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 Transurethral resection of bladder tumors TURBT
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 282
Healthy volunteers: no

Brief summary:
This global, randomized, controlled, open-label Phase 3 study was designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Detailed description:
Eligible patients were randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization was stratified by the presence of a previous LG-NMIBC episode within 1 year of the current diagnosis (yes or no). Starting on Day 1, patients randomized to the UGN-102 ± TURBT arm will receive 6 weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone arm underwent TURBT.

All patients returned to the clinic approximately 3 months after the start of treatment for a disease assessment visit. Response to treatment was determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions, and voiding urine cytology. Patients confirmed to have a complete response (CR), defined as having no detectable disease (NDD) in the bladder, received no further treatment and entered the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) due to residual LG disease in either treatment arm underwent TURBT of any remaining lesions and then entered the Follow-up Period of the study.

During the Follow-up Period, patients returned to the clinic every 3 months to determine if they remained disease free. Patients remained on study until completion of all follow-up visits or until disease recurrence, disease progression, or death was documented, whichever occurred first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit were considered to have completed the study and released to the care of their treating physician.

Study enrollment was stopped early by the sponsor to pursue an alternative development strategy for UGN-102 in the treatment of bladder cancer. Patients who had consented at the time the trial terminated were permitted to continue, but follow-up was terminated once the last patient had been followed for 15 months after the start of treatment.

Arms:
arm 1: 6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102). arm 2: TURBT on Day 1 + repeat TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the initial TURBT).

Interventions: intervention 1: UGN-102 intervention 2: TURBT
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. intervention 2: The current standard of care for treatment of LG-IR-NMIBC is TURBT under general anesthesia.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL 
Protocol BL006 version 2.0 
 
1 
Title Page 
Protocol Title: A Randomized, Controlled, Open-label Study of the Efficacy, Durability, 
and Safety of UGN-102 With or Without TURBT in Patients with 
Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer 
(LG IR-NMIBC) (ATLAS) 
 
Protocol Number: BL006 
Compound: UGN-102 (mitomycin) for intravesical solution  
Brief Title: A Phase 3 Study of UGN-102 for Low-Grade Intermediate-Risk Non-Muscle 
Invasive Bladder Cancer (ATLAS) 
Study Phase: 3 
Sponsor Name: UroGen Pharma Ltd.  
Legal Registered Address:  
9 Ha’Ta’asiya Street  
Ra’anana, Israel 4365405 
 
Regulatory Agency Identifier Number(s): 
IND: 138749 
EudraCT: 2020-003541-11 
Protocol Status 
Version 
Date 
Original 
1.0 
03 Aug 2020 
Administrative Revision 1 
1.1 
16 Sep 2020 
Amendment 1 
2.0 
20 Dec 2021 
 
 
 
Property of UroGen Pharma, Ltd 
Confidential 
May not be used, divulged, published or otherwise disclosed without written consent of 
UroGen Pharma, Ltd. 


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Protocol BL006 version 2.0 
 
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Key Roles and Contact Information 
 
Medical Director /Medical Monitor  
, MD, UroGen Pharma 
 
 
 
Study Director  
, UroGen Pharma 
 
 
 
Quality Assurance 
, UroGen Pharma 
 
 
qa@urogen.com 
 
Study Logistics 
, UroGen Pharma 
 
 


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Protocol BL006 version 2.0 
 
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Table of Contents 
Key Roles and Contact Information ............................................................................................2 
List of In-text Tables ........................................................................................................................6 
List of In-text Figures ......................................................................................................................6 
Statement of Compliance ..............................................................................................................7 
Notification of Early Study Enrollment Closure (10 Nov 2021) ................................................8 
1. 
Protocol Summary ..........................................................................................................9 
1.1. 
Synopsis ............................................................................................................................9 
1.2. 
Schema ............................................................................................................................13 
1.3. 
Schedule of Activities (SoA) – Phase 3 Bladder UGN-102 Patient ...............................14 
1.4. 
Schedule of Activities (SoA) – Phase 3 Bladder TURBT Patient ..................................17 
Abbreviations ...............................................................................................................................20 
2. 
Introduction ...................................................................................................................23 
2.1. 
Study Rationale ...............................................................................................................24 
2.2. 
Benefit/Risk Assessment ................................................................................................25 
2.2.1. 
Risk Assessment .............................................................................................................25 
2.2.2. 
Benefit Assessment .........................................................................................................26 
2.2.3. 
Overall Benefit: Risk Conclusion ...................................................................................26 
3. 
Objectives and Endpoints ............................................................................................27 
4. 
Study Design ..................................................................................................................29 
4.1. 
Overall Design ................................................................................................................29 
4.2. 
Scientific Rationale for Study Design ............................................................................30 
4.2.1. 
Patient Input into Design ................................................................................................30 
4.3. 
Justification for Dose ......................................................................................................30 
4.4. 
End-of-Study Definition .................................................................................................31 
4.5. 
Patient Completion and Withdrawal ...............................................................................31 
5. 
Study Population ...........................................................................................................32 
5.1. 
Inclusion Criteria ............................................................................................................32 
5.2. 
Exclusion Criteria ...........................................................................................................33 
5.3. 
Lifestyle Considerations .................................................................................................34 
5.4. 
Screen Failures ................................................................................................................34 
5.5. 
Strategies for Recruitment and Retention .......................................................................34 
5.6. 
Criteria for Temporarily Delaying Administration of Study 
Intervention Administration ............................................................................................35 
6. 
Study Intervention(s) and Concomitant Therapy ......................................................36 
6.1. 
Study Intervention(s) Administered ................................................................................36 
6.1.1. 
Study Treatment Description ..........................................................................................36 
6.1.2. 
Admixture and Administration Ancillary Supplies ........................................................37 
6.1.3. 
Dosing and Administration .............................................................................................37 
6.1.4. 
Preparation and Administration Supplies .......................................................................38 
6.2. 
Admixture/Handling/Storage/Accountability .................................................................39 
6.2.1. 
Acquisition and Accountability ......................................................................................39 


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6.2.2. 
Formulation, Appearance, Packaging, and Labeling ......................................................40 
6.2.3. 
Product Storage and Stability..........................................................................................40 
6.2.4. 
Admixture .......................................................................................................................40 
6.2.5. 
Product Quality Complaint Handling .............................................................................40 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................41 
6.4. 
Study Intervention Compliance ......................................................................................41 
6.5. 
Dose Modification ..........................................................................................................42 
6.5.1. 
Retreatment Criteria ........................................................................................................42 
6.6. 
Continued Access to Study Intervention after the End of the Study ..............................42 
6.7. 
Treatment of Overdose ...................................................................................................42 
6.8. 
Past/Concomitant and Prohibited Therapy .....................................................................42 
6.8.1. 
Rescue Medicine .............................................................................................................42 
7. 
Discontinuation of Study Treatment and Patient 
Discontinuation/Withdrawal........................................................................................43 
7.1. 
Discontinuation of Study Treatment ...............................................................................43 
7.1.1. 
Temporary Withholding of Study Treatment .................................................................43 
7.1.2. 
Rechallenge .....................................................................................................................43 
7.2. 
Patient Discontinuation/Withdrawal from the Study ......................................................44 
7.3. 
Lost to Follow-up............................................................................................................44 
8. 
Study Assessments and Procedures.............................................................................45 
8.1. 
Study Assessments and Procedures by Visit ..................................................................45 
8.1.1. 
Screening And Randomization Period (Day -28 to Day 0 or Day -14 to Day 0) ...........45 
8.1.2. 
Treatment Period: Visits 2a to 2f (Day 1 to 36 / Week 1 to 6) for UGN-102 ± 
TURBT Patients or Visit 2 (Day 1 / Week 1) for TURBT Alone Patients.....................46 
8.1.3. 
Waiting Period: Week 7 to 13 (UGN-102 ± TURBT) or Week 2 to 13 
(TURBT Alone) ..............................................................................................................47 
8.1.4. 
Monthly Telephone Contact Visits: Months 2, 4, and 5 ± 1 week (UGN-102 ± 
TURBT) or Months 1, 2, 4, and 5 ± 1 week (TURBT Alone) .......................................47 
8.1.5. 
Disease Assessment Visit: Visit 3 (Month 3 ± 1 week) .................................................47 
8.1.6. 
Follow-up Period including EOS Visit: Visit 4, 5, 6, 7, 8, 9, 10 
(Months 6, 9, 12, 15, 18, 21, 24 (EOS) ± 2 weeks) ........................................................48 
8.1.7. 
Unscheduled Visits .........................................................................................................49 
8.2. 
Efficacy Assessments .....................................................................................................49 
8.2.1. 
Measurements for Evaluation of Response at 3-Month Visit and 
Follow-up Visits..............................................................................................................49 
8.2.2. 
Evaluation of Response at 3-Month Visit and Follow-up Visits 
(Disease Assessment)......................................................................................................50 
8.2.3. 
Assessment of Tumor Progression..................................................................................51 
8.2.4. 
Assessment of Tumor Recurrence ..................................................................................51 
8.2.5. 
Pathological Evaluation ..................................................................................................51 
8.3. 
Safety Assessments .........................................................................................................52 
8.3.1. 
Physical Examinations ....................................................................................................52 
8.3.2. 
Vital Signs .......................................................................................................................52 
8.3.3. 
Clinical Safety Laboratory Assessments ........................................................................52 
8.3.4. 
Urinalysis ........................................................................................................................54 


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8.3.5. 
Pregnancy Testing ...........................................................................................................54 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and 
Other Safety Reporting ...................................................................................................54 
8.4.1. 
Safety and Other Assessments ........................................................................................55 
8.4.2. 
Adverse Events and Serious Adverse Events .................................................................55 
8.4.3. 
Time Period and Frequency for Collecting AE and SAE Information ...........................58 
8.4.4. 
Method of Detecting AEs and SAEs ..............................................................................59 
8.4.5. 
Follow-up of AEs and SAEs ...........................................................................................59 
8.4.6. 
Regulatory Reporting Requirements for SAEs ...............................................................59 
8.4.7. 
Serious Adverse Event Reporting ...................................................................................60 
8.4.8. 
Pregnancy ........................................................................................................................61 
8.4.9. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................................62 
8.4.10. Adverse Events of Special Interest .................................................................................62 
8.5. 
Pharmacokinetics ............................................................................................................62 
8.6. 
Genetics and/or Pharmacogenomics ...............................................................................62 
8.7. 
Biomarkers ......................................................................................................................62 
8.8. 
Immunogenicity Assessments.........................................................................................62 
8.9. 
Health Economics/Medical Resource Utilization and Health Economics ......................62 
9. 
Statistical Considerations .............................................................................................63 
9.1. 
Statistical Hypotheses .....................................................................................................63 
9.2. 
Sample Size Determination ............................................................................................63 
9.3. 
Analysis Sets ...................................................................................................................63 
9.4. 
Statistical Analyses .........................................................................................................64 
9.4.1. 
General Considerations ...................................................................................................64 
9.4.2. 
Primary Endpoint(s) ........................................................................................................64 
9.4.3. 
Secondary Endpoint(s) ....................................................................................................65 
9.4.4. 
Exploratory Endpoints ....................................................................................................66 
9.4.5. 
Safety Analysis ...............................................................................................................67 
9.4.6. 
Other Analysis ................................................................................................................68 
9.5. 
Interim Analysis ..............................................................................................................68 
10. 
Supporting Documentation and Operational Considerations ..................................69 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations .............................................69 
10.1.1. Regulatory and Ethical Considerations ...........................................................................69 
10.1.2. Finance and Insurance .....................................................................................................69 
10.1.3. 
Consent and Other Informational Documents Provided to Patients ...............................70 
10.1.4. Data Protection, Confidentiality, and Privacy ................................................................70 
10.1.5. Data Review Committee .................................................................................................71 
10.1.6. Dissemination of Clinical Study Data .............................................................................71 
10.1.7. Safety Oversight..............................................................................................................71 
10.1.8. Clinical Monitoring .........................................................................................................71 
10.1.9. Data Quality Assurance ..................................................................................................72 
10.1.10. Data Handling and Record Keeping ...............................................................................73 
10.1.11. Protocol Deviations .........................................................................................................74 
10.1.12. Source Documents ..........................................................................................................74 


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10.1.13. Study and Site Start and Closure ....................................................................................74 
10.1.14. Publication Policy ...........................................................................................................75 
10.1.15. Conflict of Interest Policy ...............................................................................................76 
11. 
References ......................................................................................................................77 
 
List of In-text Tables 
Table 1: UGN-102 Components .................................................................................................. 36 
Table 2: Vial Composition of Mitomycin for Solution................................................................ 37 
Table 3: Physical Examinations ................................................................................................... 52 
Table 4: Laboratory Safety Assessments* ................................................................................... 53 
Table 5: Evaluation Based on Cystoscopy and Biopsy/Histopathology ...................................... 79 
Table 6: Evaluation Based on Urine Cytology, Diagnosis of UTUC and 
Random Bladder Biopsies ............................................................................................. 81 
Table 7: Evaluation of Response Based on All Assessments ...................................................... 83 
 
List of In-text Figures 
Figure 1. Structure of Mitomycin, USP ........................................................................................ 36 
Figure 2. Evaluation Based on Cystoscopy and Biopsy/Histopathology ...................................... 80 
Figure 3. Evaluation Based on Urine Cytology, Diagnosis of UTUC and 
Random Bladder Biopsy ................................................................................................ 82 
 


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Protocol BL006 version 2.0 
 
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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 BL006 version 2.0 
 
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Notification of Early Study Enrollment Closure (10 Nov 2021) 
UroGen Pharma Ltd. (Sponsor) closed enrollment in Study BL006 on 10 Nov 2021 in order to 
pursue an alternative development strategy for UGN-102 in patients with low grade intermediate 
risk non-muscle invasive bladder cancer (LG IR NMIBC). This decision was not based on new 
information about the efficacy or safety of UGN-102, and UGN-102 continues to have a favorable 
benefit-risk profile that supports its continued development for treatment of LG IR NMIBC. 
Patients who provided written informed consent to participate in Study BL006 on or before 
10 Nov 2021 are permitted to continue their study participation according to the study protocol. 


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Protocol BL006 version 2.0 
 
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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Randomized, Controlled, Open-label Study of the Efficacy, Durability, 
and Safety of UGN-102 With or Without TURBT in Patients with Low 
Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG IR-
NMIBC) (ATLAS) 
Brief Title: A Phase 3 Study of UGN-102 for Low-Grade Intermediate-Risk Non-Muscle 
Invasive Bladder Cancer (ATLAS) 
Overall Design: This study is a global, randomized, controlled, open-label Phase 3 study 
designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical 
solution (i.e., intravesical instillation) with or without Transurethral Resection of Bladder 
Tumors (TURBT) vs. TURBT alone in the treatment of patients with LG IR-NMIBC. 
Eligible patients who have signed the informed consent and met all study entry criteria will be 
randomized in a 1:1 ratio to UGN-102 with or without TURBT or TURBT alone. Patients 
randomized to the UGN-102 group will receive 6 weekly intravesical instillations of UGN-102 
followed by TURBT only if needed and patients randomized to the TURBT alone group will 
undergo TURBT followed by repeat TURBT if needed.  
All patients will return to the clinic at approximately 3 months from the initiation of treatment 
for determination of response to treatment. Following this initial evaluation, all patients 
confirmed to have had a complete response (CR) will receive no further treatment and will enter 
the follow-up period of the study. Patients confirmed to have had a non-complete 
response (NCR) in either treatment arm will undergo TURBT of any remaining lesions and will 
then also enter the follow-up period of the study. Note: If the Investigator determines that a 
formal TURBT in the operating room is unnecessary following cystoscopy and biopsy of 
remaining lesions (e.g., residual disease can be addressed by in office biopsy and/or fulguration), 
such an alternative procedure is permitted based on the Investigator’s medical judgment. 
Disease-free survival (DFS) is the primary endpoint of this study. During the follow-up period, 
patients will return to the clinic quarterly until the end of their participation in the study to 
determine if they remain disease free. Patients determined to be disease free will remain on study 
until completion of all their follow-up visits (approximately 24 months from the onset of 
treatment) or until disease recurrence, disease progression, or death is documented, whichever 
comes first. Patients determined to have had a protocol-defined recurrence or progression at any 
follow-up or unscheduled visit will be considered to have completed the study and released to 
the care of their treating physician.  
 
 


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Protocol BL006 version 2.0 
 
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Objectives and Endpoints  
OBJECTIVE 
ENDPOINT 
Primary 
 
To evaluate the efficacy of UGN-102 
with or without TURBT versus 
TURBT alone with respect to disease-
free survival (DFS) in patients with 
Low Grade Intermediate Risk Non-
Muscle Invasive Bladder Cancer 
(LG IR-NMIBC). 
Disease-free survival (DFS) is defined as the time from 
randomization until the earliest date of any of the following 
events: 
• Failure to be rendered free of local disease at the 
3-Month assessment after the TURBT procedure. 
• Recurrence of low-grade disease after the 3-Month 
assessment (i.e., during the follow-up period). 
• Progression to high-grade disease. 
• Death due to any cause. 
Secondary 
 
1. To evaluate the efficacy of 
UGN-102 with or without TURBT 
versus TURBT alone with respect to: 
a) Time to Recurrence (TTR) 
b) Complete Response Rate 
(CRR) at 3-Month disease 
assessment 
c) Duration of Response 
(DOR) 
d) Avoidance of surgery 
(TURBT) for treatment of 
LG IR-NMIBC 
2. To evaluate the safety profile of 
UGN-102 with or without TURBT 
versus TURBT alone. 
3. To assess the effect of UGN-102 
with or without TURBT versus 
TURBT alone on Patient Reported 
Outcomes (PROs) including disease 
related symptoms, functioning, and 
health-related 
quality 
of 
life 
(HRQoL). 
4. To evaluate visit level Complete 
Response Rate (CRR) 
1. The following efficacy endpoints will be evaluated: 
a) Time to recurrence (TTR) is defined as the time from 
randomization until the earliest date of recurrence of 
low-grade disease or progression to high-grade disease. 
b) Complete response rate (CRR), defined as the proportion 
of patients who achieved CR at the 3-Month disease 
assessment.  
c) Duration of response (DOR), defined as the time from 
first documented CR until the earliest date of any of the 
following events: 
• Recurrence of low-grade disease. 
• Progression to high-grade disease. 
• Death due to any cause. 
d) Proportion of patients requiring TURBT in each arm and 
average number of TURBT interventions per patient in 
each arm 
2. The safety profile of UGN-102 and TURBT will be evaluated 
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. 
3. Changes from baseline in HRQoL measures assessed by 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire for Non-muscle Invasive Bladder 
Cancer patients (EORTC-QLQ-NMIBC24). 
4. Observed CRR at scheduled disease assessment timepoints, 
defined as the proportion of patients who had CR at 3-Month 
disease assessment and maintained CR up to that particular 
follow-up disease assessment. 


