 7.1.3.1). 
The patient will be monitored for AEs during and for at least 60 minutes after each study 
treatment instillation.  


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2.2.2. 
Benefit Assessment 
The potential advantages of instillation of mitomycin in hydrogel include: 
• Extended exposure of drug for up to 6 hours (compared with 1.5 to 2 hours in standard 
instillation). Published literature indicates that duration of tumor exposure to 
chemotherapy is critical to its ablative response. Thus, the effectiveness of tumor ablation 
is increased by longer dwell times. 
• The hydrogel protects mitomycin from being diluted by urine, which leads to longer 
stable chemotherapy concentration levels. 
These characteristics of UGN-102 (mitomycin + sterile hydrogel) are expected to improve 
mitomycin treatment efficacy and provide an alternative mode of ablation for NMIBC, which 
may be simpler and potentially better tolerated than current treatment modalities. 
Instillation Procedure 
Potential benefits of providing medical care at home include patient convenience, comfort and 
logistical ease, decreased risk of nosocomial infections, decreased exposure to others who may 
transmit infections such as the COVID-19 virus, influenza, or common “cold” virus 
(eg, rhinoviruses and adenoviruses), and decreased burden on family members who might 
otherwise be responsible for transporting patients to and from procedures. Other potential 
benefits include increased patient engagement and compliance in study procedures.  
2.2.3. 
Overall Benefit-Risk Conclusion 
Overall, based on the efficacy and safety results observed to date, UGN-102 has a favorable 
benefit-risk profile for the treatment of LG IR NMIBC. Additionally, based on the favorable 
tolerability profile and the vulnerability of this patient population, home instillation of UGN-102 
may be a feasible treatment paradigm and offer potential advantages compared with instillation 
in a clinical setting. 


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3. 
Objectives and Endpoints 
Objective 
Endpoints 
Primary 
 
To evaluate the feasibility of home 
instillation of UGN-102 for treatment of 
patients with LG IR NMIBC 
Feasibility will be assessed by evaluation of: 
• 
Safety and tolerability 
o Reporting of AEs, including SAEs and AESIs 
o Standard clinical laboratory tests (hematology, 
serum chemistry, and urinalysis) 
o Physical examination and vital sign measurements 
• 
Rate of discontinuation from at home study treatment 
• 
Feedback from patients, home health professionals, and 
investigators via standardized questionnaires 
Secondary 
 
To evaluate the efficacy of UGN-102 
for treatment of LG IR NMIBC 
following home instillation with respect 
to complete response rate (CRR) at the 
3-month disease assessment 
CRR is defined as the proportion of patients who achieved CR 
at the 3-month Visit (3 months after the first instillation of 
study treatment) as determined by cystoscopy, for cause biopsy, 
and urine cytology 
AE = adverse event; AESI = adverse event of special interest; CR = complete response; CRR = complete response 
rate; LG IR NMIBC = low-grade intermediate risk non-muscle-invasive bladder cancer; SAE = serious adverse event. 
 


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4. 
Study Design 
4.1. 
Overall Design 
This Phase 3b, open-label, single-arm, multicenter study is designed to assess the feasibility of 
home instillation of UGN-102 (mitomycin) for intravesical solution in approximately 10 patients 
with LG IR NMIBC. 
The primary objective of this study is to evaluate the feasibility of home instillation of UGN-102 as 
an alternative to instillation in a clinical setting. Feasibility will be assessed by evaluation of safety 
and tolerability, rate of discontinuation from at home study treatment, and feedback from patients, 
home health professionals, and investigators via standardized questionnaires. The secondary 
objective of this study is to evaluate the efficacy of UGN-102 for the treatment of LG IR NMIBC 
following home instillation. Efficacy will be assessed at the 3-month Visit (3 months after the first 
instillation of UGN-102) by CRR, defined as the proportion of patients who achieved CR as 
determined by cystoscopy, for cause biopsy, and urine cytology. 
Patients who provide informed consent will undergo a Screening Visit to determine eligibility. 
The Screening Period is up to 14 days for patients who do not need a Screening biopsy and up to 
28 days for patients who need a Screening biopsy. Screening procedures are required to provide 
evidence of LG NMIBC and to rule out evidence of HG disease (Section 1.3).  
A single representative cold cup biopsy to confirm LG tumor will be performed only if not 
already performed within 8 weeks before Screening. This is a diagnostic biopsy to demonstrate 
the histopathology of the tumor, and resection of tumor is not to be performed (Section 1.3). 
Patients will receive 6 once weekly intravesical instillations of study treatment. The first 
instillation will be performed at the investigative site and subsequent instillations will be 
performed at the patient’s home by a properly trained and qualified home health professional. 
The home health professional will call the patient 1 day (+1 day) after each home instillation of 
study treatment to monitor for safety (Section 1.3).  
The UGN-102 concentration to be used in this study will be 1.33 mg mitomycin per 1 mL 
admixture. The volume of UGN-102 admixture to be instilled will be 56 mL (75 mg of 
mitomycin) (Section 7.1.3). 
At each home instillation visit, the patient and home health professional will complete a 
feasibility questionnaire. In addition, the patient and investigator will complete a feasibility 
questionnaire at the 3-month Visit (EOS) or ET Visit (Section 1.3 and Section 9.9). 
Patients will return to the clinic for the 3-monthVisit (7 weeks ± 1 week after the final instillation 
of UGN-102) for determination of response to treatment.  
Response to study treatment will be determined based on visual evaluation by cystoscopy (white 
light) (appearance, number, and size of any remaining lesions), interpretation of urine cytology, 
and for cause biopsy and histopathology of any remaining lesions (Section 9.2.2). Any lesions or 
suspect tissue must be biopsied to evaluate for persistence of disease. 
If an unscheduled visit is required during the study, assessments should be performed as 
appropriate to the needs of the visit. 


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Safety will be evaluated based on vital signs, physical examination, laboratory assessments, and a 
review of AEs. All safety data will be reviewed on an ongoing basis by the Sponsor, including close 
review and follow up of any unexpected AE assessed as related to UGN-102 (Section 9.4.1.3.3), 
and qualified per National Cancer Institute Common Terminology Criteria for Adverse 
Events (CTCAE) as Grade 3 or 4 (Section 9.4.1.3.1). 
A patient will be considered to have completed the study if the patient completes the 3-month 
Visit in accordance with the Schedule of Activities (SoA) (Section 1.3). 
Following the 3-month Visit, all patients will exit the study and continue with standard of care 
according to their treating physician. 
End-of-study is defined as the LPLV. The EOS will be declared after all patients have completed 
the 3-month Visit.  
4.2. 
Scientific Rationale for Study Design 
UroGen estimates that LG IR NMIBC represents approximately 25% of newly diagnosed 
bladder cancer cases in the United States (SEER Program, 2019). While TURBT remains the 
current surgical standard of care for treatment of LG IR NMIBC (NCCN, 2020, Chang et al, 
2016), Study BL005 (OPTIMA II) showed a favorable efficacy and safety profile with 6 once 
weekly intravesical instillations of UGN-102 (75 mg mitomycin) as an alternative to surgery, and 
demonstrated durable clinical response in patients with LG IR NMIBC (Huang et al, 2020).  
Intravesical instillation of UGN-102 may become a viable alternative to TURBT for these 
patients and is under evaluation in a Phase 3 study (BL006). One of the benefits of UGN-102 is 
the ability to safely administer in the outpatient setting by personnel trained in bladder 
catheterization with appropriate physician oversight. This study aims to demonstrate that home 
instillation of UGN-102 is a feasible alternative to instillation in a clinical setting, which might 
mitigate some of the challenges in the patient experience (logistical, expense, and comfort) when 
receiving treatment for LG IR NMIBC. 
The COVID-19 pandemic has created an unprecedented need to re-evaluate the entirety of global 
healthcare and specifically the cancer care delivery system. Home instillation of antitumor therapy 
is not new outside the US, and internationally approximately 5%-10% of patients diagnosed with a 
range of cancers receive antitumor therapy at home (Lal et al, 2013; Luthi et al, 2012; Innominato 
et al, 2016). This global practice could be considered a model for feasibility in the US for in-home 
antitumor therapy delivery. Pointedly so during an unprecedented time when in-home consultation 
and care are increasingly sought, becoming familiar to patients, and recognizably viable by both 
the patient and the healthcare provider; all thereby, mitigating increased risk of morbidity and 
mortality from COVID-19 and other readily transmissible infectious diseases (Handley and 
Bekelman, 2019; Handley et al, 2020; Laughlin et al, 2020; Dai et al, 2020).  
A re-evaluation of in-home delivery of cancer treatments in the US is not only a reasonable task 
during the current pandemic, but a potential viable option for post-pandemic practice leading to 
care that benefits the overall health, well-being and safety of patients diagnosed with certain 
cancers. Intravesical catheterization delivery of immunotherapy has been performed by trained 
medical professionals for superficial bladder cancer for over 45 years (Fuge et al, 2015). Thus, 
the procedure is foundational and having the flexibility to receive treatment by a trained and 
qualified home health professional at home may change the landscape of LG NMIBC treatment. 


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Further, feasibility for in-home treatment instillation of UGN-102 may be tested in this 
subpopulation of cancer patients given that LG IR NMIBC has a well-understood clinical 
behavior over time (Marcq et al, 2019; Hurle et al, 2018; Tiu et al, 2014) and the recent 
promising results of the OPTIMA II trial (Huang et al, 2020).  
4.3. 
Justification for Dose  
The UGN-102 dose of 75 mg was chosen based on both efficacy and tolerability. Study BL003 
demonstrated a numerically higher CRR for the 75 mg dose than for the 37.5 mg dose. In Study 
BL004, 120 mg of UGN-102 had a similar response rate and a higher rate of AEs than the 75 mg 
dose in Study BL003. Study BL005 showed a favorable efficacy and safety profile with 6 once 
weekly instillations of 75 mg UGN-102. Results showed a considerable treatment response with 
encouraging durability. The overall safety profile of UGN-102 was favorable, with primarily 
mild to moderate AEs, no treatment-related SAEs or hospitalizations, low number of treatment 
discontinuations, and no clinically meaningful trends or pattern of changes identified in 
laboratory parameters, vital signs, or physical examinations. 
4.4. 
End-of-Study Definition 
EOS will be declared after all patients have completed the 3-month Visit (7 weeks ± 1 week after 
the final instillation of UGN-102). 
The EOS is defined as LPLV. 
5. 
Study Population 
Adult patients with LG IR NMIBC who are willing to undergo study treatment at home will be 
enrolled in the study.  
5.1. 
Inclusion Criteria 
Patients are eligible to be included in the study only if all the following criteria apply: 
1. Capable of giving written informed consent which includes compliance with the 
requirements and restrictions listed in the ICF and in this protocol. 
2. Patient must be ≥ 18 years of age, at the time of signing the ICF. 
3. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed 
by cold cup biopsy at Screening or within 8 weeks before Screening. 
4. Has IR disease, defined as having 1 or 2 of the following: 
• presence of multiple tumors. 
• solitary tumor > 3 cm. 
• recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at 
the initial Screening Visit). 
5. Negative voiding cytology for HG disease within 6 weeks before Screening. 


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6. Has adequate organ and bone marrow function as determined by routine laboratory tests 
as below: 
• Leukocytes ≥ 3,000/μL (≥ 3×109/L). 
• Absolute neutrophil count ≥ 1,500/μL (≥ 1.5×109/L). 
• Platelets ≥ 100,000/μL (≥ 100×109/L). 
• Hemoglobin ≥ 9.0 g/dL. 
• Total bilirubin ≤ 1.5 × ULN. 
• AST/ALT ≤ 2.5 × ULN. 
• ALP ≤ 2.5 × ULN. 
• eGFR ≥ 30 mL/min. 
7. Has no evidence of active urinary tract infection at the Screening and baseline visits. 
8. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) 
by an appropriately trained home health professional. 
9. Contraceptive use by men and women should be consistent with local regulations regarding 
the methods of contraception for clinical study participants. Women of childbearing 
potential (defined as premenopausal women who have not been sterilized), including 
female patients and female partners of male patients, must be willing to use 2 acceptable 
forms of effective contraception from first instillation through 6 months post treatment. 
Acceptable methods of birth control that are considered to have a low failure rate (ie, less 
than 1% per year) when used consistently and correctly include implants, injections, 
combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only 
hormonal), condoms with spermicide, sexual abstinence, or vasectomized partner. 
10. Has an anticipated life expectancy of at least the duration of the trial. 
5.2. 
Exclusion Criteria  
Patients are excluded from the study if any of the following criteria apply: 
1. Received BCG treatment for UC within previous 1 year. 
2. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years. 
3. Known allergy or sensitivity to mitomycin that in the Investigator’s opinion cannot be 
readily managed. 
4. Clinically significant urethral stricture that would preclude passage of a urethral catheter 
5. History of: 
• neurogenic bladder. 
• active urinary retention. 
• any other condition that would prohibit normal voiding. 


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6. Past or current T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent 
UTUC. 
7. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the 
Investigator, the patient would be unable to comply with the protocol. 
8. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years 
except for a single dose of chemotherapy immediately after any previous TURBT. 
9. Has participated in a study with an investigational agent or device within 30 days of 
enrollment. 
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the study but are not enrolled 
or started on study treatment. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure patients to meet the Consolidated Standards of Reporting 
Trials publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAEs. 
Re-screening of patients is allowed in this study. 
5.5. 
Strategies for Recruitment and Retention  
A sufficient number of patients will be screened to ensure that approximately 10 patients with 
LG IR NMIBC are enrolled in the study. Patients who discontinue before the EOS Visit may be 
replaced at the Sponsor’s discretion. The study will be conducted at approximately 5 investigative 
sites in the US that provide care to patients with bladder cancer. 
5.6. 
Criteria for Temporarily Delaying Administration of Study 
Treatment  
If at any time during the study the Investigator identifies myelosuppression, evidence of an 
active UTI, or any other significant clinical event or laboratory derangements outside the pre-
defined parameters, treatment may be postponed for up to 4 weeks until the clinical event 
resolves and/or laboratory values improve (Section 9.3.3.1).  


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6. 
Qualified Health Care Personnel 
The study will be conducted by appropriately trained urologists, clinical nurse educators (CNEs), 
and qualified home health professionals. 
6.1. 
Clinical Nurse Educators 
This study will contract CNEs to train pharmacy personnel on study treatment preparation and 
study personnel (eg, investigators and home health professionals) on the UGN-102 instillation 
procedure. The role of the CNE in the current study will include, but may not be limited to: 
• conduct training on UGN-102 instillation procedures for the Principal Investigator, 
sub-investigator(s), home health professionals, and other relevant personnel before the 
first study treatment administration. 
• be present for training purposes during the first study treatment administration. 
• conduct training for pharmacy personnel on UGN-102 study treatment preparation as per 
the Instructions for Pharmacy.  
• following training, attend the first pharmacy preparation, if allowed by the pharmacy. 
• attend at least the first study treatment administration at the patient’s home. 
6.2. 
Home Health Professionals 
This study will contract licensed home health professionals to administer the study treatment at 
the patient’s home for Treatment Visits 2 to 6. The role of the home health professional at each 
home visit will include, but may not be limited to: 
• communicate with site study team and coordinate patient’s home visits for study 
treatment administration.  
• attend the patient’s first treatment at the investigational study site. 
• attend the patient’s home for subsequent instillations per training. 
• coordinate study drug and study supplies to be available at the patient’s home for home 
administration. 
• conduct a clinical assessment, measure vital signs, and document the findings in the 
electronic Case Report Form (eCRF). 
• review concomitant medications. 
• review adverse events and monitor patient for AEs for at least 60 minutes post-instillation. 
• call the patient approximately 24 hours after instillation to see how the patient is feeling 
and if there are any reported adverse events. 
• remove all study-related hazardous waste from the patient’s home at the end of the 
home visit. 