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Protocol BL006 version 2.0 
 
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OBJECTIVE 
ENDPOINT 
Exploratory  
 
To explore potential differences in 
health 
resource 
utilization 
with 
UGN-102 vs TURBT in patients with 
LG NMIBC 
Number of patients hospitalized for non-elective reasons, total 
number and length of non-elective hospitalizations 
Inclusion Criteria: 
1. Capable of giving signed 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 informed consent. 
3. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed 
by cold cup biopsy at screening or within 8 weeks of screening; 
4. Is at intermediate risk for progression, defined as having 1 or 2 of the following: 
a. presence of multiple tumors 
b. solitary tumor > 3 cm 
c. recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at 
initial Screening Visit) 
5. Negative voiding cytology for high grade (HG) disease within 6 weeks of 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) (Serum glutamic oxaloacetic 
transaminase [SGOT])/Alanine aminotransferase (ALT) (Serum glutamic pyruvic 
transaminase [SGPT]) ≤ 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); 
8. Contraceptive use by men and women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
 
Exclusion Criteria: 
1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of 
enrollment; 
2. Received Bacille de Calmette et Guérin (BCG) treatment for urothelial carcinoma (UC) 
within previous 1 year; 


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Protocol BL006 version 2.0 
 
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3. History of HG papillary UC in the past 2 years; 
4. Known allergy or sensitivity to mitomycin that in the Investigator’s opinion cannot be 
readily managed; 
5. Clinically significant urethral stricture that would preclude passage of a urethral catheter; 
6. History of pelvic radiotherapy; 
7. History of: 
a. neurogenic bladder 
b. active urinary retention 
c. any other condition that would prohibit normal voiding 
8. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic UC or concurrent upper 
tract urothelial carcinoma (UTUC); 
9. Current tumor grading of T1; 
10. 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; 
11. History of prior treatment with an intravesical chemotherapeutic agent except for a single 
dose of chemotherapy immediately post any previous TURBT; 
12. Has previously participated in a study in which they received UGN-102; 
13. Has participated in a study with an investigational agent or device within 30 days of 
randomization. 
Brief Summary: This is a global, randomized, controlled, open-label phase 3 study of UGN-102 
with or without TURBT vs. TURBT alone in the treatment of patients with LG IR-NMIBC. 
Patients will either receive 6 weekly intravesical instillations of UGN-102 followed by TURBT 
only if needed or will undergo TURBT followed by repeat TURBT if needed. Disease-free 
survival is the primary endpoint of this study. Patients will be followed long-term for disease 
recurrence until the end of their participation in the study (i.e., until completion of all follow-up 
visits or until disease recurrence, disease progression, or death is documented). 
Number of Patients: The enrollment of this study has been stopped prematurely by the Sponsor 
in order to pursue an alternative development strategy for UGN-102 in the same patient 
population; 282 eligible patients who were screened on or before 10 Nov 2021 were randomized 
in this study. The study will be conducted primarily by appropriately trained urologists at 
approximately 120 investigative study sites in the United States, Israel, and Europe who provide 
care to patients with bladder cancer. 
Intervention Groups and Duration: 1. UGN-102 (75 mg via intravesical instillation starting at 
Day 1 X 6 weeks) ± TURBT for NCR patients; 2. TURBT alone (Day 1) ± repeat TURBT for 
NCR patients. 
Data Review Committee: Not applicable. 


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1.2. 
Schema 
 


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1.3. 
Schedule of Activities (SoA) – Phase 3 Bladder UGN-102 Patient 
Procedures 
Screen
ing 
Period 
Treatment Period 
WP 
3-M 
DAV 
FUP (Follow-up visits start at Month 6 and continue every 
3 months thereafter until completion of all follow-up visits 
or recurrence/progression/death is documented) a 
Un-
sched
uled 
Screening/ 
Randomiz- 
ationb 
Treatment 
Visitc 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Telephone 
Contact 
Waiting 
Period 
Assessment 
Visitd 
Telephone 
Contact 
Telephone 
Contact
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit (EOS) 
Unscheduled 
Visite 
Visit 
1 
2a 
2b 
2c 
2d 
2e 
2f 
TC
M1  
n/a 
3 
TC
M2 
TC
M3 
4 
5 
6 
7 
8 
9 
10 
n/a 
Day/Week/Month 
D-28 to 
D0 
D1/
W1 
D8/
W2 
D15/
W3 
D22/
W4 
D29/
W5 
D36/
W6 
M2 
W7 
to 
W13 
M3 
M4 
M5 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
n/a 
Window 
n/a 
D0 
+0/+28 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
±1 
wk  
n/a 
±1 
wk 
±1 
wk 
±1 
wk 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
± 2 
wks 
n/a 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QLQ-NMIBC24 
Xf 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/Surgical and 
Smoking History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medication 
review (incl. any past 
therapy related to 
urothelial CA) 
Xg 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urological Exam 
Xh 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology/ 
Serum Chemistry 
(central laboratory) 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
Urinalysisi 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testj 
(WOCBP only) 
X 
X 
 
 
 
 
 
 
 
Xk 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
15 
Procedures 
Screen
ing 
Period 
Treatment Period 
WP 
3-M 
DAV 
FUP (Follow-up visits start at Month 6 and continue every 
3 months thereafter until completion of all follow-up visits 
or recurrence/progression/death is documented) a 
Un-
sched
uled 
Screening/ 
Randomiz- 
ationb 
Treatment 
Visitc 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Treatment 
Visit 
Telephone 
Contact 
Waiting 
Period 
Assessment 
Visitd 
Telephone 
Contact 
Telephone 
Contact
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit (EOS) 
Unscheduled 
Visite 
Visit 
1 
2a 
2b 
2c 
2d 
2e 
2f 
TC
M1  
n/a 
3 
TC
M2 
TC
M3 
4 
5 
6 
7 
8 
9 
10 
n/a 
Day/Week/Month 
D-28 to 
D0 
D1/
W1 
D8/
W2 
D15/
W3 
D22/
W4 
D29/
W5 
D36/
W6 
M2 
W7 
to 
W13 
M3 
M4 
M5 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
n/a 
Window 
n/a 
D0 
+0/+28 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
-1/+3 
d 
±1 
wk  
n/a 
±1 
wk 
±1 
wk 
±1 
wk 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
±2 
wks 
± 2 
wks 
n/a 
Adverse eventsl (incl. 
telephone calls at M2, 
M4, M5 ± 1 week) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CT Urogram, retrograde 
pyelogram or MRIm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cystoscopy (white light) 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Voiding urine cytology 
(send to central 
pathology)n  
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Cold cup biopsy (send to 
central pathology)o  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug administration 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biopsy remaining lesions 
if indicated (send to 
central pathology) 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Complete eCRFs 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
TURBTp 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Abbreviations: 3-M DAV = 3-Month disease assessment visit; AE = adverse event; CA = cancer; CT = computed tomography; d = day; D= Visit Day; eCRF =electronic case 
report form; EOS = end-of-study; FUP = Follow-up Period; ICF = informed consent form; LG = low grade; M = month; MRI = magnetic resonance imaging; n/a = not applicable; 
NCR = Non-complete response; SAE = serious adverse event; TCM = telephone contact month; TURBT = Transurethral Resection of Bladder Tumor; QLQ-NMIBC24 = Quality 
of Life Questionnaire for NMIBC; UGN-102 = UGN-102 (mitomycin) for intravesical solution; UTUC = upper tract urothelial carcinoma; W = Week: wks = weeks; WOCBP = 
women of child-bearing potential; WP = Waiting Period. 
Notes: Primary disease assessment/response evaluation will be performed at the post 3-Month visits in the Follow-up Period.  


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
16 
a. 
For those patients in the follow-up period who have a disease recurrence or progression, the EOS Visit needs to be completed. 
b. 
The screening period is up to 14 days for patients that do not need a screening biopsy and up to 28 days for patients that need a screening biopsy (see Section 8.1.1). 
Randomization should occur after screening evaluations are completed and it is confirmed that the patient qualifies for the study. Every effort should be made to minimize the 
time interval between diagnosis and treatment. Screening procedures are to provide evidence of low grade NMIBC and no evidence of high grade disease. 
c. 
Windows are provided to accommodate patient logistics in scheduling. In any case, instillations should not occur more frequently than 6 days apart. Day 1 does not 
necessarily need to be the day after Day 0 e.g., in the event additional time is required to initiate treatment due to logistics such as scheduling procedure or training for 
UGN-102 instillation. Every effort should be made to minimize the time interval between diagnosis and treatment. 
d. 
Patients who discontinue from the study before the 3-Month Visit should have all assessments specified for the EOS Visit as their EOS assessments. 
e. 
If an unscheduled visit is required, assessments should be performed as appropriate to the needs of the visit, although safety assessments should be performed, if feasible. 
f. 
For baseline score. 
g. 
Any past therapy (e.g. medical or surgical interventions) related to urothelial cancer will be recorded during Screening. 
h. 
Performed prior to cystoscopy at Screening. See Section 8.3.1 for details. 
i. 
Dipstick on-site; culture and sensitivity added at screening if positive for infection (at local laboratory). 
j. 
Urine or serum pregnancy test (at local laboratory). 
k. 
Pregnancy test at assessment visit for NCR patients who will undergo TURBT. 
l. 
All AEs (including local and systemic reactions not meeting the criteria for SAEs) and SAEs will be collected from the signing of the ICF until the Month-6 visit (Visit 4). 
Subsequent to the Month-6 visit, all SAEs (regardless of causality) and non-serious AEs assessed as related to study treatments (UGN-102 or TURBT) or study procedures 
should be collected until the EOS Visit. 
m. CT Urogram, retrograde pyelogram, or MRI (if other tests are contraindicated) to rule out UTUC (acceptable if performed within 6 months of initial Screening Visit) (results 
assessed locally). 
n. 
No cytology needed if results from a prior cytology within 6 weeks of initial Screening Visit are available. 
o. 
Cold cup biopsy to confirm LG tumor performed only if not already performed within 8 weeks of initial Screening Visit. This is a diagnostic biopsy to demonstrate 
histopathology of tumor and resection of tumor is not to be performed. 
p. 
NCR patients at the 3-Month Visit will receive TURBT and enter the FUP. TURBT will be scheduled as soon as possible at Month 3 and every attempt should be made to 
perform TURBT within 1 month of this visit. Note: If the Investigator determines that a formal TURBT in the operating room is unnecessary following cystoscopy and 
biopsy of remaining lesions (e.g., residual disease can be addressed by in office biopsy and/or fulguration), such an alternative procedure is permitted based on the 
Investigator’s medical judgment. 
 
 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
17 
1.4. 
Schedule of Activities (SoA) – Phase 3 Bladder TURBT Patient 
Procedures 
Screen-
ing 
Period 
Treat
ment 
Period 
Wait-
ing 
Period 
Follow-up 
Period 
3-M 
DAV 
Follow-up Period (Follow-up visits start at Month 6 and continue every 
3 months thereafter until completion of all follow-up visits or 
recurrence/progression/death is documented)a 
Un-
sched
uled 
Screening/
Randomiz-
ationb 
Treatment 
Visit c 
Waiting 
Period 
Telephone 
Contact 
Telephone 
Contact 
Assessment 
Visitd 
Telephone 
Contact 
Telephone 
Contact 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit (EOS) 
Unscheduled 
Visite 
Visit 
1 
2 
n/a 
TCM1 
TCM2 
3 
TCM3 
TCM4 
4 
5 
6 
7 
8 
9 
10 
n/a 
Day/Week/Month 
D-28 to 
D0 
D1/W1 
W2 to 
W13 
M1 
M2 
M3 
M4 
M5 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
n/a 
Window 
n/a 
D0 
+0/+28 d 
n/a 
±1 wk 
±1 wk 
±1 wk 
±1 wk 
±1 wk 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
n/a 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QLQ-NMIBC24 
Xf 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/Surgical and 
Smoking History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medication 
review (incl. any past 
therapy related to 
urothelial CA) 
Xg 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urological Exam 
Xh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology/ 
Serum chemistry 
(central laboratory) 
X 
X 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
Urinalysisi 
X 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testj 
(WOCBP only) 
X 
X 
 
 
 
Xk 
 
 
 
 
 
 
 
 
 
 
Adverse eventsl (incl. 
telephone calls at M1, 
M2, M4, M5 ± 1 week) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
18 
Procedures 
Screen-
ing 
Period 
Treat
ment 
Period 
Wait-
ing 
Period 
Follow-up 
Period 
3-M 
DAV 
Follow-up Period (Follow-up visits start at Month 6 and continue every 
3 months thereafter until completion of all follow-up visits or 
recurrence/progression/death is documented)a 
Un-
sched
uled 
Screening/
Randomiz-
ationb 
Treatment 
Visit c 
Waiting 
Period 
Telephone 
Contact 
Telephone 
Contact 
Assessment 
Visitd 
Telephone 
Contact 
Telephone 
Contact 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit 
Follow-up 
Visit (EOS) 
Unscheduled 
Visite 
Visit 
1 
2 
n/a 
TCM1 
TCM2 
3 
TCM3 
TCM4 
4 
5 
6 
7 
8 
9 
10 
n/a 
Day/Week/Month 
D-28 to 
D0 
D1/W1 
W2 to 
W13 
M1 
M2 
M3 
M4 
M5 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
n/a 
Window 
n/a 
D0 
+0/+28 d 
n/a 
±1 wk 
±1 wk 
±1 wk 
±1 wk 
±1 wk 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
±2 wks 
n/a 
CT Urogram, retrograde 
pyelogram or MRIm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cystoscopy (white light) 
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Voiding urine cytology 
(send to central 
pathology) n  
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Cold cup biopsy (send to 
central pathology) o  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biopsy remaining lesions 
if indicated (send to 
central pathology) 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Complete eCRFs 
X 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
TURBT 
 
X 
 
 
 
Xp 
 
 
 
 
 
 
 
 
 
 
Abbreviations: 3-M DAV = 3-Month disease assessment visit; AE = adverse event; CA = cancer; CT = computed tomography; d = day; D= Visit Day; eCRF =electronic case 
report form; EOS = end-of-study; FUP = Follow-up Period; ICF = informed consent form; LG = low grade; M = month; MRI = magnetic resonance imaging; n/a = not applicable; 
NCR = Non-complete response; SAE = serious adverse event; TCM = telephone contact month; TURBT = Transurethral Resection of Bladder Tumor; QLQ-NMIBC24 = Quality 
of Life Questionnaire for NMIBC; UGN-102 = UGN-102 (mitomycin) for intravesical solution; UTUC = upper tract urothelial carcinoma; W = Week: wks = weeks; WOCBP = 
women of child-bearing potential. 
Notes: Primary disease assessment/response evaluation will be performed at the post 3-Month visits in the Follow-up Period.  
a. 
For those patients in the follow-up period who have a disease recurrence or progression, the EOS Visit needs to be completed. 
b. 
The screening period is up to 14 days for patients that do not need a screening biopsy and up to 28 days for patients that need a screening biopsy (see Section 8.1.1). 
Randomization should occur after screening evaluations are completed and it is confirmed that the patient qualifies for the study. Every effort should be made to minimize the 
time interval between diagnosis and treatment. Screening procedures are to provide evidence of low grade NMIBC and no evidence of high grade disease. 
c. 
Windows are provided to accommodate patient logistics in scheduling. Day 1 does not necessarily need to be the day after Day 0, e.g., in the event additional time is required 
to initiate treatment due to logistics such as scheduling procedure. Every effort should be made to minimize the time interval between diagnosis and treatment. 
d. 
Patients who discontinue from the study before the 3-Month Visit should have all assessments specified for the EOS Visit as their EOS assessments. 
e. 
If an unscheduled visit is required, assessments should be performed as appropriate to the needs of the visit, although safety assessments should be performed, if feasible. 
f. 
For baseline score. 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
19 
g. 
Any past therapy (e.g., medical or surgical interventions) related to urothelial cancer will be recorded during Screening. 
h. 
Performed prior to cystoscopy at Screening. See Section 8.3.1 for details. 
i. 
Dipstick on-site; culture and sensitivity added at screening if positive for infection (at local laboratory). 
j. 
Urine or serum pregnancy test (at local laboratory). 
k. 
Pregnancy test at assessment visit for NCR patients who will undergo TURBT. 
l. 
All AEs (including local and systemic reactions not meeting the criteria for SAEs) and SAEs will be collected from the signing of the ICF until the Month-6 visit (Visit 4). 
Subsequent to the Month-6 visit, all SAEs (regardless of causality) and non-serious AEs assessed as related to study treatments (UGN-102 or TURBT) or study procedures 
should be collected until the EOS Visit. 
m. CT Urogram, retrograde pyelogram, or MRI (if other tests are contraindicated) to rule out UTUC (acceptable if performed within 6 months of initial Screening Visit) (results 
assessed locally). 
n. 
No cytology needed if results from a prior cytology within 6 weeks of initial Screening Visit are available. 
o. 
Cold cup biopsy to confirm LG tumor performed only if not already performed within 8 weeks of initial Screening Visit. This is a diagnostic biopsy to demonstrate 
histopathology of tumor and resection of tumor is not to be performed. 
p. 
NCR patients at the 3-Month Visit will receive another TURBT and enter the FUP. TURBT will be scheduled as soon as possible at Month 3 and every attempt should be 
made to perform TURBT within 1 month of this visit. Note: If the Investigator determines that a formal TURBT in the operating room is unnecessary following cystoscopy 
and biopsy of remaining lesions (e.g., residual disease can be addressed by in office biopsy and/or fulguration), such an alternative procedure is permitted based on the 
Investigator’s medical judgment. 
 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
20 
Abbreviations 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
ALP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase 
BCG 
Bacille de Calmette et Guérin 
CBC 
Complete blood count 
CCGs 
CRF Completion Guidelines 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CIS 
Carcinoma in situ 
CONSORT 
Consolidated Standards of Reporting Trials 
CR 
Complete response 
CRO 
Contract Research Organization 
CRR 
Complete response rate 
CT 
Computerized tomography 
CTA 
Clinical Trial Agreement 
CTCAE 
Common Terminology Criteria for Adverse Events 
DFS 
Disease-free survival 
DOR 
Duration of response 
DRC 
Data Review Committee 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOS 
End-of-Study 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyltransferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HG 
High grade 
HIPAA 
Health Insurance Portability and Accountability Act 
HRQoL 
Health Related Quality of Life 
HR 
Hazard Ratio 
IB 
Investigator’s Brochure 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
21 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFA 
Instructions for Administration 
IFP 
Instructions for Pharmacy 
IND 
Investigational New Drug 
IP 
Investigational Product 
IQR 
Interquartile range 
IR 
Intermediate Risk 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
LG 
Low grade 
LPLV 
Last patient last visit 
LUTS 
Lower urinary tract symptoms 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed effect model for repeated measures 
MRI 
Magnetic resonance imaging 
NCI 
National Cancer Institute 
NDD 
No detectable disease 
NI 
Non-inferiority 
NMIBC 
Non-muscle invasive bladder cancer 
NCR 
Non-complete response 
PCS 
Potentially clinically significant 
PI 
Principal Investigator 
PPS 
Per Protocol Set 
PQC 
Product Quality Complaint 
PRO 
Patient reported outcome 
PT 
Preferred Term 
PUNLMP 
Papillary Urothelial Neoplasm of Low Malignant Potential 
QLQ 
Quality of Life Questionnaire 
QLQ-NMIBC24 
Quality of Life Questionnaire for NMIBC 
QC 
Quality control 
QLTs 
Quality tolerance limits 
QoL 
Quality-of-Life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SMP 
Study Monitoring Plan 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
22 
SoA 
Schedule of Activities 
SoC 
Standard of care  
SOP 
Standard Operating Procedure 
SRT 
Safety Review Team. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment-emergent adverse event 
TNM 
Tumor-Node-Metastases 
TTR 
Time to recurrence 
TURBT 
Transurethral resection of bladder tumor 
UADR 
Unexpected Adverse Drug Reaction 
UC 
Urothelial carcinoma/cancer 
UGN-102 
UGN-102 (mitomycin) for intravesical solution 
US 
United States 
USP 
United States Pharmacopeia 
UTI 
Urinary tract infection 
UTUC 
Upper tract urothelial carcinoma 
WHO 
World Health Organization 
WOCBP 
Women of child-bearing potential 
 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
23 
2. 
Introduction 
Non-Muscle Invasive Bladder Cancer 
Urothelial cancer (UC) of the bladder is the second most common genitourinary malignancy in 
the United States (US), with an estimated 81,400 new cases diagnosed and 18,000 deaths from 
the disease in 2020 (ACS, 2020). Non-muscle invasive bladder cancer (NMIBC) accounts for 
about 80% of all bladder cancers (Kirkali, 2005). Patients with NMIBC can be segmented into 
3 staging groups: patients with Ta tumors (70%), patients with T1 tumors (20%), and patients 
with carcinoma in situ (CIS) or Tis tumors (10%). Of these patients, approximately 70% have a 
tumor that is classified as low grade (LG), and approximately 30% have a tumor that is classified 
as high grade (HG). Ta and CIS tumors are limited to the urothelial layer, and T1 is limited to the 
lamina propria. 
The standard treatment of NMIBC is transurethral resection of bladder tumor (TURBT) (Pereira, 
2019). TURBT is associated with the typical risks of surgery including injury to the bladder and 
postoperative bleeding. Recurrence rates following standard of care (SoC) management range from 
31% to 78% with the risk of progression to muscle invasion approaching 50% in patients with 
HG cancer (Babjuk, 2019). Tumor recurrence following TURBT can be attributed primarily to 
incomplete initial resection and, at least hypothetically, to tumor cell reimplantation following 
surgery (Anastasiadis, 2012; Brausi, 2002; Miladi, 2003). The effectiveness of intravesical therapy 
is limited by urine production, which results in drug dilution and periodic bladder emptying, and 
which limits the agent’s time on target (Audenet, 2013; Dalton, 1991; Wientjes, 1991). 
Chemoablation represents an attractive alternative to surgical therapy. It could avoid the 
morbidity and expense of surgery and may offer a more rational therapeutic approach to UC, 
which is generally multifocal and refractory to focal ablative interventions. Preliminary evidence 
documents the ablative capabilities of aqueous Mitomycin C, which has been applied 
successfully to the primary management of small UCs (Colombo, 2001; Gontero 2004, 
Maffezzini, 2007; Racioppi, 2010). 
UGN-102 
UroGen has performed two Phase 2a open-label dose-escalation studies (Study BL002, BL004) 
and one Phase 2 open-label active-control study (Study BL003) which showed a favorable safety 
and efficacy profile for UGN-102 in patients with LG NMIBC. Based on this initial experience, 
UroGen also conducted a Phase 2b UGN-102 study (Study BL005) in the US and Israel to 
corroborate the prior data and to determine pharmacokinetic parameters. Results from this Phase 
2b study showed a complete response rate (CRR) of 65% (41/63) at 3 months after the first 
instillation of UGN-102, of which 61% (25/41) remained free of disease at 12 months after the 
first instillation of UGN-102. 
Results to date from clinical studies are supportive for the determination of the long-term safety 
and efficacy profile of UGN-102 in the LG NMIBC with intermediate risk (IR) indication under 
the overall clinical development strategy for UGN-102. 


CONFIDENTIAL 
Protocol BL006 version 2.0 
 
24 
2.1. 
Study Rationale 
Study BL006 
This study is a global, randomized, controlled, open-label Phase 3 study to evaluate the 
long-term efficacy and safety of intravesical UGN-102 given once weekly for a total of 6 doses 
in the treatment of patients with Low Grade Intermediate Risk Non-Muscle Invasive Bladder 
Cancer (LG IR-NMIBC). This study seeks to establish the efficacy of UGN-102 as a primary 
chemoablative therapy in the treatment of LG IR-NMIBC. The study models the clinical practice 
of neoadjuvant therapy in the subset of patients who do not achieve a complete response (CR) 
after receiving UGN-102 (i.e., when assessed at 3 months); such patients in clinical practice 
would be treated with TURBT per SoC. In addition, the study designates TURBT alone patients 
as a comparison population for patients treated with UGN-102 (with or without TURBT). 
The BL006 study is supported by the results of a Phase 2b study (Study BL005) in patients with 
LG IR NMIBC. The favorable benefit-risk profile of UGN-102 observed in this study, including 
high rates of complete response (CR) and durable complete response (DCR), primarily mild to 
moderate adverse events (AEs), no treatment-related serious adverse events (SAEs) or 
hospitalizations, low number of treatment discontinuations, no organ dysfunction, and no adverse 
impact on health-related quality of life (HRQoL), suggests that treatment with UGN-102 may 
obviate the need for surgery in some patients and result in fewer clinically significant adverse 
effects than TURBT. 
Background 
UGN-102 consists of mitomycin for solution (40 mg x 2) and sterile hydrogel (a proprietary 
thermally responsive gel, 60 mL) to produce UGN-102 for subsequent intravesical installation 
via a sterile catheter. Upon reconstitution, UGN-102 will be administered to patients at a 
concentration of 1.33 mg/mL (56 mL instillation volume for a total of 75 mg mitomycin per 
dose). The product is administered as a liquid and solidifies in the bladder to create a drug depot, 
which retains the mitomycin longer at the target site of administration. The advantage of 
delivering mitomycin to the urinary bladder using UGN-102 relies on preclinical and clinical 
literature documenting that concentration and dwell time correlate directly with the therapeutic 
efficacy of mitomycin when used to treat UC (Barlogie, 1980; Slee, 1986; Walker, 1986; Ozawa, 
1988; Perry, 1992; Nozue, 1995; Sadeghi, 1998). 
Mitomycin functions as a bifunctional or trifunctional alkylating agent. It is most sensitive in the 
late G1 and early S phases, but overall is considered cell cycle phase non-specific (Badalament, 
1997). The cell killing induced by mitomycin, as well as by other topical chemotherapy drugs, is 
proportional to the duration of exposure and to concentration (Serreta, 2008; De Bruijn, 1992; 
Sadeghi, 1998; Barlogie, 1980; Nozue, 1995; Schmittgen, 1991; Ozawa, 1988; Walker, 1986; 
Slee, 1986; Giesbers, 1989).  
UGN-102 Investigational Product 
UGN-102 is provided by UroGen as a single dose carton containing 2 vials of 40 mg mitomycin 
for solution, and one 60 mL vial of sterile hydrogel. The proprietary hydrogel, allows for a 
sustained release of mitomycin at the target site of administration, resulting in prolonged 
exposure of the tumor cells to mitomycin, where it can exert a chemical ablative effect. 


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25 
Ancillaries required for admixture and administration of UGN-102 are shipped to clinical sites in 
separate boxes. 
Preclinical studies of UGN-102 performed by UroGen demonstrated limited systemic absorption 
of mitomycin. In a porcine model, all mitomycin plasma concentrations were found to be 
substantially below 400 ng/mL, which is the drug concentration associated with 
myelosuppression (Dalton, 1991). In clinical studies, systemic levels of mitomycin were low and 
well-tolerated within the range considered safe. Systemic toxicity following intravesical therapy 
is uncommon because of the limited absorption of mitomycin. Myelosuppression occurs in < 1% 
of patients (De Bruijn, 1992). Investigators have reported that extended dwell times appear safe 
in humans (De Bruijn, 1992). 
For further details of the preclinical and clinical studies conducted with UGN-102, refer to the 
Investigator’s Brochure (IB) for UGN-102. 
2.2. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of UGN-102 may be found in the IB. 
2.2.1. 
Risk Assessment 
Cystitis and Lower Urinary Tract Symptoms (LUTS) 
Cystitis and other lower urinary tract symptoms (LUTS) may develop. Urine tests, including 
urinalysis and urine culture where indicated, will be checked regularly during the study to 
exclude urinary infection. Any symptoms will be treated by the Investigator according to local 
practice.  
All of the symptoms described above are all well known in relation to standard mitomycin 
instillations and are not specific to UGN-102.  
Currently, the SoC for NMIBC is TURBT. This surgical procedure has its own potential risks 
such as bladder perforation resulting in mitomycin leak, bladder scarring, and decreased bladder 
capacity; urinary retention requiring catheterization; and the need for anesthesia.  
Moreover, during TURBT, tumor cells are released into the bladder cavity and may be seeded in 
denuded areas of the bladder where the urothelium is surgically interrupted. This is one of the 
reasons for the high rate of tumor recurrence and the use of immediate post-TURBT 
chemotherapy (usually mitomycin instillations). The high recurrence rate of NMIBC indicates 
that the current SoC is far from optimal. 
Toxicity Associated with Systemic Absorption/Local Irritation 
Although literature review did not demonstrate any side effects associated with the systemic 
absorption when mitomycin was administered topically, bone marrow toxicity 
(thrombocytopenia and leukopenia) and bladder toxicity are considered possible risks for 
patients. The complete blood count (CBC) and renal and liver function tests will be checked 
regularly during the treatment period. In case of clinically significant abnormalities, the 
Investigator will continue to follow the abnormal parameter until resolution, stabilization, or 
otherwise managed.  


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Allergic Response to Mitomycin 
Mitomycin bladder instillations have been shown to cause allergic reactions in various degrees of 
toxicity in treated patients. Toxicities were found to be manageable most of the time by treating 
the patients with antihistamine drugs prior to and after the treatment, and with systemic steroids 
as needed. Signs of an allergic response will be closely monitored during the study. 
Coronavirus Disease 2019 (COVID-19) 
The COVID-19 pandemic has caused patients with cancer to confront the competing risks of 
potential COVID-19 exposure and delay in effective cancer treatment. Due to limited data, there 
are no international guidelines to address the management of cancer patients in an infectious 
pandemic. Therefore, consideration of risk and benefit for active intervention in the cancer 
population must be individualized. 
There are no temporary or permanent requirements in the study for additional tests or procedures 
due to the COVID-19 pandemic unless they are required by local and/or hospital regulations. 
Any additional local COVID-19 related procedures (e.g., COVID-19 testing for patients to attend 
site visits or undergo procedures related to this study) may be implemented at the discretion of 
the Investigator. 
Patients may receive authorized COVID-19 vaccines while participating in the study, including 
those granted emergency use authorization, but cannot participate in any investigational 
COVID-19 vaccine or other trials within 30 days of randomization or during study conduct. 
2.2.2. 
Benefit Assessment 
The potential advantages of instillation of mitomycin in hydrogel are as follows: 
• Extended exposure of drug for up to 8 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. 
2.2.3. 
Overall Benefit: Risk Conclusion 
The potential benefits exceed the risks observed so far in the development program. Since the 
risks are similar to those observed with intravesical mitomycin alone, and the expected benefits 
are to improve mitomycin’s therapeutic efficacy and to expand its use, the overall benefit:risk 
ratio at this stage supports continued development of UGN-102. 
 


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3. 
Objectives and Endpoints 
 
OBJECTIVE 
ENDPOINT 
Primary 
 
To evaluate the efficacy of UGN-102 
with or without TURBT versus 
TURBT alone with respect to disease-
free survival (DFS) in patients with 
Low Grade Intermediate Risk Non-
Muscle Invasive Bladder Cancer 
(LG IR-NMIBC). 
Disease-free survival (DFS) is defined as the time from 
randomization until the earliest date of any of the following 
events: 
• Failure to be rendered free of local disease at the 
3-Month assessment after the TURBT procedure. 
• Recurrence of low-grade disease after the 3-Month 
assessment (i.e., during the follow-up period). 
• Progression to high-grade disease. 
• Death due to any cause. 
Secondary 
 
1. To evaluate the efficacy of 
UGN-102 with or without TURBT 
versus TURBT alone with respect to: 
a) Time to Recurrence (TTR) 
b) Complete Response Rate 
(CRR) at 3-Month disease 
assessment 
c) Duration of Response 
(DOR) 
d) Avoidance of surgery 
(TURBT) for treatment of 
LG IR-NMIBC 
2. To evaluate the safety profile of 
UGN-102 with or without TURBT 
versus TURBT alone  
3. To assess the effect of UGN-102 
with or without TURBT versus 
TURBT alone on Patient Reported 
Outcomes (PROs) including disease 
related symptoms, functioning, and 
health-related 
quality 
of 
life 
(HRQoL) 
4. To evaluate visit level Complete 
Response Rate (CRR) 
 
 
1. The following efficacy endpoints will be evaluated: 
a) Time to recurrence (TTR) is defined as the time from 
randomization until the earliest date of recurrence of low-
grade disease or progression to high-grade disease.  
b) Complete response rate (CRR), defined as the proportion 
of patients who achieved CR at the 3-Month disease 
assessment. 
c) Duration of response (DOR), defined as the time from 
first documented CR until the earliest date of any of the 
following events: 
• Recurrence of low-grade disease. 
• Progression to high-grade disease. 
• Death due to any cause. 
d) Proportion of patients requiring TURBT in each arm and 
average number of TURBT interventions per patient in 
each arm 
2. The safety profile of UGN-102 and TURBT will be evaluated 
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. 
3. Changes from baseline in HRQoL measures assessed by 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire for Non-muscle Invasive Bladder 
Cancer patients (EORTC-QLQ-NMIBC24). 
4. Observed CRR at scheduled disease assessment timepoints, 
defined as the proportion of patients who had CR at 3-Month 
disease assessment and maintained CR up to that particular 
follow-up disease assessment. 


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OBJECTIVE 
ENDPOINT 
Exploratory  
 
To explore potential differences in 
health 
resource 
utilization 
with 
UGN-102 vs TURBT in patients with 
LG NMIBC 
Number of patients hospitalized for non-elective reasons, total 
number and length of non-elective hospitalizations 


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4. 
Study Design 
4.1. 
Overall Design 
This study is a global, randomized, controlled, open-label Phase 3 study designed to assess the 
long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution (i.e., intravesical 
instillation) with or without TURBT versus TURBT alone in the treatment of patients with LG 
IR-NMIBC defined as 1 or 2 of the following: multiple tumors, solitary tumor > 3 cm, or 
recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial 
Screening Visit) (Kamat, 2014). Eligible patients will be treated with 6 weekly instillations of 
UGN-102 followed by TURBT only if needed, or with TURBT alone. 
Upon signing of informed consent patients will undergo a Screening Visit for eligibility 
evaluation. The screening period is 2 weeks if the patient’s cold cup biopsy to confirm whether 
the LG tumor is historic (taken within 8 weeks of the Screening Visit) or 4 weeks if the patient’s 
cold cup biopsy to confirm LG tumor is current (taken at the Screening Visit). Every effort 
should be made to minimize the time interval between diagnosis and treatment. 
Eligible patients will be randomized in a 1:1 ratio to UGN-102 with or without TURBT or 
TURBT alone. Randomization will be stratified by the presence of previous LG NMIBC 
episodes within 1 year of the current diagnosis at the initial Screening Visit (yes versus no). 
Starting at Day 1, patients randomized to the UGN-102 group will receive 6 weekly intravesical 
instillations of UGN-102 followed by TURBT only if needed and patients randomized to the 
TURBT alone group will undergo TURBT followed by repeat TURBT if needed. The UGN-102 
concentration to be used in this study will be 1.33 mg mitomycin per 1 mL. The volume of 
UGN-102 to be instilled will be 56 mL (75 mg of mitomycin). 
Patients will enter a Waiting Period after receiving their last dose of study intervention in the 
Treatment Period. All patients (i.e., both treatment arms) will return to the clinic at 
approximately 3 months from the initiation of treatment (i.e., 7 weeks ±1 week after the last 
weekly instillation for the UGN-102 treatment arm; and 12 weeks ±1 week after TURBT for the 
TURBT alone treatment arm) for determination of response to ablative treatment. Following this 
initial evaluation, all patients confirmed to have had a CR will receive no further treatment and 
will enter the follow-up period of the study. Patients confirmed to have had a non-complete 
response (NCR) in either treatment arm will undergo TURBT of any remaining lesions and will 
then also enter the follow-up period of the study. Note: If the Investigator determines that a 
formal TURBT in the operating room is unnecessary following cystoscopy and biopsy of 
remaining lesions (e.g., residual disease can be addressed by in office biopsy and/or fulguration), 
such an alternative procedure is permitted based on the Investigator’s medical judgment. 
Response will be determined based on visual evaluation by cystoscopy (white light) (appearance, 
number, and size of any remaining lesions), histopathology of any remaining lesions, and 
voiding urine cytology. CR is defined as having no detectable disease (NDD) in the bladder and 
will be assessed visually via cystoscopy and by interpretation of urine cytology, and if indicated, 
biopsy results. Any lesions or suspect tissue must be biopsied to exclude recurrence. 
During the follow-up period, patients will return to the clinic quarterly (e.g., at Months 6, 9, 12, 
15, 18, 21, 24) until the end of their participation in the study to determine if they remain disease 
free. Patients determined to be disease free will remain on study until completion of all their 


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30 
follow-up visits (approximately 24 months from the onset of treatment) or until disease 
recurrence, disease progression, or death is documented, whichever comes first. Patients 
determined to have had a protocol-defined recurrence or progression at any follow-up or 
unscheduled visit will be considered to have completed the study and released to the care 
(i.e., SoC) of their treating physician. 
A patient will be considered to have completed the study if the patient completes all follow-up 
visits in accordance with the Schedule of Activities (SoA), has a recurrence or progression 
during the follow-up period, dies during the study, or is still in follow-up when End-of-Study 
(EOS) is declared. 
Safety will be evaluated based on 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 8.4.2.3.3), and 
qualified per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) as Grade 3 or 4 (Section 8.4.2.3.1 and Section 8.4.10). 
4.2. 
Scientific Rationale for Study Design 
The randomized, controlled, open-label design was chosen to confirm the results of Study 
BL005. Results from Study BL005 indicate that a dose regimen of 6 weekly instillations of 
UGN-102 (75 mg mitomycin) is effective and well tolerated in patients with LG NMIBC. Study 
BL005 which treated the LG IR-NMIBC population showed a CRR of 65% at 3 months after the 
first instillation of UGN-102 with 61% of CR patients remaining disease free at 12 months after 
the first instillation of UGN-102. The most commonly reported AEs (≥ 10% of patients) were 
dysuria, pollakiuria, hematuria, micturition urgency, urinary tract infection (UTI), and fatigue. 
4.2.1. 
Patient Input into Design 
Not applicable. 
4.3. 
Justification for Dose 
The UGN-102 dose of 75 mg was chosen based on both efficacy and tolerability. Study BL003 
demonstrated 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 to 75 mg and a higher rate of AEs 
(100% of patients in the 120 mg group); the 120 mg dose did not appear to have any added 
efficacy over 75 mg in the treatment of patients with NMIBC. Study BL005 showed a favorable 
efficacy and safety profile with 6 weekly instillations at 75 mg dose. Results showed a 
considerable treatment response with encouraging durability. The dose was considered well-
tolerated and safe with 64% of patients showing study drug or procedure-related AEs. 
For this randomized, controlled, open-label study (BL006), patients who do not achieve CR after 
6 weekly instillations of UGN-102 75 mg will be treated with TURBT and then enter the 
follow-up phase of the study. In the event of recurrence in the follow-up phase, patients will exit 
the study to be treated according to SoC by their treating physician. 