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7. 
Study Treatment 
Study treatment is defined as any investigational products (IPs) or marketed product(s) intended 
to be administered to a study patient according to the study protocol. 
7.1. 
Study Treatment Administered 
7.1.1. 
Study Treatment Description  
The UGN-102 admixture for intravesical instillations contains mitomycin 75 mg in 56 mL 
admixture (1.33 mg mitomycin per 1 mL). The UGN-102 admixture is prepared in advance of 
use by the pharmacy, and it is stable for up to 48 hours before administration at room 
temperature (this time is supported by in-use stability data for up to 48 hours) plus 1 additional 
hour in ice to facilitate instillation. For Treatment Visits 2 to 6, the assigned courier will obtain 
the prepared UGN-102 admixture from the site’s pharmacy and deliver it to qualified home 
health professional at the patient’s home for instillation.  
The UGN-102 single dose carton contains the below listed components (Table 1). 
Table 1 
UGN-102 Components 
Component 
Quantity (per single 
dose carton) a 
Function 
Mitomycin for Solution (vial) 
2 × 40 mg  
Active Ingredient 
Sterile Hydrogel (vial)  
1 × 60 mL 
Vehicle 
UGN-102 Admixture Labels 
3 
Admixture labels 
Instructions for Pharmacy 
1 
Instructions for admixture 
Instructions for Administration 
1 
Instructions for instillation 
WFI = water for injection. 
a 
For the proposed indication, each 40 mg vial of mitomycin will be mixed with 3 mL sterile WFI and 27 mL 
sterile hydrogel. A total of 56 mL of the 1.33 mg/mL admixture will be instilled in each patient. The hydrogel 
and mitomycin excess included are to allow for the required UGN-102 volume withdrawal from the vials. 
Refer to Figure 1 for the chemical structure of Mitomycin. 
Figure 1 
Structure of Mitomycin, USP 
 
USP = United States Pharmacopeia. 
 


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Chemical name: 7-amino-9α-metho3xymitosane 
Formula: C15H18N4O5 
Molecular weight: 334.33 g/mol 
CASRN: 50-07-7 
The vials of 40 mg mitomycin for solution are manufactured for UroGen Pharma Ltd., 9 
Ha’Ta’asiya Street, Ra’anana, Israel, by 
 
 Mitomycin is provided as a dry lyophilized powder in 
100 mL vials and will be stored at 20°C to 25°C (68°F to 77°F) with excursions permitted 
between 15°C to 30°C (59°F and 86°F) and not to exceed 40°C (104°F). 
The contents of each mitomycin for solution vial are listed in Table 2. 
Table 2 
Vial Composition of Mitomycin for Solution 
Component 
Quantity (mg per vial) 
Pharmaceutical Grade 
Function 
Mitomycin 
40 mg 
USP 
Active ingredient 
Mannitol 
80 mg 
USP 
Bulking agent 
USP = United States Pharmacopeia. 
The 60 mL of sterile hydrogel in a 100-ml glass vial are manufactured for UroGen Pharma Ltd., 
9 Ha’Ta’asiya Street, Ra’anana, Israel, by 
 
 Sterile hydrogel is provided in a 100-mL glass vial and will be stored at 
20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F and 86°F) 
and not to exceed 40°C (104°F) (Refer to Label for Hydrogel Vial). 
The contents of each sterile hydrogel vial are a proprietary mixture of poloxamer 407, 
hydroxypropyl methyl cellulose, polyethylene glycol, and water for injection. 
The components of UGN-102 are produced under aseptic conditions and according to current 
Good Manufacturing Practice (GMP) (European Commission, May 2003 Guidelines). The 
UGN-102 lots to be used in this study are tested and released under supervision and approval by 
the Sponsor or Sponsor’s Designee. 
7.1.2. 
Preparation and Administration Ancillary Supplies 
Ancillary supplies used to prepare and administer the study treatment are detailed in the 
Instructions for Pharmacy and Instructions for Administration. Home health professionals will 
also be provided with a carrying bag containing commercially available ancillary items necessary 
for home instillation of study treatment as detailed in the Study Distribution Manual. 
7.1.3. 
Administration and Dosing 
7.1.3.1. 
Administration 
Patients will receive 6 once weekly intravesical instillations of study treatment.  
Treatment Visit 1 will occur at the investigative site and study treatment instillation will be 
performed by a qualified physician. 




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Each shipment of IP supplies for the study will contain at minimum, a shipment form describing 
the content of shipment. This form will assist in maintaining current and accurate inventory 
records. When a shipment is received, the appropriate site personnel will acknowledge receipt of 
the IP supply. 
Unused UGN-102 must be available for verification by the Sponsor’s site monitor during on-site 
monitoring visits. Unused or expired UGN-102 returned to the Sponsor must be documented on 
the drug return form. 
The Investigator agrees to neither dispense the study treatment from, nor store it at, any site other 
than the site agreed upon with the Sponsor. 
Unusable UGN-102 single dose cartons will be marked “not for use” in pen over the label and 
stored separately from usable UGN-102 single dose cartons.  
Replacement UGN-102 will be supplied after request for additional supplies has been issued to 
the Sponsor’s Designee. 
Following completion of drug accountability by the clinical research associate, used study 
treatment vials should be discarded locally according to local institution guidelines for cytotoxic 
waste destruction. Discarding/destruction of the used UGN-102 admixture vials must be 
documented in the drug disposal form.  
7.2.2. 
Formulation, Appearance, Packaging, and Labeling 
The formulation of the study treatment and the contents of UGN-102 is described in 
Section 7.1.1. All clinical supplies will be packaged and labeled in compliance with GMP 
guidelines. All information regarding study treatment provided will be appropriately documented 
(ie, batch records, Certificate of Analysis, etc.). The original product packaging will be used in 
the study (UroGen Pharma Ltd., Israel). 
7.2.3. 
Product Storage and Stability 
UGN-102 single dose carton must be stored at a controlled temperature of 20°C to 25°C (68°F to 
77°F), excursion permitted between 15°C and 30°C (59°F and 86°F). Exposure to excessive heat 
(over 40°C, 104°F) should be avoided. 
The clinical supplies storage area at the investigative site must be monitored by the site staff for 
temperature consistency with the acceptable storage temperature range as specified on the label. 
Documentation of temperature monitoring should be maintained and available for review. 
7.2.4. 
Admixture 
The UGN-102 admixture (sterile hydrogel mixed with mitomycin) is stable for 48 hours at 20°C 
to 25°C (68°F to 77°F), excursion permitted between 15°C and 30°C (59°F and 86°F). Exposure 
to excessive heat (over 40°C, 104°F) should be avoided. Up to 1 hour before administration, the 
admixture should be cooled down to between -3°C (27°F) and +5°C (41°F) in order to liquify the 
UGN-102. The elapsed cooling time must be documented, which includes the length of time at 
room temperature, as well as length of time in ice. 


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7.2.5. 
Product Quality Complaint Handling 
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or 
packaging; ie, any dissatisfaction relative to the identity, quality, durability, or reliability of a 
product, including its labeling or packaging integrity. In such cases, and also in cases of 
temperature deviation, either during transport, storage, or preparation at the pharmacy, or during 
transport to patient’s home, the Investigator is responsible for notifying the Sponsor about the 
defect/temperature deviation. Any PQCs must be reported to the Sponsor/Sponsor Designee 
using: 
 or 
. 
Reporting must be done upon first awareness, and the site should await the Sponsor’s decision 
regarding the drug’s validity before drug dispensing. 
If the PQC is associated with an SAE, the investigational staff must report the PQC to the 
Sponsor/Sponsor Designee as described above and the SAE(s) must be reported according to 
Section 9.4.6 (Serious Adverse Event Reporting). The affected study products must be 
quarantined and marked “not for use” during investigation until a decision has been made 
regarding the drug’s usability. 
Product quality complaints may have an impact on the safety and efficacy of the product. Timely, 
accurate, and complete reporting and analysis of PQC information from clinical studies are 
crucial for the protection of patients, Investigators, and the Sponsor, and are mandated by 
regulatory agencies worldwide. The Sponsor has established procedures in conformity with 
regulatory requirements worldwide to ensure appropriate reporting of PQC information; all 
clinical studies conducted by the Sponsor or its affiliates will be conducted in accordance with 
those procedures. 
7.3. 
Study Intervention Compliance 
The study treatment will be administered at the investigative site or in the patient’s home by 
properly trained and qualified health care personnel. Each drug administration (including date, 
time, volume administered) will be documented in the patient’s file and eCRF (Section 7.1.3.1). 
7.4. 
Dose Modification 
Not applicable. 
7.5. 
Continued Access to Study Intervention after the End of the Study 
No study treatments will be administered to patients after the patient exits from the study. 
7.6. 
Treatment of Overdose 
Not applicable. 


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7.7. 
Past/Concomitant and Prohibited Therapy 
Any concomitant medication (including prescription or over-the-counter medications) that the 
patient is receiving at the time of enrollment or receives during the study and any past therapy 
(eg, pharmacological or surgical interventions) related to urothelial carcinoma must be recorded 
in the eCRF along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Route of administration 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. 
Prohibited concomitant medications include: 
• Systemic chemotherapy 
• Intravesical chemotherapy 
• Immunotherapy for bladder cancer treatment including but not limited to BCG 
• Pre-operative non-study chemotherapy  
In cases of symptomatic UTI, the patient will be treated with a course of antibiotics, and study 
treatment will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of 
prophylactic antibiotics and postponement of study treatment is left to the discretion of the PI or 
qualified designee. 
The Sponsor Medical Monitor should be contacted if there are any questions regarding prior or 
concomitant therapy. 
7.7.1. 
Rescue Medicine 
No rescue therapy is planned for this study. 


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8. 
Discontinuation of Study Treatment and Patient 
Discontinuation/Withdrawal 
8.1. 
Discontinuation of Study Treatment 
Discontinuation from study treatment does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol (ie, 3-month 
Visit). If a clinically significant finding is identified (including, but not limited to, changes from 
baseline) after enrollment, the Investigator or qualified designee will determine if any change in 
patient management is needed. Any new clinically relevant finding will be reported as an AE. 
8.1.1. 
Temporary Withholding of Study Treatment  
If at any time during the study the Investigator identifies clinically significant myelosuppression, 
evidence of an active UTI, or any other significant clinical event or laboratory derangements 
defined by the parameters below, treatment may be postponed for up to 4 weeks until the clinical 
event resolves and/or laboratory values improve (Section 9.3.3.1): 
• Absolute neutrophil count ≤ 1,000/μL (≥ 1.0×109/L). 
• Platelets ≤ 80,000/μL (≤ 80×109/L). 
• AST/ALT ≥ 5 × ULN. 
• Laboratory evidence of active UTI. 
8.1.2. 
Rechallenge 
No change in dose will be performed for patients who re-initiate their study treatment after 
temporary withholding (Section 8.1.1).  
8.1.3. 
Withdrawal of Consent for Home Instillation of Study Treatment 
If the patient withdraws consent for in-home instillation of study treatment, the patient may 
continue treatment and all scheduled assessments at the investigative site.  
8.2. 
Patient Discontinuation/Withdrawal from the Study  
A patient in this study may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, or compliance 
reasons. 
A patient will be considered to have withdrawn from the study for any of the following: 
• Withdrawal of consent 
• Lost to follow-up 
• No longer being followed at the Investigator’s discretion 
• Protocol non-compliance 
• Pregnancy  


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• Patient experienced an AE that led to study discontinuation 
• Death 
• Study is closed or terminated by the sponsor 
The reason for patient discontinuation or withdrawal from the study will be recorded on the eCRF. 
At the time of early discontinuation from the study, if possible, an ET Visit should be conducted 
as shown in the SoA. See Section 1.3 for data to be collected at the time of early discontinuation 
and for any further evaluations that need to be completed. The patient will be permanently 
discontinued both from the study treatment and from the study at that time. 
8.3. 
Lost to Follow-up 
A patient will be considered lost to follow-up if he or she fails to be available for 2 sequential 
scheduled home instillation visits and is unable to be contacted by the investigative site staff.  
The following actions must be taken if a patient fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain if the patient wishes to and/or should continue in the study. 
• Before a patient is deemed lost to follow-up, the Investigator or designee will make every 
effort to regain contact with the patient (where possible, 3 telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the patient’s study file.  
Should the patient continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 


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9. 
Study Assessments and Procedures 
Adherence to the study design requirements, including those specified in the SoA (Section 1.3), 
is essential and required for study conduct. 
All Screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The Investigator will maintain a Screening log to record details of all 
patients screened and to confirm eligibility or record reasons for Screening failure, as applicable. 
Procedures conducted as part of the patient’s routine clinical management (eg, blood count) and 
obtained before signing of the ICF may be utilized for Screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA (Section 1.3). 
9.1. 
Study Assessments and Procedures by Visit 
See the SoA in Section 1.3 for the timing and schedule of all study procedures and assessments.  
If an unscheduled visit is required during the study, assessments should be performed as 
appropriate to the needs of the visit. 
9.2. 
Efficacy Assessments 
Efficacy will be assessed at the 3-month Visit.  
9.2.1. 
Measurements for Evaluation of Response at 3-month Visit 
Assessment of response will be based on the following: 
• Visual observation (white light cystoscopy) 
• Biopsy of remaining lesions, if applicable (non-complete response [NCR] or 
suspected tissue) 
• Voiding urine cytology 
9.2.2. 
Evaluation of Treatment Response at 3-month Visit (Disease Assessment) 
Patient response will be evaluated according to the following criteria: 
• CR: A patient will be considered to have had CR if there is no detectable disease (NDD) 
at bladder. To determine NDD, the following conditions should be fulfilled: 
1. If visual assessment indicates no remaining tumors and urine cytology is not 
consistent with the presence of UC, the patient has NDD and CR.  
2. If any remaining lesions appear, even if they appear necrotic, the physician should 
biopsy the lesion(s). If histopathology is negative, the patient should be classified as 
having CR; if positive for cancer, the patient should be classified as NCR. 


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• NCR: A patient will be considered to have had NCR if there is evidence of disease 
under study: 
1. If tumors are still visible, all remaining lesions should be biopsied for histopathology 
and viability assessment. If histopathology still indicates cancer, then the patient is 
considered NCR. Note that biopsy results showing papillary urothelial neoplasm of 
low malignant potential are not considered cancer and in such cases the patient would 
be considered CR. 
• If evidence of disease is identified, patients will be staged according to the 
Tumor-Node-Metastases classification and graded according to the 2004 World Health 
Organization classification of tumors. Any noted progression of tumor in terms of 
transition to high grade, muscle invasion, distant disease (local assessment) will be 
documented by the site in the eCRF. 
• In the rare event that the bladder is free of tumor endoscopically, but the cytology is 
consistent with UC, the urine cytology should be repeated. Note that atypical cells 
identified on urine cytology are not consistent with LG NMIBC, and that abnormal urine 
cytology findings require clinical context to support interpretation, particularly in the 
presence of a normal cystoscopy.  
1. If the repeat urine cytology is consistent with UC, the Investigator is required to 
exclude UC of the upper tract and occult carcinoma of the bladder or urethra.  
2. If UTUC is confirmed, the patient will be considered as CR for LG NMIBC. If 
UTUC is not confirmed, the Investigator must perform random bladder biopsies to 
examine the following 6 bladder mucosal sites: bladder floor, right wall, left wall, 
dome, posterior wall, and prostatic urethra (in males) or bladder neck (in females). 
3. If histopathology is negative, the patient should be classified as having CR; if positive 
for cancer, the patient should be classified as NCR. 
9.2.3. 
Pathological Evaluation 
Biopsies and urine cytology specimens obtained at Screening or any other visit should be 
evaluated by the local laboratory (pathologist) facility. Pathology reports from local laboratory 
facilities will be provided to Investigators. 
9.3. 
Safety Assessments 
The safety of study treatment will be assessed by the following: 
• Evaluation (frequency, seriousness, severity, and type) of AEs including adverse events 
of special interest (AESIs) 
• Changes from baseline in laboratory values and incidence of measurements defined as 
potentially clinically significant  
• Clinically meaningful changes in physical examination findings including vital signs. 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 


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9.3.1. 
Physical Examinations 
A full physical examination will be performed at the Screening Visit by a physician at the 
investigative site. A urological examination will be performed at the Screening Visit, Treatment 
Visit 1, and at the 3-month Visit (or ET) by a physician at the investigative site. The 
examinations to be performed are summarized in Table 3. Additional full physical examinations 
or urological examinations may be performed during the study if clinically indicated. 
A clinical assessment will be performed before study drug instillation. Abnormal findings 
observed at home instillation visits will be documented and reported by the home health 
professional to the investigative site during the visit. 
The patient’s height and body weight will be measured during Screening. 
Table 3 
Physical Examinations 
General/Full Physical 
Examination 
Urology-Oriented Physical 
Examination a 
Clinical Assessment before 
study drug instillation 
General appearance 
Cardiovascular system 
Respiratory system 
HEENT (head, eyes, ears, 
nose, and throat) and neck 
Abdomen 
Extremities 
Neurologic system 
Skin 
Urethral meatus 
Perineal skin and mucus 
membranes 
Scrotum and testes (for male 
patients) 
Lymphadenopathy 
Rectal examination (Screening 
visit only) 
Bimanual examination (female 
patients – Screening visit only) 
General appearance 
Urethral meatus 
ET = early termination. 
a. 
Performed before cystoscopy at relevant visits. 
9.3.2. 
Vital Signs 
At each visit, the following vital signs measurements are to be taken: body temperature, 
pulse rate, respiratory rate, and blood pressure. 
Blood pressure and pulse rate measurements will be assessed in a seated position with a 
completely automated device. Manual techniques will be used only if an automated device is not 
available. 
9.3.3. 
Clinical Safety Laboratory Assessments 
Samples for hematology and serum chemistry assessments will be collected according to the 
SoA in Section 1.3 and tested at the local laboratory. The parameters to be analyzed are listed in 
Table 4. Other parameters that are part of the local laboratory standard panel may be reported in 
addition to the protocol-specified parameters. 