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4.4. 
End-of-Study Definition 
The end of the study is defined as the last patient’s last visit (LPLV). 
EOS will be declared after all patients have completed the EOS Visit, died during the study, 
withdrawn consent, been lost to follow-up, or when the study is closed by the Sponsor. 
4.5. 
Patient Completion and Withdrawal 
A patient will be considered to have completed the study if the patient completes all follow-up 
visits in accordance with the SoA, has a recurrence or progression during the follow-up period, 
dies during the study, or is still in follow-up when EOS is declared. 
A patient will be considered to have withdrawn from the study if the patient has not recurred, 
progressed, or died and is lost to follow-up, has withdrawn consent, is no longer being followed 
at the Investigator’s discretion, or if the study is closed or terminated. 
Refer further to details provided in Section 7. 


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5. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Patients are eligible to be included in the study only if all of the following criteria apply: 
Informed Consent 
1. Capable of giving signed informed consent as described in Section 10.1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
Age 
2. Patient must be ≥ 18 years of age, at the time of signing the informed consent. 
Type of Patient and Disease Characteristics 
3. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed 
by cold cup biopsy at screening or within 8 weeks of screening; 
4. Is at intermediate risk for progression, defined as having 1 or 2 of the following: 
a. presence of multiple tumors 
b. solitary tumor > 3 cm 
c. 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 of 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) (Serum glutamic oxaloacetic 
transaminase [SGOT])/Alanine aminotransferase (ALT) (Serum glutamic pyruvic 
transaminase [SGPT]) ≤ 2.5 × ULN 
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN 
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 
7. Has no evidence of active UTI. 


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Sex and Contraceptive/Barrier Requirements 
8. Both male and female patients 
Contraceptive use by men and women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
a. Female partner of male patient: 
Willing to use 2 acceptable forms of effective contraception from enrollment through 
6 months post treatment if the patient is the female partner of a male patient of 
childbearing potential (defined as premenopausal women who have not been 
sterilized). 
Acceptable methods of birth control which are considered to have a low failure rate 
(i.e., less than 1% per year) when used consistently and correctly, such as implants, 
injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine 
devices (IUDs-only hormonal), condoms with spermicide, sexual abstinence* or 
vasectomized partner. 
* Sexual abstinence is defined as refraining from intercourse from enrollment 
through 6 months post treatment. Periodic abstinence (calendar, symptothermal, 
post-ovulation methods) is NOT an acceptable method of contraception. 
b. Female patient: 
Willing to use 2 acceptable forms of effective contraception from enrollment through 
6 months post treatment if the patient is female of childbearing potential (defined as 
premenopausal women who have not been sterilized). 
 
5.2. 
Exclusion Criteria  
Patients are excluded from the study if any of the following criteria apply: 
Medical Conditions and Diagnostic Assessments 
1. History of CIS on preliminary cystoscopy within 5 years of enrollment; 
2. Received Bacille de Calmette et Guérin (BCG) treatment for UC within previous 
1 year; 
3. History of HG papillary UC in the past 2 years; 
4. Known allergy or sensitivity to mitomycin that in the Investigator’s opinion cannot be 
readily managed; 
5. Clinically significant urethral stricture that would preclude passage of a urethral 
catheter; 
6. History of pelvic radiotherapy; 


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7. History of: 
a. neurogenic bladder 
b. active urinary retention 
c. any other condition that would prohibit normal voiding 
8. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic UC or concurrent upper 
tract urothelial carcinoma (UTUC); 
9. Current tumor grading of T1; 
Compliance Assessment  
10. 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; 
Prior/Concomitant Therapy 
11. History of prior treatment with an intravesical chemotherapeutic agent except for a 
single dose of chemotherapy immediately post any previous TURBT; 
Prior/Concurrent Clinical Study Experience 
12. Has previously participated in a study in which they received UGN-102; 
13. Has participated in a study with an investigational agent or device within 30 days of 
randomization. 
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomly assigned to study intervention. 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 (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). Re-screening of 
patients is allowed in this study. 
5.5. 
Strategies for Recruitment and Retention 
The enrollment of this study has been stopped prematurely by the Sponsor in order to pursue an 
alternative development strategy for UGN-102 in the same patient population; 282 eligible patients 
who were screened on or before 10 Nov 2021 were randomized in this study. The study will be 
conducted primarily by appropriately trained urologists at approximately 120 investigative study 
sites in the United States, Israel, and Europe who provide care to patients with bladder cancer. 


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5.6. 
Criteria for Temporarily Delaying Administration of Study 
Intervention Administration 
If at any time the Investigator identifies myelosuppression, evidence of active UTI, or other 
significant clinical event or laboratory derangements during the study outside the pre-defined 
parameters, treatment may be postponed for up to 4 weeks until clinical event resolves and/or 
laboratory values improve (See Section 8.3.3.1).  


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6. 
Study Intervention(s) and Concomitant Therapy 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study patient according to the 
study protocol. 
6.1. 
Study Intervention(s) Administered 
6.1.1. 
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 qualified location for drug preparation (typically 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. The UGN-102 
single dose carton contains the below listed components (see Table 1): 
Table 1: 
UGN-102 Components 
Component 
Quantity (per 
single dose carton) † 
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 
Abbreviations: WFI = water for injection. 
† For the proposed indication, each 40 mg 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. 
 
Chemical name: 7-amino-9α-methoxymitosane 
Formula: C15H18N4O5 
Molecular weight: 334.33 g/mol 
CASRN: 50-07-7 


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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. 
6.1.2. 
Admixture and Administration Ancillary Supplies 
All ancillary supplies used to prepare and administer the study treatment are detailed in the 
Instructions for Administration (IFA) and Instructions for Pharmacy (IFP). 
6.1.3. 
Dosing and Administration 
The patients entering this study will undergo 6 weekly instillations of UGN-102 if randomized to 
the UGN-102 treatment arm. 
Mitomycin 
concentration 
UGN-102 volume 
Route of administration* 
1.33 mg/mL 
56 mL 
Local administration into the bladder 
* Refer to UGN-102 Instructions for Administration (IFA) for detailed instillation instructions. 
UGN-102 will be administered for therapy in the bladder as 6 weekly, consecutive instillations, 
at Study Visits 2a-2f (UGN-102 ± TURBT). Study treatment administration will be documented 
in the patient file, electronic Case Report Forms (eCRFs), and in the Drug Administration 


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Records. Patients randomized to the TURBT arm will undergo TURBT and will not receive 
UGN-102 during the study. 
Hospitalization is not a requirement for this study. Patients will be admitted to and discharged 
from the hospital at the discretion of the Investigator. UGN-102 instillations are expected to 
occur at the study site on an ambulatory basis (Section 8.1.2). TURBT will be performed either 
as an ambulatory or an inpatient procedure according to the local standards of the study site. 
6.1.4. 
Preparation and Administration Supplies 
Preparation and administration supplies (or supplies manufactured for UroGen Pharma Ltd by a 
third party) provided for use in this study are: 
Catalog number 
Description 
Manufacturer 
 
 
 
 
 
 
Other preparation and administration supplies (not manufactured by or for UroGen Pharma Ltd) 
provided for use in this study are: 
Catalog number 
Description 
Manufacturer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.2. 
Admixture/Handling/Storage/Accountability 
6.2.1. 
Acquisition and Accountability 
UGN-102 single-dose carton is assembled for UroGen Pharma Ltd. 9 Ha’Ta’asiya St., Ra’anana, 
Israel by
 All clinical supplies will be packaged and labeled in compliance with GMP 
guidelines. The shipment process should comply with the rules of Good Distribution Practices. 
Prior to shipment of clinical supplies, the Sponsor or Sponsor’s Designee should notify the 
Principal Investigator (PI) regarding the anticipated date of arrival at the hospital/clinic 
pharmacy. The investigational product (IP) will be sent to the site only after study approval by 
the Institutional Review Board (IRB) has been received. The shipment will be sent to the 
Investigator’s authorized study personnel at the site’s pharmacy. 
All dispensed study treatments will be appropriately documented to ensure proper handling in 
case of emergency. 
The Sponsor’s Designee will ship all drugs to the pharmacy/approved designee at a controlled 
temperature between 15°C and 30°C (59°F and 86°F). The shipping temperature will be 
monitored and recorded by temperature-monitoring device loggers. 
If, upon arrival, the IP supplies appear to be damaged or the temperature was above or below the 
specified limit during shipment, the clinical site pharmacy will contact and report the issue 
immediately according to the product quality complaint (PQC) procedure described in 
Section 6.2.5. The impacted IP must be marked “not for use” and quarantined during 
investigation until a decision has been made regarding the drug’s validity. 
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 CRA, 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.  


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6.2.2. 
Formulation, Appearance, Packaging, and Labeling 
The formulation of the study treatment and the contents of UGN-102 is described in 
Section 6.1.1. All clinical supplies will be packaged and labeled in compliance with GMP 
guidelines. All information regarding study treatment provided will be appropriately documented 
(i.e., batch records, Certificate of Analysis, etc.). The original product packaging will be used in 
the study (UroGen Pharma Ltd., Israel). 
6.2.3. 
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 study 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. 
6.2.4. 
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 from the point the mixture is prepared 
until it is instilled, which includes the length of time at room temperature, as well as length of 
time at a refrigerated temperature. 
6.2.5. 
Product Quality Complaint Handling 
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or 
packaging; i.e., 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 or storage at the pharmacy, 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 prior to drug dispensing. 
If the PQC is combined 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 8.4.7 (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 


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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. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Patients will be assigned to one of the two treatment arms (Section 4.1) in a ratio of 1:1. 
Randomization will be stratified by the presence of previous LG NMIBC episodes within 1 year 
of the current diagnosis at the initial Screening Visit (yes versus no). 
All patients will be centrally assigned to randomized study intervention using Interactive 
Response Technology (IRT). Before the study is initiated, the telephone number and call-in 
directions and/or the log in information and directions for the IRT will be provided to each site. 
This is an open-label study; potential bias will be reduced by the central randomization. At 
randomization, once the patient is confirmed to be eligible, the Investigator or suitably trained 
delegate will: 
1. Define two treatments to each patient and explain that the patient would receive one of 
the two treatments once randomized. This needs to be explained prior to randomization. 
The information will be recorded in the IRT system. 
2. Obtain a unique randomization number via the IRT. The system will randomize the 
eligible patient to one of the two treatment arms. The stratification information of the 
patient must be obtained from the Investigator by the IRT prior to randomization. 
If the patient is ineligible and not randomized, the IRT should be contacted to terminate the 
patient in the system. Once assigned, the randomization number must not be reused for any other 
patient and the randomization for that individual must not be changed, even if the patient is 
re-screened.  
If a patient withdraws from participation in the study, then his or her enrollment/randomization 
code cannot be reused. Withdrawn patients will not be replaced. 
The treatment given to patients will be determined by the randomization scheme in the IRT. The 
randomization scheme will be produced by a computer software program that incorporates a 
standard procedure for generating randomization numbers. One randomization list, using block 
randomization method will be generated, and all centers will use the same list in order to 
minimize any imbalance in the number of patients assigned to each treatment arm. 
Although BL006 is an open-label study, access to treatment information by UroGen personnel 
will be restricted and will be by role basis to maintain the integrity of the study. An independent 
statistical group (external to Sponsor), not involved in the study conduct, will prepare data 
reports for the Data Review Committee (DRC) for this open-label study. Details will be 
presented in the DRC Charter and in the Trial Integrity Plan. 
6.4. 
Study Intervention Compliance 
The study treatment will be administered at specified treatment visits by properly trained study 
site staff members. Each drug administration (including date, time, volume administered) will be 
documented in the patient’s file and eCRF. 


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6.5. 
Dose Modification 
Not applicable. 
6.5.1. 
Retreatment Criteria 
Not applicable. 
6.6. 
Continued Access to Study Intervention after the End of the Study 
No study interventions will be administered to patients after the patient has exited from the study. 
6.7. 
Treatment of Overdose 
Not applicable. 
6.8. 
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 
(e.g., medical or surgical interventions) related to urothelial cancer 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. 
NOTE: In patients undergoing protocol-specified TURBT, pre- or post-operative non-study 
chemotherapy is not permitted. 
In cases of symptomatic UTI, the patient will be treated with a full 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 Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.8.1. 
Rescue Medicine 
Not applicable. 


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7. 
Discontinuation of Study Treatment and Patient 
Discontinuation/Withdrawal 
7.1. 
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. 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. 
Patients considered NCR in either study arm at the 3-Month Visit (Visit 3) will be treated with 
TURBT. Note: If the Investigator determines that a formal TURBT in the operating room is 
unnecessary following cystoscopy and biopsy of remaining lesions (e.g., residual disease can be 
addressed by in office biopsy and/or fulguration), such an alternative procedure is permitted 
based on the Investigator’s medical judgment. Patients who are either CR or NCR at the 3-Month 
(Visit 3) in either study arm who have a recurrence of LG NMIBC or disease progression in the 
Follow-up Period will undergo EOS assessments at the EOS Visit and exit the study and will be 
treated according to best practice (i.e., SoC) by their treating physician. 
If a patient discontinues study treatment during the treatment period or at any time prior to the 
3-Month Visit, the patient, unless otherwise indicated, should remain in the study and all relevant 
visits and procedures should continue per protocol. 
7.1.1. 
Temporary Withholding of Study Treatment 
If at any time the Investigator identifies myelosuppression, evidence of active UTI, or other 
significant clinical event or laboratory derangements during the study defined by the parameters 
below, treatment may be postponed for up to 4 weeks until clinical event resolves and/or 
laboratory values improve (See Section 8.3.3.1): 
• Absolute neutrophil count ≤ 1,000/μL (≥ 1.0×109/L), 
• Platelets ≤ 80,000/μL (≤ 80×109/L) 
• AST (SGOT)/ALT (SGPT) ≥ 5 × ULN 
• Lab evidence of active UTI 
7.1.2. 
Rechallenge 
No change in dose will be performed for patients who re-initiate their study intervention after 
temporary withholding (See Section 7.1.1).  


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7.2. 
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.  
The Investigator may withdraw a patient from the study for the following reasons: 
• Pregnancy 
• Significant study non-compliance such that the Investigator believes that it is in the best 
interests of the study and/or the patient to withdraw the patient from the study 
• If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the patient 
• Patient is lost to follow-up (see Section 7.3) 
The reason for patient discontinuation or withdrawal from the study will be recorded on the eCRF.  
At the time of discontinuing from the study, an EOS Visit should be conducted, as shown in the 
SoA. See SoA for data to be collected at the time of study discontinuation and for any further 
evaluations that need to be completed. The patient will be permanently discontinued both from 
the study intervention and from the study at that time. 
7.3. 
Lost to Follow-up 
A patient will be considered lost to follow-up if he or she fails to return for 2 sequential 
scheduled visits and is unable to be contacted by the study 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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8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA. Protocol waivers or exemptions 
are not allowed. 
Adherence to the study design requirements, including those specified in the SoA, 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 (e.g., 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. 
8.1. 
Study Assessments and Procedures by Visit 
8.1.1. 
Screening And Randomization Period (Day -28 to Day 0 or Day -14 to Day 0) 
Note: For patients that need a biopsy, the screening period is up to 28 days. For patients that do 
not need a biopsy, the screening period is up to 14 days. Randomization should occur after 
screening evaluations are completed and it is confirmed that the patient qualifies for the study. 
Every effort should be made to minimize the time interval between diagnosis and treatment. 
Screening procedures are to provide evidence of low grade NMIBC and no evidence of high 
grade disease.  
8.1.1.1. 
Screening Visit (Day -28 to Day 0 or Day -14 to Day 0) 
The following procedures will be performed at Screening (Visit 1): 
All patients: 
• Obtain written informed consent before any study-related procedures are performed 
• Inclusion and exclusion criteria 
• Demographics 
• Administer QLQ-NMIBC24 questionnaire (for baseline score) 
• Medical/Surgical and Smoking history 
• Concomitant medication review 
• Past therapy including any medical or surgical interventions related to urothelial cancer 
• Full physical examination (including height and weight) and urology-oriented physical 
examination 
• Vital signs (blood pressure, pulse rate, respiration rate, and body temperature) 
• Clinical laboratory tests (serum chemistry and hematology) (at central laboratory) 


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• Urinalysis (dipstick on-site). If positive for infection, add culture and sensitivity at 
Screening (at local laboratory). 
• Urine or serum pregnancy test (if appropriate) (at local laboratory) 
• 
Cystoscopy and voiding urine cytology (at central pathology) (if not performed within 
6 weeks of initial Screening Visit) 
• Collection of a single representative cold cup biopsy, if no histologic confirmation of LG 
tumor within 8 weeks of initial Screening Visit (send to central pathology). Note: This is 
a diagnostic biopsy to demonstrate histopathology of tumor and resection of tumor is not 
to be performed. 
• Computerized tomography (CT) Urogram, retrograde pyelogram, or magnetic resonance 
imaging (MRI) (if other tests are contraindicated) to rule out UTUC (acceptable if 
performed within 6 months of initial Screening Visit) 
• AE review 
8.1.1.2. 
Randomization (Day 0) 
The following procedures will be performed at Day 0: 
All patients: 
• Perform randomization 
• Schedule TURBT or first UGN-102 instillation 
8.1.2. 
Treatment Period: Visits 2a to 2f (Day 1 to 36 / Week 1 to 6) for UGN-102 ± 
TURBT Patients or Visit 2 (Day 1 / Week 1) for TURBT Alone Patients 
Note: Windows are provided to accommodate patient logistics in scheduling. The window for 
Visit 2a (Day 1 / Week 1) for UGN-102 ± TURBT patients or Visit 2 (Day 1 / Week 1) for TURBT 
Alone patients is Day 0 +0/+28 days (i.e., within 28 days after randomization). Thus, Day 1 does 
not necessarily need to be the day after Day 0, e.g., in the event additional time is required to 
initiate treatment due to logistics such as scheduling procedure or training for UGN-102 
instillation. Every effort should be made to minimize the time interval between diagnosis and 
treatment. The window for Visits 2b to 2f (Day 8 to 36 / Week 2 to 6) for UGN-102 ± TURBT 
patients is -1/+3 days. Instillations for UGN-102 ± TURBT patients should not occur more 
frequently than 6 days apart. 
The following procedures will be performed at Visit 2 (Day 1) through Visit 2f (Day 36) for 
UGN-102 patients and at Visit 2 (Day 1) for TURBT Alone patients: 
All patients: 
• Administer QLQ-NMIBC24 questionnaire  
• Concomitant medication review 
• Urology-oriented physical examination 
• Vital signs (blood pressure, pulse rate, respiration rate, and body temperature) 


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• Clinical laboratory tests (serum chemistry and hematology) (at central laboratory) 
• Urinalysis (dipstick on-site) 
• AE review 
UGN-102 (± TURBT) patients: 
• Administer study treatment* 
• Keep patient in clinic for 30 to 60 minutes post instillation 
• Urine or serum pregnancy test (At Visit 2a only) (if appropriate) (at local laboratory) 
TURBT Alone patients: 
• Perform TURBT 
• Urine or serum or pregnancy test (At Visit 2 only) (if appropriate) (at local laboratory) 
* The PI or sub-Investigator must perform the first instillation on the first patient at his/her site. 
Thereafter, an appropriately trained and delegated site staff member (as per site standard 
practice for instillations) may perform subsequent instillations, provided an appropriately 
trained study physician is on site during the procedure. 
8.1.3. 
Waiting Period: Week 7 to 13 (UGN-102 ± TURBT) or Week 2 to 13 (TURBT 
Alone)  
Patients will enter a Waiting Period after receiving their last dose of study intervention in the 
Treatment Period. The Waiting Period will extend up to the Visit 3 Disease Assessment Visit 
(i.e., for assessment of response) (Visit 3, Month 3). 
8.1.4. 
Monthly Telephone Contact Visits: Months 2, 4, and 5 ± 1 week (UGN-102 ± 
TURBT) or Months 1, 2, 4, and 5 ± 1 week (TURBT Alone) 
Patients will be contacted by phone at Month 1 (TURBT Alone patients) and Months 2, 4, 5 (all 
patients) in the first year Follow-up Period to check for the following: 
• Concomitant medication review 
• AE review 
8.1.5. 
Disease Assessment Visit: Visit 3 (Month 3 ± 1 week) 
The following procedures will be performed at Visit 3 (Month 3) (for determination of response 
to treatment): 
All patients: 
• Administer QLQ-NMIBC24 questionnaire  
• Concomitant medication review 
• Body weight 
• Vital signs (blood pressure, pulse rate, respiration rate, and body temperature) 


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• Clinical laboratory tests (serum chemistry and hematology) (at central laboratory) 
• Urinalysis (dipstick on-site) 
• Cystoscopy and voiding urine cytology (at central pathology) for evaluation of durability 
response (Sections 8.2.1 and 8.2.2) 
• Biopsy remaining lesions (if indicated; Sections 8.2.1 and 8.2.2) (send to central 
pathology) 
• AE review 
The following assessments apply only to NCR patients at Visit 3 (Month 3). 
• Urine or serum pregnancy test (if appropriate) (at local laboratory) 
• Schedule TURBT as soon as possible (Every attempt should be made to perform TURBT 
within 1 month of this visit) 
• Perform TURBT (Note: If the Investigator determines that a formal TURBT in the 
operating room is unnecessary following cystoscopy and biopsy of remaining lesions 
(e.g., residual disease can be addressed by in office biopsy and/or fulguration), such an 
alternative procedure is permitted based on the Investigator’s medical judgment.) 
8.1.6. 
Follow-up Period including EOS Visit: Visit 4, 5, 6, 7, 8, 9, 10 (Months 6, 9, 12, 
15, 18, 21, 24 (EOS) ± 2 weeks) 
Follow-up visits start at Month 6 and continue every 3 months thereafter until completion 
of all the patient’s follow-up visits at the EOS Visit (Visit 10, Month 24) or until 
recurrence/progression/death is documented, whichever comes first. 
Note: For those patients in the follow-up period who have a disease recurrence or progression, 
the EOS Visit needs to be completed. 
The following procedures will be performed at Follow-Up Visits including the EOS Visit 
(Visit 10, Month 24): 
All patients: 
• Administer QLQ-NMIBC24 questionnaire  
• Concomitant medication review 
• Vital signs (blood pressure, pulse rate, respiration rate, and body temperature) 
• Clinical laboratory tests (serum chemistry and hematology) (at central laboratory) (at 
Visit 4, Month 6 only) 
• Urinalysis (dipstick on-site) 
• Cystoscopy and voiding urine cytology (at central pathology) for evaluation of durability 
response (see Section 8.2.4) 


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• Biopsy of remaining lesions (if indicated; Sections 8.2.1 and 8.2.2) (send to central 
pathology) 
• AE review 
8.1.7. 
Unscheduled Visits 
When required, based on patient needs relating to the study or due to unforeseen circumstances, 
unscheduled visits can occur outside the scheduled window. The following procedures are 
recommended during these unscheduled visits, subject to the Investigator’s judgment: 
The following procedures will be performed at Unscheduled Visits: 
All patients: 
• Administer QLQ-NMIBC24 questionnaire  
• Concomitant medication review 
• Vital signs (blood pressure, pulse rate, respiration rate, and body temperature) 
• Urinalysis (dipstick on-site) 
• Cystoscopy and voiding urine cytology (at central pathology) for evaluation of durability 
response (see Section 8.2.4) 
• Biopsy of remaining lesions (if indicated; Sections 8.2.1 and 8.2.2) (send to central 
pathology) 
• AE review 
8.2. 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3 and 
Section 1.4). 
8.2.1. 
Measurements for Evaluation of Response at 3-Month Visit and Follow-up Visits 
Assessment of response will be based on the following: 
• Visual observation (white light cystoscopy) 
• Histopathology of any remaining/new lesions by central pathology lab, if applicable 
(NCR or suspected tissue) 
• Voiding urine cytology by central pathology lab 


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8.2.2. 
Evaluation of Response at 3-Month Visit and Follow-up Visits (Disease 
Assessment) 
Patient response will be determined at the 3-month Visit and every 3 months thereafter according 
to the following criteria. For more details, refer to Appendix 1 (Guidance on Evaluation of 
Response).  
• CR: A patient will be considered to have had CR if there is NDD in the 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 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 (3-month 
Visit) or recurrence (Follow-up Visits). 
• NCR: A patient will be considered to have had NCR if there is evidence of the 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 (PUNLMP) are not considered cancer and in such cases the 
patient would be considered CR. 
• Recurrence: Recurrence will be assessed every 3 months at Follow-up Visits 4, 5, 6, 7, 
8, 9, and 10 (until the end of participation in the study defined as until completion of all 
follow-up visits or until recurrence/progression/death is documented) for all patients. The 
criteria for determining recurrence is similar to that of NCR. 
• If evidence of disease is identified, patients will be staged according to the Tumor-
Node-Metastases (TNM) classification and graded according to the 2004 World Health 
Organization (WHO) classification of tumors. Any noted progression of tumor in terms 
of transition to high grade (central lab), muscle invasion (central lab), or distant disease 
(local assessment) will be documented by the site in the eCRF, and the patient will be 
considered to have completed the study at that time (see Section 8.2.3). 
• 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 or malignancy in general, 
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 (RBB) 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). 


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3. If histopathology is negative, the patient should be classified as having CR; if positive 
for cancer, the patient should be classified as NCR (3-month Visit) or recurrence 
(Follow-up Visits). 
• Indeterminate: A patient response will be indeterminate if the criteria for determining 
either CR or NCR/Recurrence is not fulfilled due to incomplete or missed assessment. 
Questionable interpretations must be resolved and not be assessed as indeterminate. 
Please note that a decision for the need of TURBT must be made at the 3-month Visit 
assessment. In case the evaluation of response is ‘indeterminate’ at this visit, sites must 
perform the required procedures as soon as possible in order to have an adequate 
response evaluation. 
8.2.3. 
Assessment of Tumor Progression 
The overall risk of progression for patients with LG papillary NMIBC at intermediate risk of 
recurrence ranges from 1 to 5% at 1 and 5 years (Babjuk, 2019). 
Diagnosis of bladder cancer at the 3-Month Visit or subsequent follow-up visits with an increase 
in stage or grade compared to baseline will be recorded in the evaluation of response, and the 
overall incidence will be compared with that reported in the literature. The patient will be 
considered to have completed the study at that time and will be treated according to best practice 
(i.e., SoC) by their treating physician. 
8.2.4. 
Assessment of Tumor Recurrence 
Follow-up will be conducted in patients who were defined as having CR or NCR (after 
undergoing TURBT) at the 3 Month Visit. 
Starting with the first follow-up visit (Study Visit 4, Month 6) and continuing at Visits 5, 6, 7, 8, 
9, and 10 (Months 9, 12, 15, 18, 21, and 24, respectively), information regarding disease status 
based on cystoscopy, cytology, and biopsy (when applicable) should be recorded. If a patient is 
defined as having recurrence, complete documentation should be obtained. If a patient has a 
positive urine cytology and/or a positive biopsy for cancer, they are considered as having 
urothelial cell cancer recurrence. If urine cytology is consistent with LG NMIBC but the biopsy 
is negative, the patient should be evaluated for the presence of UTUC. If the patient is positive 
for UTUC that was not present at baseline and there is no evidence of tumor within the bladder, 
this is considered new disease and the patient remains a CR for their LG NMIBC. If the patient is 
negative for UTUC, the urine cytology should be repeated. If the repeat urine cytology is 
consistent with urothelial cancer, the patient should be classified as recurrence. 
8.2.5. 
Pathological Evaluation 
Biopsies and urine cytology specimens obtained at screening or any other visit should be 
evaluated by the central laboratory (pathologist). Pathology reports from the central laboratory 
will be provided to Investigators. 


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8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
8.3.1. 
Physical Examinations 
At the visits specified in Section 1.2 and Section 1.3, a full physical examination or urology-
oriented physical examination will be performed. The patient’s physical condition will be 
examined and documented. This includes examination of main body systems, with focus on the 
urinary system. The examinations to be performed are summarized in Table 3. 
Table 3: 
Physical Examinations 
General Physical Examination will be 
performed at Screening Visit 1 (both 
treatment arms) 
Urology-Oriented Physical Examination will be 
performed Screening Visit 1* and the Treatment 
Period (Study Visits 2a-2f for UGN-102 ± 
TURBT or Visit 2 for TURBT Alone) (both 
treatment arms) 
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 (for male and female 
patients) (Screening visit only) 
Bimanual examination (female patients – 
Screening visit only) 
* Performed prior to cystoscopy at Screening. 
8.3.2. 
Vital Signs 
At each visit, the following vital signs measurements are to be taken: 
• 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. 
8.3.3. 
Clinical Safety Laboratory Assessments 
Samples for hematology and serum chemistry assessments will be taken according to the SoA in 
Section 1.3 and Section 1.4 and tested at the central laboratory. The assessments to be performed 
are listed in Table 4. Additional tests may be part of a clinical site’s local laboratory’s standard 
panel and therefore reported along with these specified tests. 


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8.3.3.1. 
Other significant laboratory derangements 
If at any time the Investigator identifies myelosuppression, evidence of active UTI, or other 
significant clinical event or laboratory derangements during the study defined by the parameters 
below, treatment may be postponed for up to 4 weeks until 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 (SGOT)/ALT (SGPT) ≥ 5 × upper limit of normal (ULN) 
• Lab evidence of active UTI 
The following table describes laboratory assessments to be performed in this study (Table 4): 
Table 4: 
Laboratory Safety Assessments* 
Liver Function Tests: 
SGOT/AST 
SGPT/ALT 
GGT 
Alkaline phosphatase 
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 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; EDC = electronic data 
capture; eGFR = estimated glomerular filtration rate; GGT = gamma-glutamyltransferase; SGOT = serum glutamic oxaloacetic 
transaminase; SGPT = serum glutamic pyruvic transaminase. 
* Laboratory samples will be kept per storage requirements as stated in the lab manual until shipped to central laboratory for 
analysis. 
 
Refer to the SoA (Section 1.3 and Section 1.4) for the timing and frequency of clinical 
laboratory tests. 
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 (e.g., in case of either temporary discontinuation) or within 4 weeks after the last 
administered dose of study intervention (i.e., 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. 


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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 and Section 1.4). 
A central laboratory will be used in this study, except for the pregnancy test (either urine or 
serum) and urinalysis which are performed at site or locally. 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 (e.g., 
AE), then the results must be recorded. 
8.3.4. 
Urinalysis 
At the visits specified in Section 1.3 and Section 1.4, samples will be taken for urinalysis, 
including culture and sensitivity (if indicative of infection) at the Screening Visit, and when 
otherwise clinically indicated. 
8.3.5. 
Pregnancy Testing 
A urine or serum pregnancy test will be conducted in female patients of childbearing potential at 
the Screening Visit, Visit 1, and Visit 2a (UGN-102 ± TURBT Patients) or Visit 2 (TURBT 
alone patients). A urine or serum pregnancy test is also performed at Visit 3 for NCR patients in 
both treatment arms. 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 prior to study treatment 
administration. 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Safety Reporting 
The definitions of AEs and SAEs can be found in Section 8.4.2. All AEs and SAEs will be 
collected from the signing of the ICF (Section 8.4.3). 
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 Section 8.4.3 and remain responsible for following up all 
applicable AEs including those that are serious, considered related to the study intervention or 
study procedures, or that caused the patient to discontinue the study treatment or from 
participation in the study (see Section 7). 
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 8.4.2, 
Section 8.4.6, and Section 8.4.7. 


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8.4.1. 
Safety and Other Assessments 
8.4.1.1. 
Safety Assessment Overview 
The safety of the 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 (PCS) 
• Clinically meaningful changes in physical examination findings including vital signs 
8.4.1.2. 
Quality of Life Assessment EORTC QLQ – NMIBC24  
The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life 
Questionnaire for NMIBC (QLQ-NMIBC24) is a 24-item validated, evidence-driven survey that 
assesses Health Related Quality of Life (HRQoL) for patients with intermediate to high risk 
NMIBC. It is designed to be administered at Visit 1, Visit 2a-2f (UGN-102 ± TURBT) or Visit 2 
(TURBT Alone), at 3, 6, 9, 12, 15, 18, 21, and 24-monthly intervals, and at Unscheduled Visits. 
The NMIBC24 is the only instrument exclusively designed to compare HRQoL between non-
muscle-invasive treatment modalities. Refer to Appendix 2. 
8.4.2. 
Adverse Events and Serious Adverse Events 
8.4.2.1. 
Definition of Adverse Events 
An AE means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 Code of Federal Regulations [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, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the Investigator (i.e., 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 intervention 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 
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• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention 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 (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
• 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. 
8.4.2.2. 
Definition of Serious Adverse Events  
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. 


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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 (e.g., sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
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. 
8.4.2.3. 
Classification of an Adverse Event 
8.4.2.3.1. 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 (e.g., 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 


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4 Life-threatening consequences: urgent intervention indicated (SAE) 
5 Death related to AE (SAE) 
8.4.2.3.2. 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 intervention 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. 
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. 
8.4.2.3.3. 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. 
8.4.3. 
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. 
All AEs (including local and systemic reactions not meeting the criteria for SAEs) and SAEs will 
be collected from the signing of the ICF until the Month-6 visit (Visit 4). Subsequent to the 
Month-6 visit, all SAEs (regardless of causality) and non-serious AEs assessed as related to 


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study treatments (UGN-102 or TURBT) or study procedures should be collected until the EOS 
Visit at the time points specified in the SoA (Section 1.3 and Section 1.4). Information will be 
captured on the appropriate eCRF including event description, time 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 time 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 or phone calls per the SoA (Section 1.3 and Section 1.4), the Investigator should 
inquire about the occurrence of AE/SAEs since the last visit/phone call. 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 be recorded. 
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 intervention or study participation, the Investigator must promptly 
notify the Sponsor within 24 hours. 
8.4.4. 
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. 
8.4.5. 
Follow-up of AEs and SAEs 
After the initial collected AE/SAE report, the Investigator 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 7.3). 
Further information on follow-up procedures is provided in Section 8.4.7. 
8.4.6. 
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 
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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 
intervention 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 intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/Independent Ethics Committee (IEC), and Investigators. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it 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. 
8.4.7. 
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 (IND) 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. 


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8.4.7.1. 
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 collection 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): 
 
Study Medical Monitor 
, MD, UroGen Pharma 
8.4.8. 
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 (see Section 8.4.6). 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 (e.g., 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 intervention 
by the Investigator will be reported to the Sponsor as described in Section 8.4.6. 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. 


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8.4.9. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.4.10. 
Adverse Events of Special Interest 
In this study, AESIs will be reviewed by the Sponsor on an ongoing basis. There are no 
requirements for the Investigator to make determination of AESIs and Investigators are to report 
AEs (including AESIs) in a consistent manner as described in Section 8.4.3.The list of AESIs is 
based on the most current safety profile of UGN-102 within the overall clinical development 
program. 
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) 
8.5. 
Pharmacokinetics 
Pharmacokinetic and pharmacodynamic parameters are not evaluated in this study. 
8.6. 
Genetics and/or Pharmacogenomics 
Genetics are not evaluated in this study. 
8.7. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.8. 
Immunogenicity Assessments 
Not applicable. 
8.9. 
Health Economics/Medical Resource Utilization and Health 
Economics 
The following health economics or medical resource utilization and health economics parameters 
may be exploratively summarized in this study (at analysis level): 
• Number of patients hospitalized for non-elective reasons, total number and length of 
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9. 
Statistical 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. All time-to-event 
variables (e.g., DFS, DOR, TTR) will be analyzed using Kaplan-Meier method. 
9.1. 
Statistical Hypotheses 
UroGen Pharma Ltd. (Sponsor) closed enrollment in Study BL006 on 10 Nov 2021 in order to 
pursue an alternative development strategy for UGN-102 in patients with LG IR NMIBC. 
Although patients who are already randomized are permitted to continue their study participation 
until the EOS, the study is not powered to perform any hypothesis testing. Therefore, all analyses 
will be descriptive in nature. 
9.2. 
Sample Size Determination 
The enrollment of this study has been stopped prematurely by the Sponsor in order to pursue an 
alternative development strategy for UGN-102 in the same patient population; 282 eligible 
patients who were screened on or before 10 Nov 2021 were randomized in this study. 
9.3. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Intent-to-Treat 
(ITT) 
The Intent-to-Treat (ITT) set includes all randomized patients who received any dose 
of UGN-102 (treatment arm) or at least one TURBT intervention (control arm). 
According to the ITT principle, patients will be analyzed according to the treatment 
and strata they have been assigned during randomization. The ITT will be the primary 
population for all efficacy analysis.  
Full Analysis Set 
(FAS) 
The Full Analysis Set (FAS) comprises all randomized patients. Patients will be 
analyzed according to the treatment and strata they have been assigned to during the 
randomization procedure. Sensitivity analyses of the efficacy endpoints may be 
performed using data from FAS if the FAS and ITT differ. 
Safety Set 
The Safety Set includes all patients who received any dose of UGN-102 (treatment 
arm) or at least one TURBT intervention (control arm). Patients will be analyzed 
according to the study treatment they actually received. All safety analyses will be 
conducted using the safety population. 
Per Protocol Set 
(PPS) 
The Per Protocol set (PPS) will include the subset of the patients in the ITT without 
major protocol deviations that would confound efficacy evaluation. All protocol 
deviations or conditions leading to exclusion from the PPS will be detailed in the 
protocol deviation plan and SAP. Sensitivity analyses of the primary endpoint of DFS 
may be performed using data from PPS if the PPS and ITT differ sufficiently. 