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Table 4 
Laboratory Safety Assessments 
Liver Function Tests: 
AST 
ALT 
GGT 
ALP 
Total bilirubin 
Direct bilirubin 
Albumin 
Total protein 
Kidney Function Tests: 
Creatinine 
Blood urea nitrogen 
Uric acid 
Sodium 
Potassium 
Bicarbonate 
Chloride 
eGFR (calculated in EDC) 
Hematology Tests: 
CBC, including red blood cell indices 
and white blood cell differential 
Platelet count 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; 
EDC = electronic data capture; eGFR = estimated glomerular filtration rate; GGT = gamma-glutamyltransferase. 
Note: Laboratory samples will be kept per storage requirements as stated in the laboratory manual until shipped to the local 
laboratory for analysis. 
The Investigator must review the laboratory report, document this review, and record any 
laboratory abnormalities as clinically significant or not clinically significant. Any clinically 
significant changes should have a corresponding AE reported. The laboratory reports must be 
filed with the source documents. 
Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant unless judged by the Investigator to be more severe than expected for the 
patient’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study (eg, in case of either temporary discontinuation) or within 4 weeks after the last 
administered dose of study treatment (ie, in case of permanent discontinuation) should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the Investigator or medical monitor. 
If any clinically significant or other values do not return to normal/baseline within a period of 
time judged reasonable by the Investigator, the etiology should be identified, and the Sponsor 
notified. 
All protocol-required laboratory tests, as defined in Table 4, must be conducted in accordance 
with the laboratory manual and the SoA (Section 1.3). 
A local laboratory will be used in this study. If laboratory values from non-protocol specified 
laboratory tests performed at the institution’s local laboratory require a change in patient 
management or are considered clinically significant by the Investigator (eg, AE), then the results 
must be recorded. 


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9.3.3.1. 
Other Significant Laboratory Derangements 
If at any time during the study the Investigator identifies clinically significant myelosuppression, 
evidence of an active UTI, or any other significant clinical event or laboratory derangements 
defined by the parameters below, treatment may be postponed for up to 4 weeks until the clinical 
event resolves and/or laboratory values improve: 
• Absolute neutrophil count ≤ 1,000/μL (≥ 1.0×109/L) 
• Platelets ≤ 80,000/μL (≤ 80×109/L) 
• AST/ALT ≥ 5 × ULN 
• Laboratory evidence of active UTI. 
9.3.4. 
Urinalysis 
At the visits specified in Section 1.3, samples will be collected for urinalysis, including culture and 
sensitivity (if indicative of infection) at the Screening Visit, and when otherwise clinically indicated. 
9.3.5. 
Pregnancy Testing 
A urine or serum pregnancy test will be conducted in female patients of childbearing potential at 
the visits specified in Section 1.3. A female is considered of childbearing potential unless: 
• At least 12 months have elapsed since the last menstrual bleeding; or 
• She is without a uterus and/or both ovaries; or 
• She has been surgically sterile for at least 6 months before study treatment administration. 
9.4. 
AEs, SAEs, and Other Safety Reporting  
The definitions of AEs and SAEs can be found in Section 9.4.1. 
AEs will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or the 
patient’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events as per instructions in Section 9.4.2 and remain responsible for following up all 
applicable AEs including those that are serious, considered related to the study treatment or 
study procedures, or that caused the patient to discontinue the study treatment or from 
participation in the study (Section 8). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 9.4.1, 
Section 9.4.5, and Section 9.4.6. 


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9.4.1. 
AEs and SAEs 
9.4.1.1. 
Definition of AE 
An AE means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 [a]; European Directive 
2001/20/EC). An AE can therefore be any unfavorable and unintended sign, symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product (“Note for Guidance on Good Clinical 
Practice” CPMP/ICH/135/95).  
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, serum chemistry, or urinalysis) or 
other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the Investigator (ie, not related to 
progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected intervention-intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
• “Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfil the definition of an AE or SAE. 
Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments, which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the patient’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the patient’s 
condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 


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• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
Any patient who reports an AE shall be examined by a doctor as soon as possible, making 
whatever intervention is necessary for the safety and well-being of the patient. All anomalies 
shall be monitored through to the patient’s recovery or clinical stabilization. Collected reportable 
AEs must be recorded in the eCRF using CTCAE version 5.0 (CTCAE, 2017) to avoid the use of 
vague, ambiguous, or colloquial expressions. The Investigator shall evaluate all collected 
reportable AEs in terms of severity and their relationship with the product being tested, 
indicating the test results and the measures to be taken. 
9.4.1.2. 
Definition of SAE  
An AE or suspected adverse reaction is considered serious if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes, at any dose:  
a. Results in death 
b. Is life-threatening 
• The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the 
patient was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the patient has been admitted (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 


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e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment should be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant medical 
events that may jeopardize the patient or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive treatment 
for allergic bronchospasm, blood dyscrasias, convulsions or development of 
intervention dependency or intervention abuse. 
9.4.1.3. 
Classification of an AE 
9.4.1.3.1. SEVERITY OF EVENT 
The severity (intensity) of an AE is to be graded by the Investigator according to CTCAE 
version 5.0 (CTCAE, 2017). 
General rules are as follows: 
1 Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
2 Moderate: minimal, local, or noninvasive intervention (eg, packing, cautery) 
indicated; limiting age-appropriate instrumental activities of daily living (ADL). 
3 Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL. 
4 Life-threatening consequences: urgent intervention indicated (SAE). 
5 Death related to AE (SAE). 
9.4.1.3.2. RELATIONSHIP TO STUDY TREATMENT (ASSESSMENT OF CAUSALITY) 
All AE/SAEs must have their relationship to study treatment/interventions and study procedures 
assessed by the clinician who examined and evaluated the patient based on temporal relationship 
and his/her clinical judgment. In a clinical study, the study product must always be suspect. 
Investigators will be asked to grade each AE/SAE as either related (a reasonable possibility of a 
relationship) or unrelated. 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study treatment administration will be 
considered and investigated. 
The Investigator is instructed to also consult the IB in his/her assessment. 
For each collected reportable AE/SAE, the Investigator is instructed to document in the medical 
notes that he/she has reviewed the AE/SAE and has provided an assessment of causality. 


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There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to the Sponsor’s Designee (via electronic data 
capture (EDC)/eCRF transmission). However, it is very important that the Investigator always 
make an assessment of causality for every event before the initial transmission of the SAE data 
to the Sponsor’s Designee (via EDC/eCRF transmission). 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
9.4.1.3.3. EXPECTEDNESS 
The Sponsor will be responsible for determining whether an AE is expected or unexpected. An 
AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the study treatment. 
An Unexpected Adverse Drug Reaction (UADR) is any noxious and unintended response that is 
related to the administration of an IP that has not been reported as expected in the IB (reference 
safety information for this study), either from previous clinical studies or the nonclinical studies. 
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is any UADR that at any dose also 
meets the criteria for SAE. 
9.4.2. 
Time Period and Frequency for Collecting AE and SAE Information 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study patient presenting for medical care, or upon review by a study 
monitor. 
Adverse events will be collected from the signing of the ICF until completion of the 3-month 
Visit (Section 1.3). Information will be captured on the appropriate eCRF including event 
description, date of onset, clinician’s assessment of severity, relationship to study treatment and 
study procedure (assessed only by those with the training and authority to make a diagnosis), and 
date of resolution/stabilization of the event. All collected reportable AEs occurring while on 
study must be documented appropriately. All collected AEs will be followed to adequate 
resolution/stabilization. 
If the study patient’s condition deteriorates at any time during the study, it will be recorded as an 
AE. AEs reported from the time of study treatment administration will be considered as 
treatment-emergent adverse events (TEAEs). 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
At study visits per the SoA (Section 1.3), the Investigator and/or designee should inquire about 
the occurrence of AE/SAEs since the last visit. The Investigator or designated investigational 
staff member should record the start date of all collected reportable events. Events will be 
followed for outcome information until resolution or stabilization and the dates of outcome must 
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All SAEs are to be recorded and reported to the Sponsor immediately and under no 
circumstance should this exceed 24 hours. The Investigator should submit any updated SAE 
data to the Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a patient has been discharged from the study, and he/she considers the event to be 
reasonably related to the study treatment or study participation, the Investigator must promptly 
notify the Sponsor within 24 hours. 
9.4.3. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrences. 
9.4.4. 
Follow-up of AEs and SAEs 
After the initial collected AE/SAE report, the Investigator and/or designee is required to 
proactively follow each patient at subsequent visits/contacts. All SAEs will be followed until 
resolution, stabilization, the event is otherwise explained, or the patient is lost to follow-up (as 
defined in Section 8.3). Further information on follow-up procedures is provided in Section 9.4.6. 
9.4.5. 
Regulatory Reporting Requirements for SAEs 
Each patient must be given a patient card containing details of the contact person at the site 
he/she should contact in case any unusual or serious signs or symptoms develop after treatment. 
Where required, patients will be examined at the center and will be clinically monitored until 
they recover. 
Expedited reporting to the Sponsor is required in the following conditions: 
1. Any SAE and follow-up SAE report, if required 
2. Death of study patient 
3. Pregnancy and outcome of the pregnancy 
The Investigator must inform the Sponsor/Sponsor Designee about the above by completing and 
submitting the SAE/Death or Pregnancy eCRF within 24 hours after its occurrence first came to 
his/her knowledge. 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of patients and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and Investigators. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 


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along with the Investigator File and will notify the IRB/IEC, if appropriate according to local 
requirements. 
Investigator safety reports must be prepared by the Sponsor for SUSARs according to local 
regulatory requirements and Sponsor policy and forwarded to Investigators as necessary. 
9.4.6. 
Serious Adverse Event Reporting 
The Investigator will immediately report to the Sponsor any SAE, whether or not considered 
study treatment-or study procedure related, including those listed in the protocol or IB and must 
include an assessment of whether there is a reasonable possibility that the study treatment or 
study procedure caused the event.  
All SAEs will be followed until satisfactory resolution or until the Investigator deems the event 
to be chronic or the patient is stable. Other supporting documentation of the event may be 
requested by the Sponsor or Sponsor’s Designee and should be provided as soon as possible. 
The Sponsor will be responsible for notifying the Food and Drug Administration (FDA) of any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in no case 
later than 7 calendar days after the Sponsor’s initial receipt of the information. In addition, the 
Sponsor must notify FDA and all participating Investigators in an Investigational New Drug 
safety report of potential serious risks, from clinical studies or any other source, as soon as 
possible, but in no case later than 15 calendar days after the Sponsor determines that the 
information qualifies for reporting. 
9.4.6.1. 
SAE Reporting Instructions 
The Investigator must inform the Sponsor within 24 hours of becoming aware of an SAE (or 
updated SAE information) by completing and submitting the SAE/Death or Pregnancy eCRF. 
It is not acceptable for the Investigator to send photocopies of the patient’s medical records to the 
Sponsor or designee in lieu of completion of the SAE/Death eCRF. 
There may be instances when copies of medical records for certain cases are requested by 
regulatory or other agencies. In this case, all patient identifiers, with the exception of the patient 
number, will be redacted on the copies of the medical records before submission to the Sponsor 
or designee. 
If a site receives a report of a new SAE from a study patient or receives updated data on a 
previously reported SAE when the electronic data capture tool has been taken off-line or is 
unavailable, then the site can report this information on a paper SAE form to the Sponsor (or 
designee) or Medical Monitor by email or telephone within 24 hours.  
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE data collection tool within the designated reporting time frames. 
The following is the contact information for SAE reporting. 
Email: 
. 
Telephone (UroGen AE Call Center): 
.  


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9.4.7. 
Pregnancy 
For any female patient who becomes pregnant while participating in the study, the Investigator 
shall immediately discontinue study treatment and ensure expedited reporting of the event within 
24 hours (Section 9.4.5). The pregnancy will be followed to term and the outcome reported. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
The patient/pregnant female partner will be followed to determine the outcome of the pregnancy. 
The Investigator will collect follow-up information on the patient/pregnant female partner and 
the neonate, and the information will be forwarded to the Sponsor. 
Any post-study pregnancy-related SAE considered reasonably related to the study treatment by 
the Investigator will be reported to the Sponsor as described in Section 9.4.5. While the 
Investigator is not obligated to actively seek this information in former study patients/pregnant 
female partner, he or she may learn of an SAE through spontaneous reporting. 
9.4.8. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs 
Not applicable. 
9.4.9. 
AESIs 
In this study, AESIs will be monitored on an ongoing basis through a regular review of adverse 
event listings. There are no requirements for the Investigator to make determination of AESIs 
and Investigators are to report all AEs in a consistent manner as described in Section 9.4.2.  
The list of AESIs is based on the most current safety profile of UGN-102 within the overall 
clinical development program and through ongoing review of emerging safety data. 
Current known AESIs include: 
• Allergic reaction to mitomycin (CTCAE Grade 3 or 4) 
• Voiding interruption due to urethral/penile edema (unrelated to prostatic hypertrophy) 
• Indication of bone marrow suppression 
• LUTS (CTCAE Grade 3 or 4) 
9.5. 
Pharmacokinetics 
Pharmacokinetic and pharmacodynamic parameters are not evaluated in this study. 
9.6. 
Genetics and/or Pharmacogenomics 
Genetics are not evaluated in this study. 


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9.7. 
Biomarkers 
Biomarkers are not evaluated in this study. 
9.8. 
Immunogenicity Assessments 
Immunogenicity is not evaluated in this study. 
9.9. 
Home Instillation Feasibility Questionnaires 
Home instillation feasibility questionnaires will be completed by the patient, the home health 
professional, and the Investigator at the following time points. 
• Patient questionnaire 
o Part 1 must be completed after home instillation of study treatment at Treatment 
Visits 2 to 6 
o Part 2 must be completed at the 3-month Visit (EOS) or ET Visit 
• Home health professional questionnaire 
o Part 1 must be completed after home instillation of study treatment at Treatment 
Visits 2 to 6 
o Part 2 must be completed after home instillation of study treatment at Treatment 
Visits 3 to 6 
• Investigator questionnaire 
o Must be completed at the 3-month Visit (EOS) or ET Visit 


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10. 
Statistical Considerations 
10.1. 
Statistical Hypotheses 
The primary objective of this study is to evaluate the feasibility of home instillation of UGN-102 
for treatment of patients with LG IR NMIBC. Analyses are descriptive and exploratory in nature 
and no formal hypothesis will be tested.  
10.2. 
Sample Size Determination 
The sample size of this study (approximately 10 patients) is based on feasibility. 
10.3. 
Analysis Set 
The Safety Analysis Set that includes all patients who received any dose of UGN-102 will serve 
as the primary population for the analyses of safety and efficacy data in this study. 
10.4. 
Statistical Analyses 
10.4.1. 
General Considerations 
All measured variables and derived parameters will be listed individually and, if appropriate, 
tabulated using descriptive statistics. For categorical variables, summary tables will be provided 
giving sample size, absolute and relative frequency, and 95% CI for proportions using the exact 
approach. For continuous variables, summary tables will be provided giving sample size, 
arithmetic mean, standard deviation, coefficient of variation (if appropriate), median, minimum 
and maximum, percentiles, and 95% CI for means of variables as appropriate.  
10.4.2. 
Primary Endpoint(s) 
The primary endpoint is to assess the feasibility of home instillation of UGN-102 by 
• Rate of home instillation discontinuations 
• Feedback questionnaires from patients, home health professional, and investigator(s) 
• Safety profile of UGN-102 as assessed through standard clinical and laboratory tests 
(hematology and chemistry, urinalysis, physical examination, vital sign measurements, 
diagnostic tests, etc.) and through the collection of reports of adverse events (AEs) and 
serious adverse events (SAEs) including AEs of special interest. 
Home Instillation Discontinuations 
Descriptive statistics will be used to summarize proportion of patients discontinuing the home 
instillations. The frequency and the percentages will be presented. 


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Feedback Questionnaire 
Patient questionnaire 
Patients will be asked to rate their home instillation experience such as comfort, safety/concerns, 
communication, preference compared to office instillation and overall experience at each home 
instillation visit after the instillation is completed. A trend in their responses will be measured 
descriptively. Patients’ home instillation recommendations will also be collected and 
summarized descriptively at the 3-month Visit/EOS or ET Visit (Appendix A). 
Home health professional questionnaire 
Home health professionals will also be asked to complete a set of questionnaires after each home 
instillation visit. Data will be summarized descriptively (Appendix B). 
Investigator questionnaire 
Investigators will be asked to provide their feedback for each patient based on the experiences of 
the patient and the home health professional(s) at the 3-month Visit/EOS or ET Visit 
(Appendix C). 
Feasibility of home instillation will be assessed based on the totality of the data. 
Adverse Events 
The incidence of TEAEs (new or worsening from baseline) will be summarized by system organ 
class and or preferred term (PT), severity (based on CTCAE grades), type of AE, relation to 
study treatment. 
Deaths reportable as SAEs and non-fatal SAEs will be listed by patient and tabulated by type of 
adverse event. 
AESIs will be considered. A comprehensive list of reported AE terms based on clinical review 
will be used to identify Medical Dictionary for Regulatory Activities (MedDRA) PTs for each of 
the AESI categories. For some events, several AE preferred terms may be ‘collapsed.’ The list of 
terms to be used for each category of adverse events of interest may be based on the Safety 
Review Team (SRT) agreements in place at the time of reporting. The SRT agreements are based 
on a review of the MedDRA dictionary. 
Summaries of the number and percentage of patients with these events will be provided for each 
type of events. Further details will be provided in the statistical analysis plan (SAP). 
Clinical Laboratory Data 
Analyses of safety laboratory data will be performed for all collected laboratory parameters. 
Laboratory data will be graded according to CTCAE version 5.0 (CTCAE, 2017), if applicable. 
In some cases (eg, white blood cell differentials), the lower limits of normal ranges used in 
CTCAE definition may need to be replaced by a clinically meaningful limit expressed in 
absolute counts. 
For laboratory tests where grades are not defined by CTCAE, results will be graded by the 
low/normal/high classifications based on laboratory normal ranges. 
Data will be summarized and/or listed separately for hematology, biochemistry, and urinary 
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Physical Examination 
Full physical examination will be performed at Screening only. Urology oriented physical 
examination will be performed at Screening, at the first treatment visit and at the EOS Visit (or 
ET Visit). Details are provided in Section 1.3 and Section 9.3.1. Any clinically relevant changes 
of urological physical examination will be recorded on the AE Sections of the eCRF and 
reported with AEs as described above. 
Vital Signs 
Table with descriptive statistics at baseline and post-baseline time points will be summarized. 
Patients exhibiting clinically notable vital sign abnormalities may be listed. 
10.4.3. 
Secondary Efficacy Endpoint(s) 
CR Rate at 3-month Visit (Disease Assessment) 
CR rate is defined as the proportion of patients who achieved CR at the 3-month disease 
assessment as determined by cystoscopy, for cause biopsy, and urine cytology. If a patient dies 
or terminates the study prior to the 3-month visit, that patient will be considered as a non-CR and 
will be included in the denominator to calculate the CR rate. CR rate will be presented along 
with Exact 95% Clopper-Pearson CIs. 
10.4.4. 
Other Analysis 
Additional exploratory endpoints may be added in the SAP. 
10.5. 
Interim Analysis 
No interim analysis will be conducted. The final analysis will be performed after all patients 
complete the end of study visit or are withdrawn from the study.  
 


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11. 
Supporting Documentation and Operational Considerations  
11.1. 
Regulatory, Ethical, and Study Oversight Considerations 
11.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, informed consent form (ICF), Investigator Brochure, and 
other relevant documents (eg, advertisements) must be submitted to an IRB/IEC by the 
Investigator and reviewed and approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study patients.  
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study patients. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of serious adverse events (SAEs) or other significant safety 
findings as required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), European Medical Device Regulation 2017/745 for clinical device 
research (if applicable), and all other applicable local regulations 
11.1.2. 
Finance and Insurance 
11.1.2.1. Finance  
The study is financed by the Sponsor as detailed in the financial agreement between the Sponsor 
and the Investigator/institution. 
11.1.2.2. Insurance 
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11.1.2.3. Consent and Other Informational Documents Provided to Patients 
Consent forms describing in detail the study treatment, study procedures, and risks are given to 
the patient, and written documentation of informed consent are required prior to initiating any 
study procedures and starting treatment/administering study treatment. The ICF is submitted with 
this protocol.  
The statement of informed consent must meet the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB/IEC or study center. 
11.1.2.4. Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Consent forms will be 
IRB-approved, and the patient will be asked to read and review the document. The Investigator 
or his/her representative will explain the nature of the study to the patient or their legally 
authorized representative and answer all questions regarding the study. A verbal explanation will 
be provided in terms suited to the patient’s comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research patients. Patients will have the 
opportunity to carefully review the written consent form and ask questions prior to signing. The 
patients should have the opportunity to discuss the study with their family or surrogates or think 
about it prior to agreeing to participate. 
Patients must be informed that their participation is voluntary and that they may withdraw from 
the study at any time, without prejudice. Patients or their legally authorized representative 
defined as per the applicable country-specific regulations will be required to sign a statement of 
informed consent prior to any procedures being done specifically for the study. 
The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the patient undergoes any study-specific 
procedures. The rights and welfare of the patients will be protected by emphasizing to them that 
the quality of their medical care will not be adversely affected if they decline to participate in 
this study. The authorized person obtaining the informed consent must also sign the ICF.  
Patients must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the patient or their legally authorized representative. 
Patients who are re-screened are required to sign a new ICF. 
11.1.3. 
Data Protection, Confidentiality, and Privacy 
Patients will be assigned a unique identifier by the Sponsor. Any patient records or datasets that 
are transferred to the Sponsor should contain the identifier only; patient names or any 
information which would make the patient identifiable should not be transferred. 
The patient must be informed that his/her personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the patient who will be required, depending on the requirements of local law, to either 
acknowledge or agree that their data may be used as described in the informed consent. 


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The patient must be informed that his/her medical/pharmacy records and records may be 
examined by Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. The 
clinical investigative site will permit access to such records. 
Patient confidentiality and privacy is strictly held in trust by the participating Investigators, their 
staff, and the Sponsor and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to patients. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study, or the data will be released to any 
unauthorized third party without prior written approval of the Sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study patient’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB, institutional policies, or Sponsor 
requirements. 
11.1.4. 
Data Review Committee 
No data review committee will be implemented for this study. 
11.1.5. 
Dissemination of Clinical Study Data 
Data collected for this study will be analyzed and stored by the Sponsor. After the study is 
completed, the de-identified, archived data will be transmitted to and stored by the Sponsor, for 
use by other researchers including those outside of the study. Permission to transmit data to the 
Sponsor will be included in the informed consent.  
When the study is completed, access to study data and/or samples will be provided through the 
Sponsor. 
11.1.6. 
Safety Oversight 
Safety oversight will be under the direction of the Sponsor. Safety will be assessed throughout 
the course of the study by the Sponsor Safety Review Team. 
11.1.7. 
Clinical Monitoring 
The Sponsor will perform on-site monitoring visits as frequently as necessary, depending on 
recruitment frequency at each site. The monitor will record dates of the visits in an investigative 
site visit log that will be kept at the site. Remote monitoring of patient Screening data will be 
performed on all patients, to ensure eligibility. The first post-initiation visit will be made as soon 
as possible (approximately 2-3 weeks) after enrollment has begun. At these visits, the monitor 
will compare the data entered into the eCRF with the hospital or clinic records (source 
documents). The nature and location of all source documents will be identified to ensure that all 
sources of original data required to complete the eCRF are known to the Sponsor and 
investigational staff and are accessible for verification by the Sponsor site contact. If electronic 
records are maintained at the investigational site, the method of verification must be discussed 
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Direct access to source documentation (medical records) must be allowed for verifying that the 
data recorded in the eCRF are consistent with the original source data. Findings from this review 
of eCRFs and source documents will be discussed with the investigational staff. The Sponsor 
expects that, during monitoring visits, the relevant investigational staff will be available, the 
source documentation will be accessible, and a suitable environment will be provided for review 
of study-related documents. The monitor will meet with the Investigator on a regular basis during 
the study to provide feedback on the study conduct. Further details of clinical site monitoring 
including handling of noncompliance issues and monitoring techniques (central, remote, or on-
site monitoring) will be provided in a Study Monitoring Plan (SMP). The SMP will describe in 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level 
of detail monitoring will be performed, and the distribution of monitoring reports. 
Independent audits may be conducted by representatives of the Sponsor’s clinical quality 
assurance department or their designee to ensure that monitoring practices are performed 
consistently across all participating sites and that monitors are following the SMP. 
11.1.8. 
Data Quality Assurance 
All patient data relating to the study will be recorded on eCRF. The Investigator is responsible 
for verifying that data entries are accurate and correct by electronically signing the CRF. 
Guidance on completion of eCRFs will be provided in the CRF Completion Guidelines. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Quality tolerance limits (QTLs) or quality control (QC) checks identify systematic issues that 
can impact patient safety and/or reliability of study results. These QTLs or QC checks (ie, data 
QC checks) will be implemented for the EDC. Any missing data or data anomalies will be 
communicated to the sites for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical study 
is conducted, data are generated, and biological specimens are collected, documented 
(ie, recorded), and reported in compliance with the protocol, ICH GCP, and applicable regulatory 
requirements (eg, Good Laboratory Practices).  
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
Study patient research data, which are for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored by the Sponsor. This will not include the patient’s contact or 
identifying information. Rather, individual patients and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by the Sponsor’s research staff will be secured and password-protected. At the 
end of the study, all study databases will be de-identified and archived by the Sponsor. 


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11.1.9. 
Data Handling and Record Keeping 
11.1.9.1. Data Collection and Management Responsibilities  
This study will use an EDC system; the designated Investigator staff will enter the data required 
by the protocol into the eCRFs. The eCRFs are built using fully validated, secure, web-enabled 
software that conforms to 21 CFR Part 11 requirements. Investigator site staff will not be given 
access to the EDC system until they have been trained. Automatic validation programs check for 
data discrepancies in the eCRFs and allow modification or verification of the entered data by the 
Investigator staff. 
Data collection is the responsibility of the clinical study staff. The Investigator is responsible for 
ensuring the accuracy, completeness, legibility, and timeliness of the data reported. It is the 
Sponsor’s expectation that data required by the protocol will be entered by the clinical site staff 
in a timely manner according to provided guidance. 
Clinical data will be entered directly from the source documents. All source documents should 
be completed in a neat, legible manner to ensure accurate interpretation of data and if applicable, 
signed or initialed and dated. 
Hard copies of the study visit worksheets may be provided for use as source document 
worksheets for recording data for each patient enrolled in the study. Data recorded in the eCRF 
derived from source documents should be consistent with the data recorded on the source 
documents. 
Data collected at home health visits will be recorded by the home health professional in the EDC.  
11.1.9.2. Study Records Retention  
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study treatment. These documents should be 
retained for a longer period, however, if required by local regulations or institutional policies. No 
records will be destroyed during the retention period without the written consent of the Sponsor, 
if applicable. It is the responsibility of the Sponsor to inform the Investigator when these 
documents no longer need to be retained. No records may be transferred to another location or 
party without written notification to the Sponsor. 
11.1.10. 
Protocol Deviations  
A protocol deviation is a departure from the study protocol and/or study related documents. The 
departure may be either on the part of the site or the patient and identified as site or patient 
deviations. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
Protocol deviations related to study inclusion or exclusion criteria, conduct of the study, patient 
management or patient assessment should be addressed in study source documents and reported 
to the Sponsor. Protocol deviations must be submitted to the local or central IRB/IEC according 
to their guidelines. The site PI/study staff is responsible for knowing and adhering to their 
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11.1.11. 
Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
11.1.12. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
patients. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the investigative site or terminate the study at 
any time for any reason at the sole discretion of the Sponsor. Investigative sites will be closed 
upon study completion. An investigative site is considered closed when all required documents 
and study supplies have been collected and an investigative site closure visit has been performed. 
The Investigator may initiate investigative site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of an investigative site by the Sponsor or Investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study treatment development 
• Determination of unexpected, significant, or unacceptable risk to patients 
• Demonstration of efficacy that would warrant stopping 
• Determination that the primary endpoint has been met 


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Protocol BL010 version 1.0 
 
57 
For site termination: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the Investigator 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs/IECs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the patient and 
should assure appropriate patient therapy and/or follow-up. 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB, and/or FDA. 
11.1.13. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
11.1.14. 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this study will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this study. The Sponsor has established policies and procedures for all study group 
members to disclose all conflicts of interest and will establish a mechanism for the management 
of all reported dualities of interest. 


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58 
12. 
References 
American Cancer Society (ACS). Cancer Facts & Figures 2020. Atlanta, GA, USA: American 
Cancer Society; 2020. 
Avallone MA, Sack BS, El-Arabi A, et al. Ten-year review of perioperative complications after 
transurethral resection of bladder tumors: analysis of monopolar and plasmakinetic bipolar cases. 
J Endourol. 2017;31(8):767-773. 
Babjuk M, Burger M, Compérat EM, et al. European Association of Urology guidelines on non-
muscle-invasive bladder cancer (TaT1 and carcinoma in situ) - 2019 update. Eur Urol. 
2019;76(5):639-657. 
Balbay MD, Cimentepe E, Unsal A, Bayrak O, Koç A, Akbulut Z. The actual incidence of 
bladder perforation following transurethral bladder surgery. J Urol. 2005;174(6):2260-2263. 
Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder 
cancer: AUA/SUO guideline. J Urol. 2016;196:1021. 
Colombo R, Rocchini L, Suardi N, et al. Neoadjuvant short-term intensive intravesical 
mitomycin C regimen compared with weekly schedule for low-grade recurrent non-muscle-
invasive bladder cancer: preliminary results of a randomised phase 2 study. Eur Urol. 
2012;62(5):797-802. 
Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. US Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute. 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf. Published November 27, 2017. Accessed July 23, 2020. 
Dai M, Liu D, Liu M, et al. Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A 
Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020;10(6):783-791.  
Daneshmand S, Patel S, Lotan Y, et al. Efficacy and safety of blue light flexible cystoscopy with 
hexaminolevulinate in the surveillance of bladder cancer: a phase III, comparative, multicenter 
study. J Urol. 2018;199(5):1158-1165. 
De Nunzio C, Franco G, Cindolo L, et al. Transuretral resection of the bladder (TURB): analysis 
of complications using a modified Clavien system in an Italian real life cohort. Eur J Surg Oncol. 
2014;40(1):90-95. 
Erikson MS, Petersen AC, Andersen KK, Jacobsen FK, Mogensen K, Hermann GG. Do repeated 
transurethral procedures under general anesthesia influence mortality in patients with non-invasive 
urothelial bladder cancer? A Danish national cohort study. Scand J Urol. 2020;54(4):281-289. 
Fuge O, Vasdev N, Allchorne P, Green JS. Immunotherapy for bladder cancer. Res Rep Urol. 
2015;7:65-79. Published 2015 May 4. 
Ghali F, Moses RA, Raffin E, Hyams ES. What factors are associated with unplanned return 
following transurethral resection of bladder tumor? An analysis of a large single institution's 
experience. Scand J Urol. 2016;50(5):370-373. 
Handley NR, Bekelman JE. The Oncology Hospital at Home. J Clin Oncol. 2019;37(6):448-452.  