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As described in Section 4.1, patients considered NCR at the 3-Month Visit may receive an 
alternative procedure (e.g., biopsy and/or fulguration) if a formal TURBT is unnecessary based 
on the Investigator’s medical judgment. All NCR patients at the 3-Month Visit, irrespective of 
their mode of treatment, will be included in the analysis. 
9.4. 
Statistical Analyses 
The SAP will include a more detailed description of the statistical analyses described in this 
section.  
9.4.1. 
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% confidence interval (CI) for 
proportions using the exact approach. For continuous variables, summary tables will be provided 
giving sample size, arithmetic mean, standard deviation (SD), coefficient of variation (if 
appropriate), median, minimum and maximum, percentiles, and 95% CI for means of variables. 
Multiplicity 
Since no formal hypothesis will be tested, there will be no adjustment for multiplicity. All 
endpoints will be analyzed and interpreted descriptively. 
9.4.2. 
Primary Endpoint(s) 
The primary efficacy endpoint DFS is defined as the time from randomization until the earliest 
date of failure to be rendered free of local disease at the 3-Month assessment after the TURBT 
procedure, recurrence of low-grade disease after the 3-Month assessment (i.e., during the 
follow-up period), progression to high-grade disease, or death due to any cause. 
NCR at the 3-Month disease assessment in the UGN-102 ± TURBT treatment arm is not 
considered as a DFS event because treatment failure is not an event in a neoadjuvant setting. 
However, NCR (i.e., residual disease) at the 3-month disease assessment after the TURBT 
procedure (i.e., in the TURBT arm) will be considered as a DFS event. Progression to HG 
disease any time during the study (even at the 3-month disease assessment) will be considered as 
a DFS event in either arm.  
DFS will be analyzed based on the data observed in the ITT population, according to the 
treatment arm patients were randomized and the strata they were assigned at randomization. The 
distribution of DFS will be estimated using the Kaplan-Meier method. The median DFS along 
with 95% CIs will be presented by treatment arm. 
A stratified Cox regression model will be used to estimate the HR of DFS, along with 95% CIs 
(using the same strata information as above). No p-value will be generated. 
The ITT set that includes all randomized patients who received any dose of UGN-102 (treatment 
arm) or at least one TURBT intervention (control arm), will serve as the primary population for 
the analyses of efficacy data in this study. 


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Handling of Missing Values/Censoring/Discontinuations  
If a patient has not had an event, DFS will be censored at the date of the last adequate disease 
assessment (i.e., a visit when all scheduled disease assessments have been done).  
DFS will be censored if no DFS event is observed before the data cut-off date of analysis or the 
date when a new anti-cancer therapy or another investigational treatment for cancer is started, 
whichever occurs earlier. The censoring date will be the date of last adequate disease assessment 
before either of these two dates. Further details of censoring rules will be provided in the SAP. 
Supportive Analyses 
The primary analysis for DFS may be repeated with data based on FAS and PPS if the FAS/PPS 
and ITT differ sufficiently. 
Subgroup Analysis 
Subgroup analyses will be performed on each level of the following factors using ITT 
population. 
Subgroups will include (but not limited to): 
• Age group (<65, 65 to <75, ≥75 years),  
• BMI category (<30 kg/m2, ≥30 kg/m2),  
• Sex (male, female)  
• Tumor size (>3 cm, ≤3 cm) 
• Tumor (single, multiple) 
• Recurrence within 1 year of current diagnosis (0 vs ≥1). 
9.4.3. 
Secondary Endpoint(s) 
The secondary efficacy endpoints are described below. All analyses will be evaluated in ITT set 
without formal comparison. Sensitivity analyses may be performed using data from FAS if the 
FAS and ITT differ. 
Time to recurrence (TTR) 
Time to recurrence (TTR) is defined as the time from randomization until the earliest date of 
recurrence of low-grade disease or progression to high-grade disease. The distribution function 
of TTR will be estimated using the Kaplan-Meier method. The median TTR along with 95% CIs 
will be presented by treatment arm. 
Complete Response Rate (CRR) at 3-Month Disease Assessment 
Complete response rate (CRR), defined as the proportion of patients who achieved CR at the 
3-Month disease assessment. The responses at 3-Month will test the CRR defined as percentage 
of patients with CR at the 3-Month visit. CRR will be presented by treatment arm along with 
approximate 95% CIs. 
Duration of Response (DOR) 
Duration of response (DOR), defined as the time from first documented CR until the earliest date 
of recurrence of low-grade disease, progression to high-grade disease, or death due to any cause. 
DOR applies only to patients who achieved CR at the 3-Month disease assessment. The 


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distribution function of DOR will be estimated using the Kaplan-Meier method. The median 
DOR along with 95% CIs will be presented by treatment arm. 
Observed CRR at Scheduled Disease Assessment Timepoint 
Observed CRR at scheduled disease assessment timepoints, defined as the proportion of patients 
who had CR at the 3-Month disease assessment and maintained CR up to that particular follow-
up disease assessment. CRR will be presented with nominal 95% exact CI (Clopper-Pearson) for 
each treatment arm at each scheduled timepoint. 
Incidence of TURBT  
Proportion of patients requiring TURBT in each arm and average number of TURBT 
intervention per patient in each arm will be summarized. 
Changes from Baseline in HRQoL 
The EORTC QLQ-NMIBC24 questionnaire will be used to assess patients’ satisfaction with 
their treatment. The EORTC QLQ-NMIBC24 is a self-reported 24-item NMIBC specific 
instrument that assesses 11 domains: 2 functional scales or single item (sexual function, sexual 
enjoyment), and 9 symptom scales or single items (urinary symptoms, malaise, future worries, 
bloating and flatulence, male sexual problems, intravesical treatment issues, sexual intimacy, risk 
of contaminating partner, and female sexual problems).  
A mixed effect model for repeated measures (MMRM) will be performed to evaluate the two 
treatment arms with respect to changes in the QLQ-NMIBC24 measures. Scoring of raw Quality 
of Life (QoL) and methods for handling of missing items or missing assessments will be handled 
according to the scoring manual. No imputation will be applied if the total or subscale scores are 
missing at a visit, since all available data during the study will be used in the MMRM analysis 
which assume that the missing scores at any time point are missing-at-random. Additional 
sensitivity analysis may be performed to assess the possible violation of missing-at-random 
assumption for the missing data mechanism if deemed appropriate. Details will be specified in 
the SAP.  
Descriptive statistics will be used to summarize the scored scales at each scheduled assessment 
time point for each of the domains. Additionally, change from baseline in the domain scores at 
the time of each assessment will be summarized. Patients with an evaluable baseline score and at 
least one evaluable post baseline score during the treatment period will be included in the change 
from baseline analyses. 
No formal statistical test will be performed and hence no multiplicity adjustment will be applied. 
The ITT will be used for analyzing QoL data. 
9.4.4. 
Exploratory Endpoints 
Number of patients hospitalized for non-elective reasons, total number and length of non-elective 
hospitalizations will be explored and summarized by treatment arm in this study. Additional 
exploratory endpoints may be added in the SAP. 


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9.4.5. 
Safety Analysis 
Safety analyses will be conducted for the safety set. The assessment of safety will be based 
mainly on the frequency of AEs and on the number of laboratory values that fall outside of 
pre-determined ranges. Other safety data (e.g., physical examination, vital signs) will be 
considered as appropriate. All listings and tables will be presented by treatment arm. 
The overall observation period will be divided into three mutually exclusive segments: 
1. Pre-treatment period: from day of patient’s informed consent to the day before 
administration of first treatment  
2. On-treatment period: from day of first treatment administration to 30 days after last 
treatment administration 
3. Post-treatment period: starting at day 31 after last treatment. 
Adverse Events and Serious Adverse Events 
Summary tables for AEs will include only AEs that started or worsened during the study (i.e., 
on-treatment and post-treatment periods), the TEAEs. However, all safety data will be listed and 
those collected during the pre-treatment and post-treatment period are to be flagged. 
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 by treatment arm. 
Deaths reportable as SAEs and non-fatal SAEs will be listed by patient and tabulated by type of 
adverse event and treatment arm. 
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 SAP. 
Clinical Laboratory Tests 
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 (e.g., 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. 


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The following by-treatment summaries will be generated separately for hematology, 
biochemistry, and urinary laboratory tests as appropriate: 
• frequency table for newly occurring on-treatment grades 3 or 4 (see below for details) 
• shift tables using CTCAE grades to compare baseline to the worst on-treatment value 
• for laboratory tests where CTCAE grades are not defined, shift tables using the 
low/normal/high/(low and high) 
• classification to compare baseline to the worst on-treatment value. 
• listing of all or selected laboratory data with values flagged to show the corresponding 
CTCAE grades and the classifications relative to the laboratory normal ranges. 
In addition to the above-mentioned tables and listings, other exploratory analyses, for example 
figures plotting time course of raw or change in laboratory tests over time or box plots might be 
generated and will be specified in the SAP. 
Physical Examination 
Full physical examination will be performed at screening only. Urology oriented physical 
examination will be performed at screening and during treatment visits. Details are provided in 
Section 1.3, Section 1.4 and Section 8.3.1. 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 
The following analysis will be performed for vital signs: 
• shift table baseline to worst on-treatment result 
• table with descriptive statistics at baseline, one or several post-baseline time points and 
change from baseline to this/these post-baseline time points. 
Definitions of clinically notable abnormal results will be specified in the SAP. Patients 
exhibiting clinically notable vital sign abnormalities will be listed. 
9.4.6. 
Other Analysis 
Additional analyses may be performed and will be described in the SAP. 
9.5. 
Interim Analysis 
No interim analysis is planned for this study. Final analysis will be performed after all patients 
have completed the study. 
 


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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
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 (CIOMS) 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 (e.g., advertisements) must be submitted to an Institutional Review 
Board (IRB)/Independent Ethics Committee (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 Code of Federal Regulations (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 
10.1.2. 
Finance and Insurance 
10.1.2.1. Finance  
The study is financed by the Sponsor as detailed in the financial agreement between the Sponsor 
and the Investigator/institution. 


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10.1.2.2. Insurance 
The study will be covered in accordance with local requirements and per the clinical trial 
agreement (CTA).  
10.1.3. 
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 (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center. 
10.1.3.1. 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 rescreened are required to sign a new ICF. 
10.1.4. 
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. 


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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. 
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 study 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. 
10.1.5. 
Data Review Committee 
Since there is no interim analysis planned for this study, there will be no external data review 
committee (DRC). 
10.1.6. 
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. 
10.1.7. 
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. 
10.1.8. 
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 a study 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 


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the data entered into the electronic case report form (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 
with the investigational staff. 
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 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. 
10.1.9. 
Data Quality Assurance 
All patient data relating to the study will be recorded on electronic or paper CRF unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF. 
Guidance on completion of eCRFs will be provided in the CRF Completion Guidelines (CCGs). 
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 (i.e., data 
QC checks) will be implemented for the electronic data capture (EDC). Any missing data or data 
anomalies will be communicated to the sites for clarification/resolution. 
Monitoring details describing strategy methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical study is conducted, data are generated, and biological specimens are collected, 
documented (i.e., recorded), and reported in compliance with the protocol, ICH GCP, and 
applicable regulatory requirements (e.g., Good Laboratory Practices [GLP]).  
The Sponsor or designee is responsible for the data management of this study including quality 
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The Sponsor assumes accountability for actions delegated to other individuals (e.g., 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. 
10.1.10. 
Data Handling and Record Keeping 
10.1.10.1. 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 electronic data capture 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 at the site under the supervision of 
the site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 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. 
10.1.10.2. 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. 


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10.1.11. 
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 principal investigator (PI)/study staff is responsible for knowing and 
adhering to their IRB/IEC requirements. 
10.1.12. 
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. 
10.1.13. 
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 study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 


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Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
For study termination: 
• Discontinuation of further study intervention 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 
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 Food and Drug Administration (FDA). 
10.1.14. 
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. 


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10.1.15. 
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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Perry RR, Greaves BR, Rasberry U, Barranco SC. Effect of treatment duration and glutathione 
depletion on mitomycin C cytotoxicity in vitro. Cancer Res. 1992;52(17):4608-4612. 
Racioppi M, Volpe A, Cappa E, et al. Intensive intravesical mitomycin C therapy in non-muscle-
invasive bladder cancer: a dose intensity approach. Urol Int. 2010;85(3):266-269.  
Sadeghi HM, Seitz B, Hayashi S, LaBree L, McDonnell PJ. In vitro effects of mitomycin-C on 
human keratocytes. J Refract Surg. 1998;14(5):534-40. 
Schmittgen TD, Wientjes MG, Badalament RA, Au JL. Pharmacodynamics of mitomycin C in 
cultured human bladder tumors. Cancer Res. 1991;51(15):3849-56. 
Serretta V. Optimizing intravesical chemotherapy in patient with non muscle invasive bladder 
carcinoma. Arch Ital Urol Androl. 2008;80(4):143-148. 
Slee PH, de Bruijn EA, Leeflang P, Kuppen PJ, van den Berg L, van Oosterom AT. Variations in 
exposure to mitomycin C in an in vitro colony-forming assay. Br J Cancer. 1986;54(6):951-5. 
Walker MC, Masters JR, Parris CN, Hepburn PJ, English PJ. Intravesical chemotherapy: in vitro 
studies on the relationship between dose and cytotoxicity. Urol Res. 1986;14(3):137-40. 
Wientjes MG, Dalton JT, Badalament RA, Drago JR, Au JL. Bladder wall penetration of 
intravesical mitomycin C in dogs. Cancer Res. 1991;51(16):4347-4354. 


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Protocol BL006 version 2.0 
 
79 
Appendix 1. 
Guidance on Evaluation of Response 
Response will be evaluated based on visual evaluation by cystoscopy (white light), histopathology 
of any remaining/new lesions (by central pathology lab), and urine cytology (by central pathology 
lab) at the 3-month visit and every 3-months thereafter (i.e., months 6, 9, 12 etc.). 
CR (Complete Response): A patient will be considered to have CR if there is No Detectable 
Disease (NDD) in the bladder by cystoscopy, biopsy (if indicated) and urine cytology. 
NCR (Non-complete Response) at 3-Month disease assessment: There is evidence of disease 
under study. 
Recurrence (at follow-up visits): There is evidence of disease under study. Note: The criteria to 
define NCR and recurrence are the same. 
Indeterminate: The criteria for determining either CR or NCR/Recurrence is not fulfilled due to 
incomplete or missed assessment. Questionable interpretations must be resolved and not be 
assessed as indeterminate. Please note that a decision of the need for TURBT must be made at the 
3-month visit assessment. In case the evaluation of response is ‘indeterminate’ at this visit, sites 
must perform the required procedures as soon as possible to have an adequate response evaluation. 
All required procedures must be performed at efficacy assessment visits to determine the overall 
response of a patient. However, for clarity the response evaluation has been broken down by each 
procedure (1 & 2). Both are combined in Table 7 to determine the overall response of a patient. 
1. Evaluation Based on Cystoscopy and Biopsy/Histopathology 
a) If any lesion(s) appear endoscopically, even if they appear necrotic, the physician must 
biopsy the visible lesion(s). If the histopathology reveals malignancy, the patient’s 
response will be recorded as NCR/Recurrence. 
b) If visual assessment indicates no remaining lesions or histopathology reveals no malignancy 
of the remaining lesions, then it is determined as NDD (No Detectable Disease). 
c) If cystoscopy was not performed and/or the biopsy was not done when indicated, the 
evaluation will be indeterminate. 
Table 5: 
Evaluation Based on Cystoscopy and Biopsy/Histopathology 
Lesion Found 
by Cystoscopy? 
Biopsy Done? 
Histopathology 
Result 
Evaluation  
Yes 
Yes 
Malignant 
NCR/Recurrence 
Yes 
Yes 
No malignancy 
NDD 
No 
NA 
- 
NDD 
Yes 
No 
- 
Indeterminate 
Not done 
- 
- 
Indeterminate 
NA = not applicable; NCR = non-complete response; NDD = no detectable disease. 
 


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Figure 2. 
Evaluation Based on Cystoscopy and Biopsy/Histopathology 
 
2. Evaluation Based on Urine Cytology, Diagnosis of UTUC and Random Bladder 
Biopsies of the Bladder (if indicated) 
Urine Cytology Results 
Urine cytology specimens will be analyzed using Paris classification and can have the following 
main outcomes which will be collected in the eCRF: 
1. Atypical cells 
2. Negative for high grade urothelial carcinoma (HG UC) 
3. Other malignancies, primary and metastatic 
4. HG UC 
5. Low grade urothelial carcinoma (LG UC) 
6. Suspicious for HG UC 
7. Unsatisfactory specimen 
Evaluation of Response 
a) If the results are interpreted as 1, 2, or 3 above, then NDD is determined by cytology.  
b) If the cytology result indicates either HG UC (4) or LG UC (5) or is suspicious for 
HG UC (6) then the results should be correlated with the cystoscopy or biopsy findings. 
1. If there are no visible lesions on cystoscopy, or a biopsy reveals no evidence of 
LG NMIBC, the urine cytology must be repeated. 
2. If the repeat cytology result is either 1, 2, or 3, then NDD is determined by cytology. 
Cystoscopy
Biopsy/
Histopathology
NCR/Recurrence
Malignant
NDD
Indeterminate
Not
Done
Effacacy 
Assessment 
Visit
Lesion Found
Not Done
No Lesions Found
No Malignancy


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3. If the repeat cytology result remains 4, 5, or 6 the investigator must exclude urothelial 
carcinoma of the upper tract (UTUC) and occult carcinoma of the bladder or urethra.  
i. 
If UTUC is diagnosed, then NDD is determined by cytology.  
ii. 
If UTUC is not diagnosed, then the investigator must perform Random 
Bladder Biopsies (RBB). Biopsies will be carried out 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). 
1. If the histopathology of any of these biopsies reveals malignancy, 
patient’s response will be recorded as NCR/recurrence. 
2. If the histopathology reveals no malignancy, then it is determined as NDD. 
c) If either cytology, and/or required repeat cytology, and/or upper tract evaluation (as 
indicated), and/or RBB of the bladder (as indicated) is not performed, the evaluation 
will be indeterminate.  
d) If the cytology result is inconclusive due to unsatisfactory specimen, the sample must 
be retaken as soon as possible. The response will be determined following criteria a) 
through c). Evaluations based on an unsatisfactory specimen will be indeterminate. 
Table 6: 
Evaluation Based on Urine Cytology, Diagnosis of UTUC and 
Random Bladder Biopsies 
Cytology Results 
Repeat 
Cytology 
Required? * 
Repeat 
Cytology 
Results 
Evaluation 
to Exclude 
UTUC? 
UTUC 
Diagnosed? 
Evaluation 
1. Atypical cells or 
2. Negative for HG UC or 
3. Other malignancies, 
primary and metastatic 
NA 
- 
NA 
- 
NDD 
4. HG UC or 
5. LG UC or 
6. Suspicious for HG UC 
Yes 
1 or 2 or 3 
NA 
- 
NDD 
4 or 5 or 6 
Yes 
4 or 5 or 6 
Yes 
Yes 
NDD 
4 or 5 or 6 
Yes 
4 or 5 or 6 
Yes 
Not done 
Indeterminate 
4 or 5 or 6 
Yes 
Not done 
- 
- 
Indeterminate  
4 or 5 or 6 
Yes  
4 or 5 or 6 
Yes  
No ** 
Will be determined 
by the results of the 
biopsies. *** 
Not done 
- 
- 
- 
- 
Indeterminate 
HG = high grade; LG = low grade; NA = not applicable; NCR = non-complete response; 
NDD = no detectable disease; UC = urothelial carcinoma; UTUC = upper tract urothelial carcinoma. 
* 
Results should be correlated with the cystoscopy. If there is NDD by cystoscopy/biopsy, cytology 
must be repeated. 
** 
A Random Bladder Biopsy (RBB) must be performed in 6 bladder mucosal sites: bladder floor, 
right wall, left wall, dome, posterior wall, and prostatic urethra (in males) or bladder neck (in females). 
*** If the result indicates no malignancy then NDD will be determined, otherwise, if the result indicates 
malignancy, then evaluation of response will be recorded as NCR/Recurrence. 


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Protocol BL006 version 2.0 
 
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Figure 3. 
Evaluation Based on Urine Cytology, Diagnosis of UTUC and Random
 
Bladder Biopsy 
 
 
Cytology
Atypical/
Negative/
Other Malignancy
HG UC/
LG UC/
Suspicious HG UC
NDD
Repeat
Cytology*
Indeterminate
Not
Done
Effacacy 
Assessment 
Visit
UTUC
Evaluation
Not Done
Atypical/
Negative/
Other Malignancy
Not Done
HG UC/
LG UC/
Suspicious HG UC
UTUC Diagnosed
UTUC Not Diagnosed
NCR/Recurrence
Random
Bladder
Biopsy**
Indeterminate
NDD
No Malignancy
Malignancy
Not Done
** Random Bladder Biopsy (RBB) must 
be performed in 6 bladder mucosal sites: 
bladder floor, right wall, left wall, dome, 
posterior wall, and prostatic urethra 
(in males) or bladder neck (in females).  
* Results should be correlated 
with the cystoscopy. If there is 
NDD by cystoscopy/biopsy, 
cytology must be repeated. 


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Protocol BL006 version 2.0 
 
83 
3. Overall Response based on Cystoscopy, Biopsy/Histopathology, Cytology and Diagnosis 
of UTUC and Random Bladder Biopsies  
a) If there is evidence of UC by either of the methods (cystoscopy followed by biopsy/ 
histopathology or urine cytology), the patient will be recorded as NCR (3-Month Visit) or 
recurrence (follow-up visit), irrespective of the outcome of the other procedure, even if it 
was not done. 
b) Else if evaluation is indeterminate by either or both methods the Evaluation of Response 
is Indeterminate. 
c) Otherwise, the Evaluation of Response is CR. 
Table 7: 
Evaluation of Response Based on All Assessments 
Cystoscopy/Histopathology 
Cytology/UTUC Diagnosis/ 
Random Bladder Biopsies 
Evaluation of Response 
(to be entered in the CRF) 
NDD 
NDD 
CR 
NDD 
NCR/Recurrence 
NCR/Recurrence 
NDD 
Indeterminate* 
Indeterminate 
NCR/Recurrence 
NDD 
NCR/Recurrence 
NCR/Recurrence 
NCR/Recurrence 
NCR/Recurrence 
NCR/Recurrence 
Indeterminate 
NCR/Recurrence 
Indeterminate 
NDD 
Indeterminate 
Indeterminate 
NCR/Recurrence 
NCR/Recurrence 
Indeterminate 
Indeterminate 
Indeterminate 
CR = complete response; CRF = case report form; NCR = non-complete response; 
NDD = no detectable disease; UTUC = upper tract urothelial carcinoma. 
* 
These scenarios will be adjudicated on a case-by-case basis. 


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Protocol BL006 version 2.0 
 
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Appendix 2. 
EORTC QLQ – NMIBC24 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Please go on to the next page 


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Protocol BL006 version 2.0 
 
86 
Appendix 3. 
Protocol Revision History 
Version 
Date 
Description of Changes 
Brief Rationale 
1.1 
16 Sep 2020 • Removed Sponsor signature page 
 
 
 
 
• Revised the visit window for 
Visit 2a (UGN-102 patients) and 
Visit 2 (TURBT patients) in 
Sections 1.3, 1.4, and 8.1.2 
 
 
 
 
 
• Edited title and content of 
Sections 6.1.2 and 6.1.4 
 
 
 
 
• Corrected visit number in 
Section 8.1.5 
 
 
 
• Deleted sentence in Section 8.4.3 
 
 
2.0 
20 Dec 2021 • Updated key roles and contact 
information 
 
 
 
• Added notification of early 
study enrollment closure 
 
 
 
 
• Clarified that NCR patients at the 
3-month Visit may undergo an 
alternative procedure (e.g., biopsy 
and/or fulguration) to address 
residual disease if a formal TURBT 
is unnecessary based on the 
Investigator’s medical judgment 
 
 
 
 
• Revised statistical considerations to 
reflect that the study is not powered 
to perform hypothesis testing or 
statistical comparison, and that all 
analyses will be descriptive in nature 
 
 
 
• Revised the definitions of DFS and 
TTR to start from the time of 
randomization for both CR and NCR 
patients at the 3-month Visit 
 
 
 
• Deleted the exploratory endpoint of 
other resource utilization 
 
 
 
 
• Removed data review committee 
 
 
 
• Removed ET Visit from SoA and 
clarified that patients who 
discontinue from the study should 
have an EOS Visit performed 
 


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Protocol BL006 version 2.0 
 
87 
Version 
Date 
Description of Changes 
Brief Rationale 
2.0 
20 Dec 2021 • Updated Study BL005 from 
preliminary to final data 
 
 
 
• Added COVID-19 to the study 
risk assessment 
 
 
 
 
 
• Defined sexual abstinence and 
clarified that periodic abstinence is 
not an acceptable method of 
contraception 
 
 
 
 
• Clarified that hospitalization is not a 
requirement for the study 
 
 
 
• Clarified that access to treatment 
information by Sponsor personnel 
will be restricted by role 
 
 
 
• Clarified that patients with disease 
progression at the 3-month Visit or 
subsequent follow-up visits will be 
considered to have completed the 
study at that time 
 
 
 
 
• Revised Section 8.2.2 and added a 
new Appendix 1 (Guidance on 
Evaluation of Response) 
 
 
 
 
 
• Clarified that rectal examination 
(part of urology-oriented PE at 
Screening Visit) applies to both male 
and female patients 
 
 
 
• Deleted a planned supportive 
analysis of the primary endpoint 
based on propensity scores 
 
 
 
• Reorganized the protocol appendices 
to follow Section 11 (References) 
 
 

SAP_001.pdf: 
CONFIDENTIAL 
 
Statistical Analysis Plan: BL006 
UroGen Pharma Ltd. 
 
Version Final 1.0  
 
 
 
1 
 
Statistical Analysis Plan: BL006 
 
 Study Title: 
A Randomized, Controlled, Open-label Study of the 
Efficacy, Durability, and Safety of UGN-102 With or 
Without TURBT in Patients with Low Grade Intermediate 
Risk Non-Muscle Invasive Bladder Cancer (LG 
IR-NMIBC) (ATLAS) 
 
Study Number: 
BL006 
 
Study Phase:  
3 
 
Sponsor: 
UroGen Pharma Ltd. 
 
 
Version  
Final 1.0 
 
 
Date: 
17 Feb 2023 
 
Confidentiality Statement 
This document contains confidential and proprietary information and is 
not to be distributed to any third party. 
 
 
 
 
 
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Statistical Analysis Plan: BL006 
UroGen Pharma Ltd. 
 
Version Final 1.0  
 
 
 
2 
 
SIGNATURE PAGE 
PREPARED BY: 
Author 
Revathy Duvedi 
Senior Statistical Consultant 
____________________  
UroGen Pharma, Ltd. 
Signature 
 
Date: _______________ 
 
 
 
Reviewer 
Thalis Tsaklas 
Senior Biostatistician Consultant 
____________________ 
ClinChoice, Inc. 
Signature 
Date: _______________ 
 
 
 
 
 
 
APPROVED BY: 
 
Approver 
Soumi Lahiri, PhD 
Senior Director, Biostatistics 
____________________ 
UroGen Pharma, Ltd. 
Signature 
Date: _______________ 
 
Approver 
Sunil Raju, MD 
Vice President, Clinical Development 
____________________ 
UroGen Pharma, Ltd. 
Signature 
Date: _______________ 
 
 
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Statistical Analysis Plan: BL006 
 
 
Version Final 1.0 
 
 
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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 .................................................................................. 10 
3.2. 
Sample Size Justification ............................................................................ 10 
3.3. 
Randomization and Blinding ....................................................................... 10 
4. 
PLANNED ANALYSES........................................................................................... 11 
4.1. 
Interim Analyses ......................................................................................... 11 
4.2. 
Final Analysis ............................................................................................. 11 
5. 
ANALYSIS POPULATIONS ................................................................................... 11 
6. 
TREATMENT COMPARISONS .............................................................................. 12 
7. 
CHANGES TO THE PLANNED ANALYSES .......................................................... 12 
8. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ....................................... 12 
8.1. 
Multicenter Studies ..................................................................................... 13 
8.2. 
Other Strata and Covariates ....................................................................... 13 
8.3. 
Multiple Comparisons and Multiplicity ......................................................... 13 
9. 
DATA HANDLING CONVENTIONS ....................................................................... 13 
9.1. 
Premature Withdrawal and Missing Data .................................................... 14 
9.2. 
Derived and Transformed Data ................................................................... 14 
9.2.1. 
Reference Date............................................................................ 14 
9.2.2. 
Study Day for Safety Measures ................................................... 15 
9.2.3. 
Study Day for Efficacy.................................................................. 15 
9.2.4. 
Calculation of Durations ............................................................... 15 
9.2.5. 
Imputation of Partial Dates ........................................................... 15 
9.2.6. 
Baseline Definition ....................................................................... 16 
9.2.7. 
Change from Baseline ................................................................. 16 
9.2.8. 
Analysis Visit Window .................................................................. 16 
9.2.9. 
Multiple Assessments .................................................................. 17 
9.2.10. 
Actual Treatment ......................................................................... 18 
10. PATIENT DISPOSITION, DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS ............................................................................................. 18 
10.1. 
Disposition of Patients ................................................................................ 18 
10.2. 
Protocol Deviations ..................................................................................... 19 
10.3. 
Demographic and Baseline Characteristics ................................................. 19 
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10.4. 
General Medical History and Urothelial Carcinoma Related Medical 
History (UCMH) .......................................................................................... 20 
10.5. 
Prior and Concomitant Medications ............................................................ 20 
10.6. 
Prior and Concomitant Surgical Procedures ............................................... 21 
11. EFFICACY ANALYSES .......................................................................................... 21 
11.1. 
Primary Efficacy Analyses .......................................................................... 21 
11.1.1. 
Disease-Free Survival (DFS) ....................................................... 21 
11.2. 
Secondary Efficacy Analyses ...................................................................... 25 
11.2.1. 
Time to Recurrence (TTR) ........................................................... 25 
11.2.2. 
Complete Response Rate (CRR) at 3-Month Visit ....................... 26 
11.2.3. 
Visit Level Complete Response Rate (CRR) ................................ 27 
11.2.4. 
Duration of Response (DOR) ....................................................... 29 
11.2.5. 
Avoidance of Surgery (TURBT) for Treatment of LG IR-
NMIBC ......................................................................................... 29 
12. HEALTH RELATED QUALITY OF LIFE (HRQOL) ANALYSES .............................. 30 
13. HEALTH RESOURCE UTILIZATION ..................................................................... 31 
14. SAFETY ANALYSES ............................................................................................. 31 
14.1. 
Extent of Exposure of UGN-102 .................................................................. 32 
14.2. 
Adverse Events........................................................................................... 32 
14.3. 
Deaths and Serious Adverse Events ........................................................... 33 
14.4. 
Adverse Events Leading to Discontinuation of Study Treatment 
and/or Withdrawal from the Study ............................................................... 34 
14.5. 
Adverse Events of Special Interest ............................................................. 34 
14.6. 
Clinical Laboratory Evaluations ................................................................... 34 
14.6.1. 
Potentially Clinically Significant (PCS) Laboratory Values ............ 35 
14.6.2. 
Potentially Clinically Significant Abnormal Liver Function 
Tests ............................................................................................ 36 
14.7. 
Vital Signs................................................................................................... 37 
14.7.1. 
Potentially Clinically Significant (PCS) Vital Sign 
Abnormalities ............................................................................... 37 
14.8. 
General Physical Examination .................................................................... 38 
14.9. 
Urology-Oriented Examination .................................................................... 38 
15. PHARMACOKINETIC ANALYSES ......................................................................... 38 
16. PHARMACODYNAMIC AND BIOMARKER ANALYS ............................................. 38 
17. PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES ................................... 38 
18. PHARMACOGENETIC DATA ANALYSES ............................................................. 38 
19. REFERENCES ....................................................................................................... 38 
20. APPENDICES ........................................................................................................ 39 
Appendix 1 Imputation Rules for Missing or Partial Dates ...................................... 39 
Appendix 2 Laboratory CTCAE Grade Version 5.0 Criteria .................................... 42 
Appendix 3 Data Display Specifications ................................................................. 43 
 
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ABBREVIATIONS 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical (classification) 
BMI 
body mass index 
CI 
confidence interval 
CDISC 
Clinical Data Interchange Standards Consortium 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRR 
complete response rate 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
diastolic blood pressure 
DFS 
disease-free survival 
DOR 
duration of response 
eCRF 
electronic case report form 
EOS 
end of study 
HR 
hazard ratio 
HRQoL 
health related quality of life 
ICH 
International Council for Harmonisation 
IP 
investigational product 
IR 
intermediate risk 
ITT 
intent-to-treat 
LFT 
liver function test 
LG 
low grade 
LLN 
lower limit of the normal range 
LOCB 
last observation carried backward 
LOCF 
last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
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MMC 
Mitomycin C 
NCR 
non-complete response 
NPT 
non-protocol therapy 
NMIBC 
non-muscle invasive bladder cancer 
PCS 
potentially clinically significant 
PP 
per protocol 
PRO 
patient reported outcome 
PT 
preferred term 
QLQ-
NMIBC24 
24-item quality of life questionnaire for patients with NMIBC 
RD 
Recurrence disease 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
Statistical analysis system 
SBP 
systolic blood pressure 
SOA 
schedule of activities 
SOC 
system organ class 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TLFs 
tables, listings, figures 
TTR 
time to recurrence 
TURBT 
transurethral resection of bladder tumors 
ULN 
upper limit of the normal range 
WHO 
World health organization 
 
 
  
 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes all planned analyses for the Clinical Study 
Report (CSR) of study BL006 (ATLAS), a phase 3, randomized, controlled, open-label 
study of UGN-102 with or without transurethral resection of bladder tumors (TURBT) in 
patients with Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG 
IR-NMIBC). 
This SAP is written with due consideration of the recommendations outlined in the most 
recent International Council on Harmonisation (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: 
x Protocol, Version 2.0 dated 20 December 2021  
x Case report form (CRF), Version 6.1 dated 30 June 2022 
All decisions regarding final analysis, as defined in the SAP document, have been made 
prior to database lock and formal unblinding 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 efficacy of UGN-
102 with or without TURBT 
versus TURBT alone with respect 
to disease-free survival (DFS) in 
patients 
with 
Low 
Grade 
Intermediate Risk Non-Muscle 
Invasive Bladder Cancer (LG IR-
NMIBC). 
Disease-free survival (DFS) is defined as the time from 
randomization until the earliest date of any of the following 
events: 
x Failure to be rendered free of local disease at the 
3-Month assessment after the TURBT procedure. 
x Recurrence of low-grade disease after the 3-Month 
assessment (i.e., during the follow-up period). 
x Progression to high-grade disease. 
x Death due to any cause. 
Secondary 
 
1. To evaluate the efficacy of 
UGN-102 with or without TURBT 
versus TURBT alone with respect 
to: 
a) Time to Recurrence 
(TTR) 
b) Complete Response Rate 
(CRR) at 3-Month 
disease assessment 
1. The following efficacy endpoints will be evaluated: 
a) Time to recurrence (TTR) is defined as the time 
from randomization until the earliest date of 
recurrence of low-grade disease or progression to 
high-grade disease. 
b) Complete response rate (CRR), defined as the 
proportion of patients who achieved CR at the 3-
Month disease assessment.  
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OBJECTIVE 
ENDPOINT 
c) Duration of Response 
(DOR) 
d) Avoidance of surgery 
(TURBT) for treatment of 
LG IR-NMIBC 
2. To evaluate the safety profile of 
UGN-102 with or without TURBT 
versus TURBT alone. 
3. To assess the effect of UGN-102 
with or without TURBT versus 
TURBT alone on Patient Reported 
Outcomes 
(PROs) 
including 
disease 
related 
symptoms, 
functioning, and health-related 
quality of life (HRQoL). 
4. To evaluate visit level Complete 
Response Rate (CRR) 
c) Duration of response (DOR), defined as the time 
from first documented CR until the earliest date of 
any of the following events: 
x Recurrence of low-grade disease. 
x Progression to high-grade disease. 
x Death due to any cause. 
d) Proportion of patients requiring TURBT in each arm 
and average number of TURBT interventions per 
patient in each arm 
2. The safety profile of UGN-102 and TURBT will be 
evaluated 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. 
3. Changes from baseline in HRQoL measures assessed by 
European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire for Non-muscle 
Invasive 
Bladder 
Cancer 
patients 
(EORTC-QLQ-
NMIBC24). 
4. Observed CRR at scheduled disease assessment 
timepoints, defined as the proportion of patients who had 
CR at 3-Month disease assessment and maintained CR up 
to that particular follow-up disease assessment. 
Exploratory  
 