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Protocol BL010 version 1.0 
 
59 
Handley NR, Bekelman JE, Binder AF. The Home is the New Cancer Center. J Natl Compr Canc 
Netw. 2020;18(10):1297-1299.  
Hollenbeck BK, Miller DC, Taub D, et al. Risk factors for adverse outcomes after transurethral 
resection of bladder tumors. Cancer. 2006;106(7):1527-1535. 
Huang W, Trainer A, Saltzstein D, Friedman B, Morris D. Can TURBT be avoided? Primary 
chemoablation with a reverse thermal gel containing mitomycin (UGN-102) in patients with low 
grade intermediate risk non-muscle invasive bladder cancer. J Urol.V. 203, No. 4S, Supplement, 
2020 (OPTIMA II) (NCT03558503). 
Hurle R, Lazzeri M, Vanni E, et al. Active Surveillance for Low Risk Nonmuscle Invasive 
Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project. J 
Urol. 2018;199(2):401-406. 
Innominato PF, Komarzynski S, Mohammad-Djafari A, et al. Clinical Relevance of the First 
Domomedicine Platform Securing Multidrug Chronotherapy Delivery in Metastatic Cancer 
Patients at Home: The inCASA European Project. J Med Internet Res. 2016;18(11):e305.  
Kamat AM, Witjes JA, Brausi M, et al. Defining and treating the spectrum of intermediate risk 
nonmuscle invasive bladder cancer. J Urol. 2014;192(2):305-315. 
Lal R, Bourayou N, Hillerdal G, et al. Home administration of maintenance pemetrexed for 
patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and 
phase II feasibility study design. Health Qual Life Outcomes. 2013;11:163.  
Laughlin AI, Begley M, Delaney T, et al. Accelerating the Delivery of Cancer Care at Home 
During the Covid-19 Pandemic. NEJM (Catalyst). 2020; Commentary.  
Lindgren MS, Bue P, Azawi N, et al. The DaBlaCa-13 Study: short-term, intensive 
chemoresection versus standard adjuvant intravesical instillations in non-muscle-invasive 
bladder cancer-a randomised controlled trial [published online ahead of print, 28 Jul 2020]. 
Eur Urol. 2020;S0302-2838(20)30541-8. 
Luthi F, Fucina N, Divorne N, et al. Home care--a safe and attractive alternative to inpatient 
administration of intensive chemotherapies. Support Care Cancer. 2012;20(3):575-581.  
Marcq G, Hénon F, Ouzaid I, Fantoni JC, Hermieu JF, Xylinas E. Active surveillance for non-
muscle invasive bladder cancer. Transl Androl Urol. 2019;8(1):54-60.  
Matulewicz RS, Sharma V, McGuire BB, Oberlin DT, Perry KT, Nadler RB. The effect of 
surgical duration of transurethral resection of bladder tumors on postoperative complications: 
an analysis of ACS NSQIP data. Urol Oncol. 2015;33(8):338.e19-24. 
Miyake M, Fujimoto K, Hirao Y. Active surveillance for nonmuscle invasive bladder cancer. 
Investig Clin Urol. 2016;57(Suppl 1):S4-S13. 
Monteiro LL, Witjes JA, Agarwal PK, et al. ICUD-SIU International Consultation on Bladder 
Cancer 2017: management of non-muscle invasive bladder cancer. World J Urol. 2019;37(1):51-60. 
Mostafid AH, Porta N, Cresswell J, et al. CALIBER: a phase II randomized feasibility trial of 
chemoablation with mitomycin-C vs. surgical management in low-risk non-muscle-invasive 
bladder cancer. BJU Int. 2020;125(6):817-826. 


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60 
National Comprehensive Cancer Network (NCCN). Bladder Cancer (Version 6.2020). 
https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Updated July 16, 2020. 
Accessed August 25, 2020. 
Patel HD, Ball MW, Cohen JE, Kates M, Pierorazio PM, Allaf ME. Morbidity of urologic surgical 
procedures: an analysis of rates, risk factors, and outcomes. Urology. 2015;85(3):552-559. 
Pereira JF, Pareek G, Mueller-Leonhard C, et al. The perioperative morbidity of transurethral 
resection of bladder tumor: implications for quality improvement. Urology. 2019;125:131-137. 
Rambachan A, Matulewicz RS, Pilecki M, Kim JY, Kundu SD. Predictors of readmission 
following outpatient urological surgery. J Urol. 2014;192(1):183-188. 
Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) 
SEER*Stat Database: Incidence - SEER 21 Regs Research Data, Limited Field Research Data + 
Hurricane Katrina Impacted Louisiana Cases, Nov 2018 Sub (2000-2016) <Katrina/Rita 
Population Adjustment> - Linked To County Attributes - Total U.S., 1969-2017 Counties, 
National Cancer Institute, DCCPS, Surveillance Research Program, released April 2019, based 
on the November 2018 submission. 
Tiu A, Jenkins LC, Soloway MS. Active surveillance for low-risk bladder cancer. Urol Oncol. 
2014;32:33.e7–33.e10.  


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Appendix A. 
Patient Questionnaire 
The purpose of this questionnaire is for you to share your experience on how you felt receiving 
UGN-102 intravesical instillation at home. Please indicate the extent to which you felt comfortable 
and safe with the treatment at home and fill in the questionnaire as per your experience. 
Part 1 
Must be completed at each home instillation visit after the instillation is completed 
 
 
Not at all 
A little 
Quite 
a bit 
Very 
much 
 
Comfort 
 
 
 
 
1. 
Were you more comfortable with today’s instillation 
at home than at your doctor’s office? 
 
 
 
 
2. 
Did you find it more difficult receiving today’s 
instillation at home than at your doctor’s office? 
 
 
 
 
 
Please explain (free text): 
3. 
Did the courtesy and caregiving of the home health 
professional make you feel comfortable? 
 
 
 
 
 
Safety 
 
 
 
 
4. 
Did you have any concerns receiving the instillation 
at home, away from the doctor’s office? 
 
 
 
 
 
Please explain (free text): 
 
Communication 
 
 
 
 
5. 
Did you receive clear and sufficient instructions on 
what to do and what to expect before the instillation? 
 
 
 
 
6. 
Did you receive clear and sufficient instructions on 
what to do and what to expect after the instillation? 
 
 
 
 
 
Preference 
 
 
 
 
7. 
Did you prefer to have today’s instillation done at 
home compared to the doctor’s office? 
 
 
 
 
 
Please explain (free text): 
 
Overall experience 
 
 
 
 
8. 
Overall are you satisfied with today’s instillation 
performed at home? 
 
 
 
 
 
Please explain (free text): 


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Protocol BL010 version 1.0 
 
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Part 2 
Must be completed at the 3-month Visit (End of Study) or Early Termination Visit 
The purpose of this questionnaire is for you to share your recommendation based on your 
experience on this study. 
1. Will you recommend home instillations of UGN-102 for other patients with non-muscle-
invasive bladder cancer (NMIBC)? 
• Yes 
• No 
Please explain (free text): 
2. Will you recommend home instillations of UGN-102 instead of having transurethral 
resection of bladder tumors (TURBT) for other patients with NMIBC? 
• Yes 
• No 
• Not applicable 
Please explain (free text): 


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Appendix B. 
Home Health Professional Questionnaire 
The purpose of this questionnaire is for you to share your experience on how you felt 
administering UGN-102 intravesical instillation at the patient’s home. Please indicate the extent 
to which you felt comfortable and safe with the treatment at the patient’s home and fill in the 
questionnaire as per your experience. 
Part 1 
Must be completed at each home instillation visit after the instillation is completed 
1. Were you comfortable performing the instillation at this patient’s home? 
• Yes 
• No 
Please explain (free text): 
2. Was it difficult to perform the instillation at this patient’s home? 
• Yes 
• No 
Please explain (free text): 
3. Did you have any concerns performing the instillation in the home setting? 
• Yes 
• No 
Please explain (free text): 
4. Did you have sufficient support performing the instillation in the home setting? 
• Yes 
• No 
Please explain (free text): 
Part 2 
Must be completed starting at the second home instillation visit (Treatment 
Visit 3 onwards) 
1. Did you perform the previous home instillation for this patient? 
• Yes 
• No 
 


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Appendix C. 
Investigator Questionnaire 
Must be completed at the 3-month Visit (End of Study) or Early Termination Visit 
The purpose of this questionnaire is to understand how comfortable and safe patients and home 
health professionals considered home instillation of UGN-102. Please answer the questions below. 
1. Was the experience of having your patient receive instillations at home more difficult, 
less difficult, or not different than having them receive instillation in your office? 
• More difficult 
• Less difficult 
• Not different 
Please explain (free text): 
2. How can we improve the overall experience (free text)? 

SAP_001.pdf: 
CONFIDENTIAL 
 
Statistical Analysis Plan: BL010 
UroGen Pharma Ltd. 
 
Version Final 1.0  
 
 
 
1 
 
Statistical Analysis Plan: BL010 
 
 Study Title: 
A Phase 3b, Open-Label, Single-Arm, Multicenter Study 
to Assess the Feasibility of Home Instillation of UGN-102 
for Treatment of Patients with Low-Grade (LG) Non-
Muscle-Invasive 
Bladder 
Cancer 
(NMIBC) 
at 
Intermediate Risk (IR) of Recurrence  
 
Study Number: 
BL010 
 
Study Phase:  
3b 
 
Sponsor: 
UroGen Pharma Ltd. 
 
 
Version  
Final 1.0 
 
 
Date: 
20 July 2023 
 
Confidentiality Statement 
This document contains confidential and proprietary information, and is not to 
be distributed to any third party. 
 
 
 
 
 


CONFIDENTIAL
Statistical Analysis Plan: BL010
UroGen Pharma Ltd.
Version Final 1.0 
2
SIGNATURE PAGE
PREPARED BY:
Author
Li Liu, PhD
Senior Statistical Consultant
____________________
UroGen Pharm, Ltd.
Signature
Date: _______________
APPROVED BY:
Approver
Brent Burger, M.S.
Senior Director, Biostatistics
____________________
UroGen Pharm, Ltd.
Signature
Date: _______________
Approver
Sunil Raju, MD
Vice President, Clinical Development
____________________
UroGen Pharm, Ltd.
Signature
Date: _______________
__________________
gnature
te: _______________

____________________
Signature
Date: _______________


____________________
Signature
Date: _______________





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Statistical Analysis Plan: BL010 
 
 
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TABLE OF CONTENTS 
PAGE 
ABBREVIATIONS .......................................................................................... 5 
1. 
INTRODUCTION ..................................................................................... 7 
2. 
STUDY OBJECTIVES AND ENDPOINTS ............................................... 7 
3. 
STUDY DESIGN ..................................................................................... 8 
3.1. 
Statistical Hypothesis ................................................................... 9 
3.2. 
Sample Size Justification ............................................................. 9 
3.3. 
Randomization and Blinding ...................................................... 10 
4. 
PLANNED ANALYSES .......................................................................... 10 
4.1. 
Interim Analyses ........................................................................ 10 
4.2. 
Final Analysis ............................................................................. 10 
5. 
ANALYSIS POPULATIONS ................................................................... 10 
6. 
TREATMENT COMPARISONS ............................................................. 10 
7. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ...................... 10 
7.1. 
Multicenter Studies .................................................................... 11 
7.2. 
Other Strata and Covariates ...................................................... 11 
7.3. 
Multiple Comparisons and Multiplicity ........................................ 11 
8. 
DATA HANDLING CONVENTIONS ...................................................... 11 
8.1. 
Premature Withdrawal and Missing Data ................................... 11 
8.2. 
Derived and Transformed Data .................................................. 12 
8.2.1. 
Reference Date ........................................................... 12 
8.2.2. 
Study Day ................................................................... 12 
8.2.3. 
Calculation of Durations .............................................. 12 
8.2.4. 
Imputation of Partial Dates .......................................... 12 
8.2.5. 
Baseline Definition ...................................................... 13 
9. 
PATIENT DISPOSITION, DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS ............................................................................. 13 
9.1. 
Disposition of Patients ............................................................... 13 
9.2. 
Protocol Deviations .................................................................... 13 
9.3. 
Demographic and Baseline Characteristics ................................ 13 
9.4. 
General Medical History and Urothelial Carcinoma Related 
Medical History (UCMH) ............................................................ 14 
9.5. 
Prior and Concomitant Medications ........................................... 14 
9.6. 
Prior and Concomitant Surgical Procedures............................... 15 
10. EFFICACY ANALYSES ......................................................................... 15 
10.1. 
Efficacy Analyses ....................................................................... 15 
10.1.1. 
Complete Response Rate (CRR) at 3-Month Visit....... 15 
11. FEEDBACK QUESTIONNAIRE ............................................................. 15 


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11.1. 
Patient Questionnaire ................................................................ 15 
11.2. 
Home Healthcare Professional (HHP) Questionnaire ................. 17 
11.3. 
Investigator Questionnaire ......................................................... 17 
12. SAFETY ANALYSES ............................................................................. 17 
12.1. 
Extent of Exposure of UGN-102 ................................................. 17 
12.2. 
Adverse Events .......................................................................... 18 
12.3. 
Deaths and Serious Adverse Events .......................................... 18 
12.4. 
Adverse Events of Special Interest ............................................ 19 
12.5. 
Clinical Laboratory Evaluations .................................................. 19 
12.5.1. 
Potentially Clinically Significant (PCS) Laboratory 
Values ......................................................................... 19 
12.5.2. 
Potentially Clinically Significant Abnormal Liver Function 
Tests ........................................................................... 20 
12.6. 
Vital Signs .................................................................................. 21 
12.6.1. 
Potentially Clinically Significant (PCS) Vital Sign 
Abnormalities .............................................................. 21 
12.7. 
General Physical Examination ................................................... 22 
12.8. 
Urology-Oriented Examination ................................................... 22 
13. PHARMACOKINETIC ANALYSES ........................................................ 22 
14. PHARMACODYNAMIC AND BIOMARKER ANALYS ............................ 22 
15. PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES .................. 22 
16. PHARMACOGENETIC DATA ANALYSES ............................................ 22 
17. REFERENCES ...................................................................................... 22 
18. APPENDICES ....................................................................................... 22 
Appendix A Patient Questionnaire ......................................................... 23 
Appendix B Home Health Professional Questionnaire ........................... 25 
Appendix C Investigator Questionnaire ................................................. 26 
Appendix D Imputation Rules for Missing or Partial Dates ..................... 26 
Appendix E Laboratory CTCAE Grade Version 5.0 Criteria ................... 30 
Appendix F Data Display Specifications ................................................ 31 
 


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ABBREVIATIONS 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic class 
BMI 
body mass index 
CI 
confidence interval 
CDISC 
clinical data interchange standards consortium 
CR 
complete response 
CRR 
complete response rate  
CSR 
clinical study report  
CTCAE 
common terminology criteria for adverse events 
DBP 
diastolic blood pressure 
eCRF 
electronic case report form 
EOS 
end of study 
ET 
early termination; 
HHP 
Home Healthcare Professional 
ICH 
International Council for Harmonisation 
IP 
investigational product 
IR 
intermediate risk  
LFT 
liver function test 
LG 
low grade 
LLN 
lower limit of the normal range 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCR 
non-complete response 
NMIBC 
non-muscle-invasive bladder cancer 
PCS 
potentially clinically significant 
PDP 
protocol deviation plan 
PT 
preferred term 
SAE 
serious adverse event 
SAP 
statistical analysis plan 


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SAS 
Statistical analysis system 
SBP 
systolic blood pressure 
SOA 
schedule of activities 
SOC 
system organ class 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TURBT 
transurethral resection of bladder tumors 
UC 
Urothelial Carcinoma 
ULN 
upper limit of the normal range 
 
 
  
 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes all planned analyses for the Clinical 
Study Report (CSR) of study BL010 (Home Instillation), a phase 3b, open-label, 
single-arm, multicenter study to assess the feasibility of home instillation of UGN-
102 for treatment of patients with low-grade (LG) non-muscle-invasive bladder 
cancer (NMIBC) at intermediate risk (IR) of recurrence.  
This SAP is written with due consideration of the recommendations outlined in the most 
recent International Conference on Harmonization (ICH) E9 Guideline entitled Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline entitled Structure and 
Content of Clinical Study Reports (CSR). The SAP is based on the following study 
documents: 
• Protocol, Version 1.0 dated 11 June 2021  
• Case report form (CRF), Version 16.4 dated 16 May 2022 
All decisions regarding final analysis, as defined in the SAP document, have been made 
prior to database lock of the study data. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
Table 1 lists the study objectives and corresponding endpoints which are under the scope 
of this SAP.  
 
Table 1 
Study Objectives and Endpoints 
OBJECTIVE 
ENDPOINT 
Primary 
 
To evaluate the feasibility of 
home instillation of UGN-102 
for treatment of patients with 
LG IR NMIBC 
Feasibility will be assessed by evaluation of:  
• Safety and tolerability  
o Reporting of AEs, including SAEs 
and AESIs  
o Standard clinical laboratory tests 
(hematology, serum chemistry, and 
urinalysis)  
o Physical examination and vital sign 
measurements.  
• Rate of discontinuation from at home study 
treatment. 
• Feedback from patients, home health 
professionals, and investigators via 
standardized questionnaires 
Secondary 
 
To evaluate the efficacy of 
UGN-102 for treatment of LG 
IR NMIBC following home 
CRR is defined as the proportion of patients who 
achieved CR at the 3-month Visit (3 months after the 


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OBJECTIVE 
ENDPOINT 
instillation with respect to 
complete response rate (CRR) 
at 
the 
3-month 
disease 
assessment 
first instillation of study treatment) as determined by 
cystoscopy, for cause biopsy, and urine cytology 
AE = adverse event; AESI = adverse event of special interest; CR = complete response; 
CRR = complete response rate; LG IR NMIBC = low-grade intermediate risk non-muscle-invasive 
bladder cancer; SAE = serious adverse event. 
 
3. 
STUDY DESIGN 
This Phase 3b, open-label, single-arm, multicenter study is designed to assess the 
feasibility of home instillation of UGN-102 (mitomycin) for intravesical solution in 
approximately 10 patients with LG IR NMIBC. 
The primary objective of this study is to evaluate the feasibility of home instillation of 
UGN-102 as an alternative to instillation in a clinical setting. Feasibility will be assessed 
by evaluation of safety and tolerability, rate of discontinuation from at home study 
treatment, and feedback from patients, home health professionals, and investigators via 
standardized questionnaires. The secondary objective of this study is to evaluate the 
efficacy of UGN-102 for the treatment of LG IR NMIBC following home instillation. 
Efficacy will be assessed at the 3-month Visit (3 months after the first instillation of UGN-
102) by CRR, defined as the proportion of patients who achieved CR as determined by 
cystoscopy, for cause biopsy, and urine cytology. 
Patients who provide informed consent will undergo a Screening Visit to determine 
eligibility. The Screening Period is up to 14 days for patients who do not need a Screening 
biopsy and up to 28 days for patients who need a Screening biopsy. Screening procedures 
are required to provide evidence of LG NMIBC and to rule out evidence of HG disease.  
 
A single representative cold cup biopsy to confirm LG tumor will be performed only if 
not already performed within 8 weeks before Screening. This is a diagnostic biopsy to 
demonstrate the histopathology of the tumor, and resection of tumor is not to be 
performed. 
 
Patients will receive 6 once weekly intravesical instillations of study treatment. The first 
instillation will be performed at the investigative site and subsequent instillations will be 
performed at the patient’s home by a properly trained and qualified home health 
professional. The home health professional will call the patient 1 day (+1 day) after each 
home instillation of study treatment to monitor for safety.  
 
The UGN-102 concentration to be used in this study will be 1.33 mg mitomycin per 1 
mL admixture. The volume of UGN-102 admixture to be instilled will be 56 mL (75 mg 
of mitomycin). 
 
At each home instillation visit, the patient and home health professional will complete a 
feasibility questionnaire. In addition, the patient and investigator will complete a 
feasibility questionnaire at the 3-month Visit (EOS) or ET Visit. 


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Patients will return to the clinic for the 3-monthVisit (7 weeks ± 1 week after the final 
instillation of UGN-102) for determination of response to treatment. 
Response to study treatment will be determined based on visual evaluation by cystoscopy 
(white light) (appearance, number, and size of any remaining lesions), interpretation of 
urine cytology, and for cause biopsy and histopathology of any remaining lesions. Any 
lesions or suspect tissue must be biopsied to evaluate for persistence of disease.
If an unscheduled visit is required during the study, assessments should be performed as 
appropriate to the needs of the visit.
Safety will be evaluated based on vital signs, physical examination, laboratory assessments, 
and a review of AEs. All safety data will be reviewed on an ongoing basis by the Sponsor, 
including close review and follow up of any unexpected AE assessed as related to UGN-
102, and qualified per National Cancer Institute Common Terminology Criteria for Adverse 
Events (CTCAE) as Grade 3 or 4.
A patient will be considered to have completed the study if the patient completes the 3-
month Visit in accordance with the Schedule of Activities (SoA).
Following the 3-month Visit, all patients will exit the study and continue with standard 
of care according to their treating physician.
End-of-study is defined as the LPLV. The EOS will be declared after all patients have 
completed the 3-month Visit. 
Figure 1: Study Schema
a. One day after every home instillation (+1 day).
3.1.
Statistical Hypothesis
No formal hypothesis will be tested.
3.2.
Sample Size Justification
The sample size of this study (approximately 10 patients) is based on feasibility. 


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3.3. 
Randomization and Blinding 
Not Applicable. 
4. 
PLANNED ANALYSES 
4.1. 
Interim Analyses 
No interim analysis is planned for this study. 
4.2. 
Final Analysis 
The final analysis will be performed after all patients complete the end of study visit or 
are withdrawn from the study.   
5. 
ANALYSIS POPULATIONS 
For the purposes of analysis, the following analysis set is defined: 
Analysis Set 
Description 
Safety Analysis Set The Safety Analysis Set includes all patients who received any dose 
of UGN-102. The Safety Analysis Set will serve as the primary 
population for the analyses of safety and efficacy data in the study.   
 
6. 
TREATMENT COMPARISONS 
Not Applicable. 
 
7. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Data will be listed and summarized according to Clinical Data Interchange Standards 
Consortium (CDISC) standards and ICH E9 Guideline. SAS software will be used to 
perform all data analyses, generate tables, figures, and listings. 
 
Unless otherwise stated, all listings will be sorted by patient identification number (ID) 
and then by visit date if applicable. 
 
Unless otherwise stated, continuous variables will be summarized with n, mean, median, 
standard deviation, minimum and maximum, and categorical variables will be 
summarized with frequency counts and percentages.  
 
Deviations from the analyses in the SAP will be identified in the CSR. 
 


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7.1. 
Multicenter Studies 
Not Applicable.  
7.2. 
Other Strata and Covariates 
Not Applicable. 
 
7.3. 
Multiple Comparisons and Multiplicity 
Not applicable.  
 
8. 
DATA HANDLING CONVENTIONS 
The following sections provide a general description of the derived and transformed 
variables used to describe and analyze the data.  Separate analysis dataset specifications 
provide full details on all data derivations and transformations including standard 
oncology algorithms.  The analysis dataset specifications will clearly communicate the 
content and source of the datasets supporting the statistical analyses.  
 
8.1. 
 Premature Withdrawal and Missing Data 
A patient will be considered to have withdrawn from the study for any of the following: 
• Withdrawal of consent 
• Lost to follow-up 
• No longer being followed at the Investigator’s discretion 
• Protocol non-compliance 
• Pregnancy 
• Patient experienced an AE that led to study discontinuation 
• Death 
• Study is closed or terminated by the sponsor 
If a patient dies or terminates the study prior to the 3-month visit, that patient will be 
considered as a NCR and will be included in the denominator to calculate the CR rate. 
 
Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument. These data will be indicated using a “blank” in patient listing 
displays. Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
 
Patients with the designation of treatment relationship for adverse events (AE) and 
serious adverse events (SAEs) missing will have the worst-case assumed to impute the 
relationship: if relationship to study treatment is missing it will be assumed to be “Yes.” 
There will be no other imputation for missing data other than what is described in 
Appendix D Imputation Rules for Missing or Partial Dates. 
 


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8.2. 
Derived and Transformed Data 
8.2.1. 
Reference Date 
There are two reference dates: 
 
• The reference date for age is the date of Informed Consent as age is an 
eligibility requirement. 
 
• The safety/efficacy reference date is the date of first instillation of UGN-102 
and will be used to calculate study day for safety/efficacy measures. 
 
8.2.2. 
Study Day  
The study day for safety and efficacy measures are the same in this study. If the date of 
interest occurs on or after the reference date, then the study day will be calculated as (date 
of interest - reference date) + 1. If the date of interest occurs before the reference date, 
then the study day will be calculated as (date of interest – reference date). There is no 
study day 0. 
 
8.2.3. 
Calculation of Durations  
Durations (e.g., duration of adverse event) will be calculated as stop date minus start date 
plus one. 
 
8.2.4. 
Imputation of Partial Dates 
In general, imputed partial dates will not be used to derive study day or duration (e.g., 
duration of adverse events). In addition, imputed dates are not used for deriving the last 
contact date. 
 
Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data in listings 
only. In addition, partial dates may be imputed for ‘slotting’ data for specific analysis 
purposes as outlined below. 
 
The partial date imputation will follow Analysis Data Model (ADaM) conventions. The 
ADaM approach is to populate the numeric date variables with the imputed date and add 
a flag variable to the dataset that indicates the level of imputation. The flag variable can 
contain the values: blank, 'D,' 'M,' 'Y.' 
 
blank: indicates that no imputation was done 
D='Day': indicates that the day portion of the date is imputed 
M='Month': indicates that the month and day portions of the date are imputed 
Y='Year': indicates that the entire date (year, month, and day) is imputed. 
 


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Details on imputing partial dates for specific datasets are outlined in Appendix D 
 
8.2.5. 
Baseline Definition 
For Safety analyses, baseline will be defined as the most recent non-missing value prior 
to the first instillation of UGN-102 i.e., prior to Day 1. 
 
9. 
PATIENT DISPOSITION, DEMOGRAPHICS AND OTHER 
BASELINE CHARACTERISTICS 
Unless otherwise stated, all tables and listings in this section will be based on the safety 
population, and display the analysis population as ‘Safety Analysis Set’. 
9.1. 
Disposition of Patients 
The number of patients screened and enrolled will be summarized.  In addition, we will 
also include patients who had at least one UGN-102 instillation and at least one home 
instillation. 
 
A summary of the number of patients in each of the analysis sets described in Section 5 
will be provided. 
 
A summary of treatment status of UGN-102 will be provided.  This display will show the 
number and percentage of patients who discontinued the treatment with the primary 
reasons for discontinuation.  Reasons for treatment discontinuation will be presented in 
the order they are displayed in the eCRF.  A listing of UGN-102 treatment discontinuation 
will be generated.   
 
A summary of patient status of study completion (completed the study versus 
withdrew/discontinued early) and reasons will be provided.  This display will show the 
number and percentage of patients who completed or withdrew from the study, and 
primary 
reasons 
for 
study 
completion/withdrawal. 
 
Reasons 
for 
study 
completion/withdrawal will be presented in the order they are displayed in the eCRF.  
The corresponding listing will also be generated.  
   
9.2. 
Protocol Deviations 
All protocol deviations will be listed and will include severity of the deviation (e.g. major 
versus minor) and the categories (e.g. eligibility criteria, protocol implementation, safety 
etc.) using the Safety population.  See the Protocol Deviation Plan (PDP) for details of 
protocol deviations. 
 
9.3. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g. age, sex, race, ethnicity, height, weight and BMI) 
will be summarized and listed. Age, height, weight and BMI will be summarized using 


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the mean, standard deviation, minimum, median (quartiles), and maximum.  Categorical 
variables including but not limited to age group (<65, ≥ 65 to <75, ≥75 to <85, ≥85 years, 
<65 years versus ≥65 years, and <75 years versus ≥75 years ), BMI category (<30 kg/m2, 
≥30 kg/m2), sex, race, ethnicity, treatment course (full course - 6 instillations, partial 
course <6 instillations), tumor size (≤3 cm, >3 cm), tumor count, visual appearance of 
the lesions, tumor grading, tumor staging, number of prior transurethral resection of 
bladder tumors (TURBT), Days since the last TURBT and previous LG NMIBC episodes 
within 1 year of the current diagnosis (Yes, No) will be summarized using counts and 
percentages. 
 
9.4. 
General Medical History and Urothelial Carcinoma Related 
Medical History (UCMH) 
Medical history, Past and Concurrent Urothelial Carcinoma (UC) Medical History 
reported terms will be coded to a SOC and PT using the most recent version of MedDRA 
dictionary version 24.0 or later. Number and percent of patients reporting any UC related 
medical history by SOC and PT for the safety analysis set will be provided. A patient 
with multiple medical conditions will be counted once per SOC and PT. For computing 
percentages, the denominator will be the number of patients in the SAFETY analysis Set. 
The summary table will be sorted by descending order of frequency of SOC (then 
alphabetically for ties), then by descending order of frequency of PT within each SOC 
(then alphabetically for ties). A patient data listing of medical history will be provided. 
 
9.5. 
Prior and Concomitant Medications 
All medications will be coded using the World Health Organization Drug Dictionary, 
WHODRUG GLOBAL C3 March 1, 2021 or later. The Anatomical Therapeutic Class 
(ATC) Level 2, Level 3 and preferred name will be used to list and summarize the data. 
Analysis of concomitant medications use will be performed in the following manner:  
• Prior medications: Any medication that were started and stopped prior to the first 
instillation of UGN-102. The number and percentage of patients reporting the use 
of prior medications by ATC Level 2, ATC Level 3 and preferred terms will be 
summarized for the SAFETY analysis set. For computing percentages, the 
denominator will be the number of patients in the SAFETY analysis set.  
• Concomitant medications: Any prior medications that are ongoing or any new 
medication administered following the first instillation of UGN-102 for patients 
in UGN-102 arm. The number and percentage of patients reporting the use of 
concomitant medications by ATC Level 2, ATC Level 3 and preferred terms will 
be summarized for the SAFETY analysis set. For computing percentages, the 
denominator will be the number of patients in the SAFETY analysis set.  
All prior and concomitant medications will be included in a data listing. 
 


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9.6. 
Prior and Concomitant Surgical Procedures 
Prior surgical procedures are surgical procedures that were done prior to the first 
instillation of UGN-102 for patients in UGN-102 arm. 
 
Concomitant surgical procedures are surgical procedures that were done following the 
first instillation of UGN-102 through end of study.  
 
All surgical procedures will be coded to a SOC and PT using the most recent version of 
the MedDRA dictionary version 23.1 or later. Concomitant surgical procedures will be 
summarized similar to that described for prior and concomitant medication in Section 
9.4.  
All prior and concomitant surgical procedures will be included in a data listing. 
10. 
EFFICACY ANALYSES 
Efficacy analyses will be based on the SAFETY population as defined in Section 5 or a 
subset of the SAFETY population as described for each analysis.   
 
Efficacy assessments are based on cystoscopy, for-cause biopsy, and cytology to assess 
response status of a patient at efficacy visit.  Investigator assessments will be considered 
as primary assessments.  
 
10.1. 
Efficacy Analyses 
10.1.1. 
Complete Response Rate (CRR) at 3-Month Visit 
Complete response rate (CRR) is defined as the proportion of patients in the SAFETY 
population who achieved CR at the 3-month disease assessment as determined by 
cystoscopy, for cause biopsy, and urine cytology. If a patient dies or terminates the study 
prior to the 3-month visit, that patient will be considered as a non-CR and will be included 
in the denominator to calculate the CR rate. 
CRR will be presented along with the exact 95% CIs. A test for binomial proportions 
(SAS PROC FREQ with binomial option) will be used to derive the exact two-sided 95% 
CI for the CRR using the Clopper-Pearson method (Clopper and Pearson, 1934). 
 
11. 
FEEDBACK QUESTIONNAIRE 
Feasibility of home instillation will be assessed based on the totality of the data. 
11.1. 
Patient Questionnaire 
Patients will be asked to rate their home instillation experience such as comfort, 
safety/concerns, communication, preference compared to office instillation and overall 
experience at each home instillation visit after the instillation is completed. A trend in 
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recommendations will also be collected and summarized descriptively at the 3-month 
Visit/EOS or ET Visit.  
 
Patients home instillation experience questionnaire responses will be summarized by 
frequency and percentages for each of the domains namely, Comfort, Safety, 
Communication, Preference and Overall Experience. For computing percentages, the 
denominator will be the number of patients in the Safety analysis set. A listing of Patient 
Questionnaire responses will also be presented. 
 
Below table has the scores for each of the questions. The higher score reflects a more 
favorable response for each of the questions. The scoring method of this questionnaire 
will consist of a calculation of a raw total score. Each of the domains like 
Comfort(Q1+Q2+Q3), Safety(Q4), Communication(Q5+Q6), Preference(Q7) and 
Overall experience score(Q8) will be calculated based on the scoring method in Table 2. 
In addition, the composite score (sum of all the eight questions scores) will also be 
calculated based on the table below. 
 
Table 2 
Scoring questionnaire responses  
 
  
Not at all  A little  Quite 
a bit  
Very 
much  
  
Comfort  
  
  
  
  
1.  
Were you more comfortable with today’s 
instillation at home than at your doctor’s office?  
 1 
 2 
 3 
 4 
2.   Did you find it more difficult receiving today’s 
instillation at home than at your doctor’s office?  
 4 
3  
2  
1  
3.  
Did the courtesy and caregiving of the home health 
professional make you feel comfortable?  
1  
2  
 3 
4  
  
Safety  
  
  
  
  
4.  
Did you have any concerns receiving the 
instillation at home, away from the doctor’s 
office?  
 4 
3  
2  
1  
  
Communication  
  
  
  
  
5.  
Did you receive clear and sufficient instructions on 
what to do and what to expect before the 
instillation?  
 1 
2  
3  
4  
6.  
Did you receive clear and sufficient instructions on 
what to do and what to expect after the instillation?  
 1 
2  
3  
4  


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Preference  
  
  
  
  
7. 
Did you prefer to have today’s instillation done at 
home compared to the doctor’s office?  
 1 
2  
3  
4  
  
Overall experience  
  
  
  
  
8. 
Overall are you satisfied with today’s instillation 
performed at home?  
 1 
2  
3  
4  
 
11.2. 
Home Healthcare Professional (HHP) Questionnaire 
Home health professionals will be asked to complete a set of questionnaires after each 
home instillation visit. Data will be summarized descriptively. HHP responses will be 
summarized by frequency and percentages. For computing percentages, the denominator 
will be the number of patients in the Safety analysis set. A listing of HHP responses will 
also be presented. 
11.3. 
Investigator Questionnaire 
Investigators will be asked to provide their feedback for each patient based on the 
experiences of the patient and the home health professional(s) at the 3-month Visit/EOS 
or ET Visit. Investigator responses will be summarized by frequency and percentages. 
For computing percentages, the denominator will be the number of patients in the Safety 
analysis set. Listing of Investigator responses will also be presented. 
 
12. 
SAFETY ANALYSES 
The primary analysis is the safety analysis to assess the feasibility of home instillation of 
UGN-102. All safety analyses will be based on the safety analysis set. 
12.1. 
Extent of Exposure of UGN-102 
Treatment exposure of UGN-102 will be categorized as follows:   
• 1 instillation of UGN-102 
• 2 instillations of UGN-102 
• 3 instillations of UGN-102 
• 4 instillations of UGN-102 
• 5 instillations of UGN-102 
• 6 instillations of UGN-102 
Categorical treatment exposure will be summarized using patient counts and 
percentages.  For computing percentages, the denominator will be the number of 
patients in the Safety analysis set. 
Descriptive statistics of UGN-102 volume (mL) and mitomycin dose (mg) instilled at 
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mg will be calculated as 1.33 mg/mL concentration of mitomycin times volume of 
UGN-102 (mL) instilled at week 1 through week 6. 
A data listing of treatment exposure will be presented. 
 
Rate of Home instillation Discontinuations: 
Any patient who discontinues from the home instillation process will be counted under 
this category. Descriptive statistics will be used to summarize proportion of patients 
discontinuing the home instillations. The frequency and the percentages will be 
presented.  For computing percentages, the denominator will be the number of patients 
in the Safety analysis set. 
12.2. 
Adverse Events 
Adverse Events (AEs) will be coded according to the latest version of the MedDRA 
dictionary version 24.0 or later.  AEs will be graded according to the CTCAE Version 
5.0. 
AEs shall be recorded starting at signing of ICF until the end of the follow-up or early 
termination. A treatment-emergent adverse event (TEAE) is defined as an AE that occurs 
on or after the day of the first instillation of UGN-102 or a pre-treatment AE that worsens 
during the study. 
An overall summary with number and percentage of patients with all AEs, all serious 
AEs (SAE), TEAEs, different TEAE categories, like treatment-related, procedure 
related, serious, serious related to treatment or procedure, leading to treatment or study 
discontinuation, fatal, and AEs of special interest (AESI) will be provided.  
AEs will be summarized by number and percentage of patients having at least one AE, 
having at least one AE in each primary system organ class (SOC) and for each preferred 
term (PT) using MedDRA coding. A patient with multiple occurrences of an AE will be 
counted only once in the respective AE category. A patient with multiple CTCAE grades 
for the same preferred term will be summarized under the maximum CTCAE grade 
recorded for the event. 
In AE summaries, the primary SOC will be presented by descending order of frequency 
in UGN-102 column (alphabetically for ties), then PTs will be sorted by descending order 
of frequency within each SOC (alphabetically for ties). The sort order for the PT will be 
based on their frequency. 
 
All AEs will be listed.   
 
12.3. 
Deaths and Serious Adverse Events 
In the event that a patient has withdrawn consent, no data after the withdrawal of consent 
date from this patient including death is supposed to appear in the database, which should 
be part of the data cleaning process. All deaths occurring any time from the time of 
informed consent to the clinical cut-off date will be listed displaying the primary cause 
of death (Adverse event, related to cancer, or other).  


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A listing for SAEs will be generated. 
 
12.4. 
Adverse Events of Special Interest  
An adverse event of special interest is a grouping of adverse events that are of scientific 
and medical concern specific to UGN-102. A comprehensive list of MedDRA terms 
based on clinical review will be used to identify each type of events. 
 
The following categories of AE of special interest will be summarized by treatment arm 
as permitted by data: 
• Allergic reaction 
• Bone marrow suppression 
• Genitourinary infections 
• Lower urinary tract symptoms 
• Voiding interruption due to urethral/penile edema (unrelated to prostatic 
hypertrophy) 
 
Additional AEs of special interest may be identified through manual review of all AEs 
by SOC and PT prior to the database lock.   
Summaries of the number and percentage of patients with these events will be provided 
by category and PT; The summary of event characteristics will also be provided, 
including number of patients with any event, number of events, number of patients with 
any event that is serious, number of patients with any event that is related to study 
treatment, the worst outcome of the event, maximum grade and the action taken for the 
event. The worst-case approach will be applied at patient level for the event outcome, 
maximum grade and the action taken, i.e. a patient will only be counted once as the worst 
case from all the events that patient had. These summaries will be provided for each type 
of AESI separately. 
 
AESIs will be flagged in the general AE listing.  
 
12.5. 
Clinical Laboratory Evaluations 
Samples for hematology, serum chemistry, and urinalysis assessments will be collected 
according to the SoA table (protocol Section 1.3) and tested at the local laboratory. 
 
12.5.1. 
Potentially Clinically Significant (PCS) Laboratory Values 
Patients with PCS laboratory values will be assessed via the incidence of patients 
meeting the PCS criteria by time point. For computing percentages, the denominator 
will be the number of patients with a post-baseline value for the specific laboratory 
parameter, except for hemoglobin that requires patients with a baseline and a post-
baseline value, and the respective time point. The PCS laboratory criteria are provided 
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Table 3: PCS Laboratory Criteria  
Laboratory Parameter 
Conventional 
Unit 
Lower Limit 
Upper Limit 
Chemistry 
Creatinine 
mg/dL 
 
>2.2 
Sodium 
mEq/L 
≤130 
>150 
Potassium 
mEq/L 
<3.0 
>5.5 
Total bilirubin 
mg/dL 
 
>1.5 × ULN 
ALT 
U/L 
 
>3 × ULN 
AST 
U/L 
 
>3 × ULN 
GGT 
U/L 
 
>2.5 × ULN 
Hematology 
Hemoglobin 
g/dL 
<0.8 × LLN and 
>20% decrease 
from baseline 
>1.3 × ULN 
and >30% 
increase from 
baseline 
Leukocytes 
×103/µL 
≤ 2.8 
≥ 16.0 
Lymphocytes 
×103/µL 
<0.5  
>20 
Neutrophils 
×103/µL 
<1.0 
 
Platelets 
×103/µL 
<75 
≥700 
ALT = alanine aminotransferase; AST = aspartate aminotransferase;  
GGT = gamma-glutamyltransferase; PCS = potentially clinically significant; 
LLN=Lower limit of normal; ULN=Upper limit of normal  
 
12.5.2. 
Potentially Clinically Significant Abnormal Liver Function Tests  
Patients meeting criteria for abnormal liver function tests (LFTs) by time point will be 
listed.  Threshold values of interest for LFTs are provided in Table 4. 
Table 4: Liver Function Tests Criteria  
Parameter 
Criterion 
ALT 
>3×ULN; >5×ULN; >10×ULN 
AST 
>3×ULN; >5×ULN; >10×ULN 
ALT and TBL 
ALT 3×ULN and TBL >2×ULN 
AST and TBL 
AST 3×ULN and TBL >2×ULN 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total 
bilirubin; ULN = upper limit of normal 
 


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For a combined criterion to be fulfilled, all conditions have to be fulfilled by the same 
laboratory measurement. Only patients with newly occurring values (at least one 
post-baseline measurement and meeting the criterion but not meeting the criterion at 
baseline) will be counted. 
12.6. 
Vital Signs 
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiration 
rate and temperature will be measured at Screening and subsequent visits following the 
SoA table (protocol Section 1.3). 
The summary of observed values of the vital sign parameters will be presented at 
baseline, each planned visit, and worst-case post-baseline (includes both scheduled and 
unscheduled assessments) as time points.  Worst-case values will be presented based on 
worst minimum and worst maximum values. 
A listing of all vital sign assessments along with the change from baseline values, will 
be produced. 
12.6.1. 
Potentially Clinically Significant (PCS) Vital Sign Abnormalities 
PCS criteria will be used to assess PCS vital sign abnormalities.  The incidence of patients 
meeting PCS criteria for pulse rate, SBP, and DBP at baseline, planned visit, and worst-
case post-baseline (includes both scheduled and unscheduled assessments) will be 
provided. For computing percentages, the denominator will be the number of patients 
with a post-baseline value for the specific vital sign parameter and the respective time 
point. A listing of patients with PCS vital signs results will also be generated. 
The PCS criteria are shown in Table 5. 
Table 5: Vital Signs PCS Criteria  
Parameter 
PCS Criterion 
Pulse rate 
≤50 bpm 
≤50 bpm and decrease of ≥15 bpm from Baseline 
≥120 bpm 
≥120 bpm and increase of ≥15 bpm from Baseline  
Systolic blood pressure 
≤90 mmHg 
≤90 mmHg and decrease of ≥20 mmHg from Baseline 
≥180 mmHg 
≥180 mmHg and increase of ≥20 mmHg from Baseline 
Diastolic blood pressure 
≤50 mmHg 
≤50 mmHg and decrease of ≥15 mmHg from Baseline 
≥105 mmHg 
≥105 mmHg and increase of ≥15 mmHg from Baseline  
 


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12.7. 
General Physical Examination 
General physical examination will be performed at the Screening Visit by a physician at 
the investigative site. Additional full physical examinations may be performed during the 
study if clinically indicated. 
 
Abnormal results (clinically significant or not clinically significant) will be listed by body 
system.  
12.8. 
Urology-Oriented Examination 
Urology-oriented examinations as described in the Sec 8.3.1 of the protocol, will be 
performed at screening and subsequent visits following the protocol SoA table (Section 
1.3). 
A urological examination will be performed at the Screening Visit, Treatment Visit 1, 
and at the 3-month Visit (or ET) by a physician at the investigative site. Additional 
urological examinations may be performed during the study if clinically indicated. 
A listing of patients with abnormal urology examination findings either clinically 
significant or not clinically significant will be provided.  
13. 
PHARMACOKINETIC ANALYSES 
Not applicable. 
14. 
PHARMACODYNAMIC AND BIOMARKER ANALYS 
Not applicable. 
15. 
PHARMACOKINETIC/PHARMACODYNAMIC 
ANALYSES 
Not applicable. 
16. 
PHARMACOGENETIC DATA ANALYSES 
 Not applicable. 
 
17. 
REFERENCES 
Brookmeyer R., Crowley J. A Confidence Interval for the Median Survival Time. 
Biometrics.Vol. 38, 1982:29-41.  
 
18. 
APPENDICES 
 


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Appendix A Patient Questionnaire 
The purpose of this questionnaire is for you to share your experience on how you felt 
receiving UGN-102 intravesical instillation at home. Please indicate the extent to which 
you felt comfortable and safe with the treatment at home and fill in the questionnaire as 
per your experience.  
Part 1  Must be completed at each home instillation visit after the instillation is 
completed  
 
  
  
Not at all  
A little  
Quite 
a bit  
Very 
much  
  
Comfort  
  
  
  
  
1.  
Were you more comfortable with 
today’s instillation at home than at 
your doctor’s office?  
  
  
  
  
2.  
  
Did you find it more difficult receiving 
today’s instillation at home than at 
your doctor’s office?  
  
  
  
  
Please explain (free text):  
 
 
 
 
3.  
Did the courtesy and caregiving of the 
home health professional make you 
feel comfortable?  
  
  
  
  
  
Safety  
  
  
  
  
4.  
  
Did you have any concerns receiving 
the instillation at home, away from the 
doctor’s office?  
  
  
  
  
Please explain (free text):  
 
 
 
 
  
Communication  
  
  
  
  
5.  
Did you receive clear and sufficient 
instructions on what to do and what to 
expect before the instillation?  
  
  
  
  
6.  
Did you receive clear and sufficient 
instructions on what to do and what to 
expect after the instillation?  
  
  
  
  
  
Preference  
  
  
  
  


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7.  
  
Did you prefer to have today’s 
instillation done at home compared to 
the doctor’s office?  
  
  
  
  
Please explain (free text):  
 
 
 
 
  
Overall experience  
  
  
  
  
8.  
  
Overall are you satisfied with today’s 
instillation performed at home?  
  
  
  
  
Please explain (free text):  
 
 
 
 
Part 2  Must be completed at the 3-month Visit (End of Study) or Early Termination Visit  
 
The purpose of this questionnaire is for you to share your recommendation based on 
your experience on this study.  
1. Will you recommend home instillations of UGN-102 for other patients with 
non-muscle invasive bladder cancer (NMIBC)?  
• 
Yes  
• 
No  
Please explain (free text):  
2. Will you recommend home instillations of UGN-102 instead of having 
transurethral resection of bladder tumors (TURBT) for other patients with 
NMIBC?  
• 
Yes  
• 
No  
• 
Not applicable  
Please explain (free text):  
 


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Appendix B Home Health Professional Questionnaire 
The purpose of this questionnaire is for you to share your experience on how you 
felt administering UGN-102 intravesical instillation at the patient’s home. Please 
indicate the extent to which you felt comfortable and safe with the treatment at the 
patient’s home and fill in the questionnaire as per your experience.  
Part 1  Must be completed at each home instillation visit after the instillation is 
completed  
1. Were you comfortable performing the instillation at this patient’s home?  
• 
Yes  
• 
No  
Please explain (free text):  
2. Was it difficult to perform the instillation at this patient’s home?  
• 
Yes  
• 
No  
Please explain (free text):  
3. Did you have any concerns performing the instillation in the home setting?  
• 
Yes  
• 
No  
Please explain (free text):  
4. Did you have sufficient support performing the instillation in the home 
setting?  
• 
Yes  
• 
No  
Please explain (free text):  
Part 2  Must be completed starting at the second home instillation visit (Treatment Visit 
3 onwards)  
1. Did you perform the previous home instillation for this patient?  
• 
Yes  
• 
No  
 
 
 


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Appendix C Investigator Questionnaire 
Must be completed at the 3-month Visit (End of Study) or Early Termination Visit  
 
The purpose of this questionnaire is to understand how comfortable and safe patients 
and home health professionals considered home instillation of UGN-102. Please answer 
the questions below.  
1. Was the experience of having your patient receive instillations at home 
more difficult, less difficult, or not different than having them receive 
instillation in your office?  
• 
More difficult  
• 
Less difficult  
• 
Not different  
Please explain (free text):  
2. How can we improve the overall experience (free text)? 
 
 
Appendix D Imputation Rules for Missing or Partial Dates 
The partial date imputation will follow Analysis Data Model (ADaM) conventions. The 
ADaM approach is to populate the numeric date variables with the imputed date and add 
a flag variable to the dataset that indicates the level of imputation. The flag variable can 
contain the values: blank, 'D,' 'M,' 'Y.' 
blank: indicates that no imputation was done 
D='Day': indicates that the day portion of the date is imputed 
M='Month': indicates that the month and day portions of the date are imputed 
Y='Year': indicates that the entire date (year, month, and day) is imputed. 
 
Details on imputing partial dates for specific datasets are outlined below.  
 
Table 6: Imputation Rules of Adverse Event (AE) Start and End Dates 
 
Dataset Date Missing 
Element 
Rule 
AE 
Start 
Date 
day, 
month, 
and year 
• No Imputation for completely missing dates 
 
 
year 
• No Imputation if year is missing 
 
 
day, 
month 
• If year of AE start date = year of study treatment 
start date, then set AE start date = Study treatment 
start date 


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• Else set AE start date = 01JANYYYY 
• If AE end date is not missing and imputed AE start 
date > AE end date, then imputed AE start date 
should be set to AE end date. 
 
 
day 
• If month and year of start date = month and year of 
treatment start date, then set AE start date = study 
treatment start date. 
• Else set start date = 01MONYYYY. 
• If AE end date is not missing and imputed AE start 
date > AE end date, then imputed AE start date 
should be set to AE end date. 
 
End 
Date 
 
• No imputation for partial end dates will be 
performed 
 
Table 7: Imputation Rules of Prior or Concomitant Medication (CM) Start and End 
Dates 
 
Dataset Date 
Missing 
Element 
Rule 
CM 
Start 
Date 
day, 
month, 
and year 
• No Imputation for completely missing dates 
 
 
year 
• No Imputation if year is missing 
 
 
day, 
month 
• If year of CM start date = year of study treatment 
start date, then set CM start date = Study treatment 
start date 
• Else set CM start date = 01JANYYYY 
• If imputed CM start date > CM end date (complete 
or imputed), then imputed CM start date should be 
set to CM end date. 
 
 
day 
• If month and year of start date = month and year of 
treatment start date, then set CM start date = study 
treatment start date. 
• Else set start date = 01MONYYYY. 
• If imputed CM start date > CM end date (complete 
or imputed), then imputed CM start date should be 
set to CM end date. 
 
End 
Date 
year 
• No imputation for partial end dates will be 
performed 
 
 
day, 
month 
• Min (Last visit date, 31DECYYYY, Date of Death) 
• If imputed CM start date > CM end date (complete 
or imputed), then imputed CM start date should be 
set to CM end date. 


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day 
• Min (Last visit date, last day of the month, death 
day) 
• If imputed CM start date > CM end date (complete 
or imputed), then imputed CM start date should be 
set to CM end date. 
 
 
Table 8: Imputation Rules of Urothelial Carcinoma (UC) Related Medical History 
(MH) Start and End Dates 
 
Dataset Date Missing 
Element 
Rule 
(Only impute missing dates for MH related to UC) 
MH 
Start 
Date 
day, 
month, 
and year 
• No Imputation for completely missing dates 
 
 
year 
• No Imputation if year is missing 
 
 
day, 
month 
• If year of MH start date = year of start date of the 
current urothelial carcinoma diagnosis, then set MH 
start date = min (01JANYYYY, Start date of the 
current urothelial carcinoma diagnosis -1). 
• Else if the year of MH start date < year ofstart date of 
the current urothelial carcinoma diagnosis, then set 
MH start date = 01JANYYYY. 
• If imputed MH start date > MH end date (complete or 
imputed), then imputed MH start date should be set to 
MH end date. 
 
 
day 
• If month and year of start date = month and year 
ofstart date of the current urothelial carcinoma 
diagnosis, then set MH start date = Start date of the 
current urothelial carcinoma diagnosis -1. 
• Else set start date = 01MONYYYY. 
• If imputed MH start date > MH end date (complete or 
imputed), then imputed MH start date should be set to 
MH end date. 
 
End 
Date 
year 
• No imputation for partial end dates will be performed 
 
 
day, 
month 
• Min (Start date of the current urothelial carcinoma 
diagnosis, Last visit date, 31DECYYYY, Date of 
Death) 
• If imputed MH start date > MH end date (complete or 
imputed), then imputed MH start date should be set to 
MH end date. 
 
 
day 
• Min (Start date of the current urothelial carcinoma 
diagnosis, Last visit date, last day of the month, death 
day) 


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• If imputed MH start date > MH end date (complete or 
imputed), then imputed MH start date should be set to 
MH end date. 
 
 
Table 9: Imputation Rules of Prior or Concomitant Surgical Procedures (PR) Start 
Date 
 
Dataset Date Missing 
Element 
Rule 
PR 
Start 
Date 
day, 
month, 
and year 
• No Imputation for completely missing dates 
 
 
year 
• No Imputation if year is missing 
 
 
day, 
month 
• If the surgical procedure was performed for a prior 
history of UC or MH, then do: 
o If the year of PR start date = year of inform 
consent date, then set PR start date = min 
(01JANYYYY, Inform consent date -1). 
o Else if the year of PR start date < year of 
inform consent date, then set PR start date = 
01JANYYYY. 
• If the surgical procedure was NOT performed for a 
prior history of UC or MH, then do: 
o If year of PR start date = year of study 
treatment start date, then set PR start date = 
Study treatment start date -1. 
o Else set CM start date = 01JANYYYY 
 
 
day 
• If month and year of PR start date = month and year 
of treatment start date, then set PR start date = study 
treatment start date -1. 
• Else set start date = 01MONYYYY. 
 
 
 


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Appendix E Laboratory CTCAE Grade Version 5.0 Criteria  
 
Table 10: Laboratory CTCAE Grade Version 5.0 Criteria 
 
 
Lab Parameter 
Conventional 
Unit 
CTCAE Grade v5.0 
Grade 
0 
Grade 1 
Grade 2 
Grade 
3 
Grade 4 
Hemoglobin 
decreased 
(Anemia) 
g/dL 
≥LLN 
10 – 
<LLN 
8 – <10 
< 8 
 
Hemoglobin 
increased  
g/dL 
≤ULN >ULN – 
2 + ULN 
>2 + ULN – 
4 + ULN 
>4 + 
ULN 
 
Hypoglycemia 
(Glucose 
decreased) 
mg/dL 
≥LLN 
55 – 
<LLN  
40 – <55  
30 – 
<40  
<30  
Glucose 
(hyperglycemia) 
mg/dL 
LLN – 
ULN 
>ULN – 
160 
>160 – 250 
>250 
–500 
>500 
Albumin 
g/dL 
≥LLN 
<LLN – 3 <3 – 2 
<2 
Life-
threatening 
consequences; 
urgent 
intervention 
indicated 
Alkaline 
phosphatase 
 
≤ULN 
>ULN – 
2.5 × 
ULN 
>2.5 – 5.0 × 
ULN 
>5.0 – 
20.0 × 
ULN 
>20.0 × ULN 
Alanine 
aminotransferase 
increased 
U/L 
≤ULN >ULN – 
3 × ULN 
>3 × ULN – 
 5 × ULN 
>5 × 
ULN 
– 20 × 
ULN 
> 20 × ULN 
Aspartate 
aminotransferase 
increased 
U/L 
≤ULN >ULN – 
3 × ULN 
>3 × ULN – 
 5 × ULN 
>5 × 
ULN 
– 20 × 
ULN 
> 20 × ULN 
Blood bilirubin 
increased 
mg/dL 
≤ULN >ULN – 
1.5 × 
ULN 
>1.5 × ULN 
– 3 × ULN 
>3 × 
ULN 
– 10 × 
ULN 
>10 × ULN 
Creatinine 
increased 
mg/dL 
≤ULN >ULN – 
1.5 × 
ULN 
>1.5 × ULN 
– 3 × ULN 
>3 × 
ULN 
– 6 × 
ULN 
>6 × ULN 
Calcium 
(hypocalcemia)
mg/dL 
LLN – 
ULN
<LLN – 
8.0
<8.0 – 7.0 
<7.0 – 
6.0
<6.0 


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Calcium 
(hypercalcemia)
mg/dL 
LLN – 
ULN
>ULN – 
11.5
>11.5 – 12.5 
>12.5 
– 13.5
>13.5 
Gamma-
glutamyl 
transferase 
increased 
U/L 
≤ULN >ULN – 
2.5 × 
ULN 
>2.5 × ULN 
– 5 × ULN 
>5 × 
ULN 
– 20 × 
ULN 
> 20 × ULN 
Eosinophils 
increased 
×103/µL 
≤ULN >ULN 
and 
>Baseline 
 
 
 
Lymphocyte 
count decreased 
×103/µL 
≥LLN 
0.8 – < 
LLN 
0.5 – <0.8 
0.2 – 
<0.5 
<0.2 
Lymphocyte 
count increased 
×103/µL 
≤4  
 
 
>4 - 20 
>20 
 
Neutrophil count 
decreased 
×103/µL 
≥LLN 
1.5 – 
<LLN 
1.0 – <1.5 
0.5 – 
<1.0 
<0.5 
Platelet count 
decreased 
×103/µL 
≥LLN 
75 – 
<LLN 
50 – <75 
25 – 
<50 
<25 
White blood cell 
decreased 
×103/µL 
≥LLN 
3.0 – 
<LLN 
2.0 – <3.0 
1.0 – 
<2.0 
<1.0 
White blood cell 
increased 
(eukocytosis) 
×103/µL 
≤100  
 
 
 
>100 
 
Hyperkalemia 
(Potassium 
increased) 
mEq/L 
≤ULN >ULN – 
5.5  
>5.5 – 6.0  
>6.0 – 
7.0  
>7.0  
Hypokalemia 
(Potassium 
decreased) 
mEq/L 
≥LLN 
3.0 – 
<LLN  
Symptomatic 
with 3.0 – 
 <LLN  
2.5 – 
<3.0  
<2.5  
Hypernatremia 
(Sodium 
increased) 
mEq/L 
≤ULN >ULN – 
150  
>150 – 155  
>155 
– 160  
>160  
Hyponatremia 
(Sodium 
decreased) 
mEq/L 
≥LLN 
130 – 
<LLN  
125 – <130  
120 – 
<125  
<120  
Notes: ULN = upper limit of normal; LLN = lower limit of normal 
 
 
Appendix F Data Display Specifications   
The data display specifications are contained in a separate document. The display mock-
shells are provided as a guideline - the format and layout may be revised due to potential 
limitations of the programs and tools used to produce the displays. 
The following data displays will be provided for the End of Study analysis. 
 
Table 11: Table of Contents for Data Display Specifications 
 


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Type 
Section 
Number 
Title 
Table 
Patient 
Info 
14.1.1 
Summary of Analysis Sets 
Table 
Patient 
Info 
14.1.2 
Summary of Patient Disposition 
Table 
Patient 
Info 
14.1.3 
Summary of Demographics and Baseline Characteristics 
Table 
Patient 
Info 
14.1.4 
Summary of Prior and Concurrent Urothelial Carcinoma 
Medical Condition 
Table 
Patient 
Info 
14.1.5 
Summary of Concomitant Medications 
Table 
Patient 
Info 
14.1.6 
Summary of Concomitant Surgical Procedures 
Table 
Efficacy 
14.2.1 
Summary of Response Rate at the 3-Month Disease 
Assessment 
Table 
Feedback 
Question
naire 
14.2.2.1 
Summary of Feedback Questionnaire Observed Scores by 
Table 
Feedback 
Question
naire  
14.2.2.2 
Summary of Feedback Questionnaire by Home Healthcare 
Professional (HHP) 
Table 
Feedback 
Question
naire  
14.2.2.3 
Summary of End of Study Feedback Questionnaire by Patient 
and Investigator 
Table 
Safety 
14.3.1.1 
Overall Summary of Adverse Events 
Table 
Safety 
14.3.1.2 
Incidence of Treatment-Emergent Adverse Events by System 
Organ Class, Preferred Term and Worst Severity 
Table 
Safety 
14.3.1.3 
Incidence of Treatment-Emergent Adverse Events by 
Preferred Term and Worst Severity 
Table 
Safety 
14.3.1.4 
Incidence of Treatment Related Treatment-Emergent Adverse 
Events by Preferred Term 
Table 
Safety 
14.3.1.5 
Incidence of Procedure Related Treatment-Emergent Adverse 
Events by Preferred Term 
Table 
Safety 
14.3.1.6 
Incidence of Treatment Related Treatment-Emergent Adverse 
Events by System Organ Class and Preferred Term 
Table 
Safety 
14.3.2.1 
Incidence of Treatment-Emergent Adverse Events of Special 
Interest by Category and Preferred Term 
Table 
Safety 
14.3.2.2 
Summary of Characteristics of Treatment-Emergent Adverse 
Event of Special Interest by Category 
Table 
Safety 
14.3.4 
Summary of Potentially Clinically Significant Laboratory 
Values by Time Point 
Table 
Safety 
14.3.5 
Summary of Potentially Clinically Significant Vital Signs by 
Time Point 
Table 
Safety 
14.3.6.1 
Summary of Treatment Exposure of UGN-102 
Table 
Safety 
14.3.6.2 
UGN-102 Volume (mL) and Mitomycin Dose (mg) by Visit 
Listing 
Patient 
Info 
16.2.1 
Patient Disposition 


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Listing 
Patient 
Info 
16.2.2.1 
Protocol Deviation 
Listing 
Patient 
Info 
16.2.2.2 
Patients with Inclusion/Exclusion Criteria Deviations 
Listing 
Patient 
Info 
16.2.4.1 
Demographic and Baseline Characteristics 
Listing 
Patient 
Info 
16.2.4.2 
Medical History 
Listing 
Patient 
Info 
16.2.4.3 
Prior and Concurrent Urothelial Carcinoma Medical 
Condition 
Listing 
Patient 
Info 
16.2.4.4 
Prior and Concomitant Medications 
Listing 
Patient 
Info 
16.2.4.5 
Prior and Concomitant Surgical Procedures 
Listing 
Patient 
Info 
16.2.4.6 
Prior NMIBC Diagnosis and TURBT History 
Listing 
Safety 
16.2.5 
UGN-102 Administration 
Listing 
Efficacy 
16.2.6.1 
Visit Level Disease Assessment Based on Cystoscopy, 
Histopathology, and Cytology 
Listing 
Feedback 
Question
naire 
16.2.6.2 
Feedback Questionnaire – Patient Questionnaire 
Listing 
Feedback 
Question
naire 
16.2.6.3 
Feedback Questionnaire – Home Health Professional 
Questionnaire 
Listing 
Feedback 
Question
naire 
16.2.6.4 
Feedback Questionnaire – Investigator Questionnaire 
Listing 
Safety 
16.2.7.1 
All Adverse Events 
Listing 
Safety 
16.2.7.2 
Serious Adverse Events 
Listing 
Safety 
16.2.7.3 
Deaths 
Listing 
Safety 
16.2.8.1 
Hematology Laboratory Values Lying Outside the Laboratory 
Reference Ranges 
Listing 
Safety 
16.2.8.2 
Chemistry Laboratory Values Lying Outside the Laboratory 
Reference Ranges 
Listing 
Safety 
16.2.8.3 
Urinalysis Laboratory Values 
Listing 
Safety 
16.2.8.4 
Potentially Clinically Significant (PCS) Laboratory Values 
and Abnormal LFT 
Listing 
Safety 
16.2.8.5 
Urine Culture 
Listing 
Safety 
16.2.9.1 
Vital Signs Results 
Listing 
Safety 
16.2.9.2 
Potentially Clinically Significant (PCS) Vital Sign Results 
Listing 
Safety 
16.2.10.1 
General Physical Examinations with Abnormal Results 
Listing 
Safety 
16.2.10.2 
Urology-Oriented Physical Examinations with Abnormal 
Results