To explore potential differences in 
health resource utilization with 
UGN-102 vs TURBT in patients 
with LG NMIBC 
Number of patients hospitalized for non-elective reasons, 
total number and length of non-elective hospitalizations 
 
3. 
STUDY DESIGN 
This study is a global, randomized, controlled, open-label Phase 3 study designed to assess 
the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution (i.e., 
intravesical instillation) with or without TURBT (treatment arm) versus TURBT alone 
(control arm) in the treatment of patients with LG IR-NMIBC defined as 1 or 2 of the 
following: multiple tumors, solitary tumor > 3 cm, or recurrence (≥ 1 occurrence of LG 
NMIBC within 1 year of the current diagnosis at the initial Screening Visit) (Kamat, 2014). 
Eligible patients were treated with 6 weekly instillations of UGN-102 followed by TURBT 
only if needed, or with TURBT alone. 
Eligible patients were randomized in a 1:1 ratio to UGN-102 with or without TURBT or 
TURBT alone. Randomization was stratified by the presence of previous LG NMIBC 
episodes within 1 year of the current diagnosis at the initial Screening Visit (yes versus no). 
Starting at Day 1, patients randomized to the UGN-102 group were scheduled to receive 
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6 weekly intravesical instillations of UGN-102 followed by TURBT only if needed and 
patients randomized to the TURBT alone group were scheduled to undergo TURBT 
followed by repeat TURBT if needed.  
All patients (i.e., both treatment arms) were scheduled to return to the clinic at 
approximately 3 months from the initiation of treatment (i.e., 7 weeks ±1 week after the 
last weekly instillation for the UGN-102 treatment arm; and 12 weeks ±1 week after 
TURBT for the TURBT alone treatment arm) for their first evaluation of response. 
Following this initial evaluation, all patients who had a CR received no further treatment 
and entered the follow-up period of the study. Patients who had a non-complete response 
(NCR), residual disease, in either treatment arm had TURBT of any remaining lesions and 
then entered the follow-up period of the study. Note: If the Investigator determined that a 
formal TURBT in the operating room was unnecessary following cystoscopy and biopsy 
of remaining lesions (e.g., residual disease can be addressed by in office biopsy and/or 
fulguration), such an alternative procedure was permitted based on the Investigator’s 
medical judgment. 
Response was determined based on visual evaluation by cystoscopy (white light) 
(appearance, number, and size of any remaining lesions), histopathology of any remaining 
lesions, and voiding urine cytology. Details of the evaluation methods are available in 
Appendix 1 (Guidance on Evaluation of Response) of the protocol.  
The original plan was to follow patients up to 24 months or until disease recurrence, disease 
progression, or death was documented, whichever occurred first. But the study was closed 
early for business reasons after all patients completed their 15-Month visit (i.e. 12 months 
follow-up after primary disease evaluation at 3-Month) or until disease recurrence, disease 
progression, or death was documented, whichever occurred first.  
The study design is depicted in Figure 1 below. Schedules of activities from Screening to 
end of study (EOS) are available in protocol Section 1.3 and Section 1.4 for patients in the 
UGN-102 ± TURBT and TURBT alone treatment arms, respectively.  
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Figure 1:
Study Schema
3.1.
Statistical Hypothesis
UroGen Pharma Ltd. (Sponsor) closed enrollment in Study BL006 on 10 Nov 2021 in order 
to pursue an alternative development strategy for UGN-102 in patients with LG IR 
NMIBC. Although patients who were already randomized were permitted to continue their 
study participation until the EOS, the study is not powered to perform any hypothesis 
testing. Therefore, all analyses will be descriptive in nature.
3.2.
Sample Size Justification
As of 10 Nov 2021, 282 patients were randomized in this study.
3.3.
Randomization and Blinding
Patients were randomly assigned in a 1:1 ratio to UGN-102 with or without TURBT or 
TURBT alone by using Interactive Response Technology (IRT) system. Randomization 
was stratified by the presence of previous LG NMIBC episodes within 1 year of the current 
diagnosis at the initial Screening Visit (yes versus no). The randomization schedule was
generated by the ClinChoice randomization statistician, using SAS version 9.4 that 
incorporates a standard procedure for generating randomization numbers. One 
randomization list, using block randomization method was generated, and all centers are 
using the same list to minimize any imbalance in the number of patients assigned to each 
treatment arm. 
Open-label studies, particularly randomized ones, require a rigorous approach to protect 
trial and data integrity. Per ICH E9 and E10 Principles, blinding or masking is intended to 
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limit the occurrence of conscious and unconscious bias in the conduct and interpretation of 
a clinical trial arising from the influence that the knowledge of treatment may have on the 
recruitment and allocation of patients, their subsequent care, attitudes of patients to the 
treatments, assessment of endpoints, handling of withdrawals, exclusion of data from 
analysis and so on. A Trial Integrity Plan (TIP) was created to define data restrictions and 
data access for the randomized open-label Study BL006, sponsored by UroGen Pharma 
Ltd (UroGen) without compromising patient safety. Details of study blinding plan are 
provided in the Trial Integrity Plan version 1.1. 
4. 
PLANNED ANALYSES 
4.1. 
Interim Analyses 
No interim analysis is planned for this study. 
 
4.2. 
Final Analysis 
The final analysis of this study will be performed after all patients complete their 15-Month 
visit (i.e., 12 months follow-up after primary disease evaluation at 3-Month)  or until 
disease recurrence, disease progression, or death is documented, whichever comes first.  
5. 
ANALYSIS POPULATIONS 
For the purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Intent-to-Treat 
Analysis Set 
(ITT) 
The ITT comprises of all randomized patients regardless of whether 
the treatment was administered. Patients will be analyzed according to 
the treatment and strata they have been assigned to during the 
randomization procedure. Any patient who receives a randomization 
number will be considered to have been randomized. Efficacy analyses 
will be conducted using the ITT population. 
Safety Set 
The Safety Set includes all patients who received any dose of UGN-
102 (treatment arm) or at least one TURBT intervention (control arm). 
Patients will be analyzed according to the study treatment they actually 
received. All safety analyses will be conducted using the safety 
population. 
Per Protocol 
Set (PPS) 
The Per Protocol set (PPS) will include the subset of the patients in the 
Safety analysis set without major protocol deviations that would 
confound efficacy evaluation. All protocol deviations or conditions 
leading to exclusion from the PPS will be detailed in the protocol 
deviation plan. Sensitivity analyses of the primary endpoint of DFS 
may be performed using data from PPS if the PPS and ITT differ 
sufficiently. 
3-Month CR 
Set 
The 3-Month CR Analysis Set will consist of all patients from ITT set 
who achieved CR at 3-Month disease assessment (Study Visit 3). 
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Efficacy analyses of the secondary endpoints DOR and visit level CRR 
will be conducted using the 3-Month CR Set. 
Patients considered NCR at the 3-Month Visit could receive an alternative procedure (e.g., 
biopsy and/or fulguration) if a formal TURBT was unnecessary based on the Investigator’s 
medical judgment. All NCR patients at the 3-Month Visit, irrespective of their mode of 
treatment, will be included in the analysis. 
6. 
TREATMENT COMPARISONS 
The study is not powered to perform any hypothesis testing as described in Section 3.1. 
Therefore, all analyses will be descriptive in nature. Hazard ratios (HR) will be generated 
for the primary endpoint to understand the trend of any clinical benefit in the treatment arm 
versus the control arm. No statistical conclusions will be made. 
 
The following treatment descriptors will be used on all applicable displays: 
 
Treatment Group 
Data Display 
Order of Treatment 
Groups 
Code 
Description 
1 
UGN-102 ± TURBT 
UGN-102 ± TURBT 
1 
2 
TURBT Alone 
TURBT Alone 
2 
 
7. 
CHANGES TO THE PLANNED ANALYSES 
1. Definition of ITT analysis set is modified to include all randomized patient regardless 
of whether the treatment was administered.  
2. Full Analysis Set is not needed anymore and hence has been deleted.  
3. Definition for PPS is modified to be a subset of Safety analysis set. 
4. All analyses under this SAP are descriptive in nature. Mixed effect model for 
repeated measures (MMRM) will not be performed to evaluate the two treatment 
arms with respect to changes in the QLQ-NMIBC24 measures. 
5. Due to the change in the ITT definition, all health outcomes related analyses will be 
performed under Safety analysis set. 
6. The overall safety observation periods have been updated to: 
x Pre-treatment period: from day of patient’s informed consent to the day before 
administration of first treatment or TURBT, 
x Up to 3-months: from the First Dose date of UGN-102/ date of Initial TURBT 
Procedure to 3-Month Visit, and  
x Post 3-months: after 3-Month Visit until the end of the study.  
 
8. 
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 
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perform all data analyses, generate tables, figures, and listings. 
 
Unless otherwise stated, all listings will be sorted by treatment group, 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.  
 
Generally, summaries will be produced by treatment arms. All laboratory data will be 
presented using the International System of Units (SI) Units.  
 
Deviations from the analyses in the SAP will be identified in the CSR. 
 
8.1. 
Multicenter Studies 
It is anticipated that patient accrual will be spread thinly across centers and summaries of 
data by center would be unlikely to be informative; therefore, data from all participating 
centers will be pooled prior to analysis.  
 
A summary of the number of patients by country and by site will be provided. 
 
8.2. 
Other Strata and Covariates 
Prior to randomization, eligible patients are stratified by previous LG NMIBC episodes 
within 1 year (Yes versus No). 
 
For analysis purposes randomized strata from IRT will be used. Strata will also be captured 
on the electronic case report form (eCRF) and will be listed if this differs from the 
classification reported at the time of randomization. 
 
A table will be provided to summarize the number of patients within each category of the 
stratification variables for the ITT population.  
 
All statistical analyses, unless otherwise noted, will be stratified by the randomization 
stratification. 
 
8.3. 
Multiple Comparisons and Multiplicity 
Not applicable.  
 
9. 
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 
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Oncology algorithms. The analysis dataset specifications will clearly communicate the 
content and source of the datasets supporting the statistical analyses.  
 
9.1. 
Premature Withdrawal and Missing Data 
A patient will be considered to have completed the study if the patient completes all follow-
up visits in accordance with the Schedule of Activities (SoA), has a recurrence or 
progression during the follow-up period, dies during the study, or is still in follow-up when 
EOS is declared. 
 
A patient will be considered to have withdrawn from the study if the patient has not 
recurred, progressed, or died and is lost to follow-up, has withdrawn consent, or is no 
longer being followed at the Investigator’s discretion. 
 
All available time-to-event data will be analyzed using suitable statistical methods. For 
endpoints which determine the percentage of complete responders (CR), indeterminate 
responses will be imputed following the imputation rules described in Section 11.2.2 and 
Section 11.2.3.1. Patients who terminated the study early, prior to the first disease 
assessment at 3-Month, will be assumed to be NCRs and will be included in the 
denominator when calculating the percentages. 
 
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 
1 Imputation Rules for Missing or Partial Dates. 
 
All relevant data will be summarized and/or listed. Summaries of the number of patients 
who have discontinued study treatment, as well as details on those in follow-up will be 
provided. 
 
9.2. 
Derived and Transformed Data 
9.2.1. 
Reference Date 
There are three reference dates: 
 
x The reference date for age is the date of Informed Consent as age is an eligibility 
requirement. 
 
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x The safety reference date is the date of first instillation of UGN-102 in the 
UGN-102 ± TURBT arm or date of first TURBT procedure for patients in the 
TURBT Alone arm and will be used to calculate study day for safety measures. 
 
x The efficacy reference date is the date of randomization and will be used to 
calculate study day for efficacy measures and baseline characteristics (such as 
time since initial diagnosis), as well as efficacy durations. 
9.2.2. 
Study Day for Safety Measures 
If the date of interest occurs on or after the safety reference date then the safety study day 
will be calculated as (date of interest - safety reference date) + 1. If the date of interest 
occurs before the safety reference date, then the safety study day will be calculated as 
(date of interest – safety reference date). There is no safety study day 0.  
9.2.3. 
Study Day for Efficacy 
If the date of interest occurs on or after the efficacy reference date then efficacy study day 
will be calculated as (date of interest - efficacy reference date) + 1. If the date of interest 
occurs prior to the efficacy reference date then efficacy study day will be calculated as 
(date of interest – efficacy reference date). There is no efficacy study day 0. 
9.2.4. 
Calculation of Durations  
Durations (e.g., duration of adverse event, duration of response, time to recurrence between 
prior NMIBC episodes, etc.) will be calculated as stop date minus start date plus one. 
 
When reporting time to event durations (DFS, TTR, DOR) or any other duration in months, 
divide the number of days by 30.4375; to report in weeks divide the number of days by 7; 
to report in years divide the number of days by 365.25. These algorithms for time to event 
return decimal numbers and ignore the actual numbers of days in the months or years 
between start date and stop date. The "year" used in these algorithms is 365.25 days long, 
and the "month" is one twelfth of that year. 
 
9.2.5. 
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 to study time periods or 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.' 
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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 in Appendix 1. 
 
9.2.6. 
Baseline Definition 
For Safety analyses, baseline will be defined as the most recent non-missing value prior to 
the first instillation of UGN-102 for patients in UGN-102 ± TURBT arm or prior to the 
first TURBT for patients in TURBT alone arm, i.e., prior to Day 1. 
 
The baseline is defined as the last HRQoL assessment on or prior to randomization for the 
HRQoL analysis.  
 
9.2.7. 
Change from Baseline 
Change from baseline will be presented for HRQoL and safety data as described in 
Section 12 and Section 12 respectively. 
 
Change from baseline is calculated as: 
x For records occurring after baseline: visit value – baseline value. 
Percent change from baseline is calculated as: 
x For records occurring after baseline: ((change from baseline) / baseline value) * 
100. 
If either the baseline or visit value is missing, the change from baseline and/or percent 
change from baseline is set to missing as well. 
 
9.2.8. 
Analysis Visit Window 
A windowing convention will be used to determine the analysis value for a given study 
visit only for the following visit-based assessments: 
x Health related Quality of Life (HRQoL) 
x Urological exam 
x Clinical chemistry, hematology, and urinalysis 
x Vital signs 
The window for the visits following baseline will be constructed in such a way that the 
upper limit of the interval falls halfway between the two visits (the lower limit of the first 
post-Day 1 visit will be Day 2). If an odd number of days exists between two consecutive 
visits, then the upper limit will be taken as the midpoint value minus 1 day.
Due to the different schedule of assessments per treatment arm, the visit windows are 
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defined separately in the following tables. 
 
Table 2: Analysis windows for UGN-102 ± TURBT arm 
Analysis Visit 
Target Day 
Analysis Window (Study Day) 
Baseline 
< 1 
< 1 
Day 1 
1 
1 
Week 2 
8 
2 - 11 
Week 3 
15 
12 - 18 
Week 4 
22 
19 - 25 
Week 5 
29 
26 - 32  
Week 6 
36 
33 - 63 
Month 3 
90 
64 - 134 
Month 6 
180 
135 - 224 
Month 9 
270 
225 - 314 
Month 12 
360 
315 - 404 
Month 15 
450 
405 - 494 
Month 18 
540 
495 - 584 
Month 21 
630 
585 - 674 
Month 24 
720 
≥ 675  
 
Table 3: Analysis windows for TURBT Alone arm 
Analysis Visit 
Target Day 
Analysis Window (Study Day) 
Baseline 
< 1 
< 1 
Day 1 
1 
1 
Month 3 
90 
2 - 134 
Month 6 
180 
135 - 224 
Month 9 
270 
225 - 314 
Month 12 
360 
315 - 404 
Month 15 
450 
405 - 494 
Month 18 
540 
495 - 584 
Month 21 
630 
585 - 674 
Month 24 
720 
≥ 675  
 
9.2.9. 
Multiple Assessments 
All data will be reported according to the nominal visit date for which it was reported. 
Analysis windows will be applied during dataset creation for the summaries of clinical 
hematology, chemistry, urinalysis, vital signs, urological examination, and the HRQoL 
assessments. Both scheduled and unscheduled data will be included in the analysis 
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windows and the summary sections labelled as worst-case. 
 
One or more results for a particular variable may be obtained in the same visit window. In 
such an event, the result with the date closest to the expected visit date will be used in the 
analysis. If two observations are equidistant from the expected visit date, the later 
observation will be used in the analysis.  
If multiple assessments are reported on the same date for the same scheduled planned time, 
then the worst-case result will be analyzed, except for laboratory data reported from both 
central and local laboratories. If laboratory data is reported from both central and local 
laboratories with the same date, then the central laboratory data will be analyzed to provide 
consistency with measurements from other patients. 
 
Data from all assessments (scheduled and unscheduled), including multiple assessments, 
will be included in the listings. 
 
9.2.10. 
Actual Treatment 
If a patient’s actual treatment is the same as the randomized treatment, then actual treatment 
is the randomized treatment. If a patient receives a study treatment that is different from 
the randomized treatment, then actual treatment is the different treatment (the treatment 
actually received). A listing of patients with actual treatment deviating from the 
randomized treatment will be generated.  
 
10. 
PATIENT DISPOSITION, DEMOGRAPHICS AND OTHER 
BASELINE CHARACTERISTICS 
Unless otherwise stated, all tables and listings in this section will be based on the ITT 
population, and all summaries and data listings will use treatment labels as specified in 
Section 6. 
10.1. 
Disposition of Patients 
A summary of the number of patients in each of the analysis sets described in Section 5 
will be provided. In addition, the number of patients by country and site will be summarized 
by treatment arm using the ITT analysis set. A listing of patients excluded from analysis 
set along with the reasons will also 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 or withdrawal will 
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be presented in the order they are displayed in the eCRF. The corresponding listing will 
also be generated.  
10.2. 
Protocol Deviations 
All protocol deviations will be summarized and 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 ITT population. See the Protocol Deviation 
Management Plan (PDMP) for details of protocol deviations. 
Patients with major protocol deviations that would confound efficacy evaluation, would be 
excluded from the PPS. All protocol deviations or conditions leading to exclusion from the 
PPS will be detailed in the protocol deviation plan and will be finalized prior to the database 
lock (DBL). Sensitivity analyses of the primary endpoint DFS may be performed using 
data from PPS if the PPS and ITT differ sufficiently. 
 
10.3. 
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 the 
mean, standard deviation, minimum, median (quartiles), and maximum as appropriate. In 
addition, age will also be categorized and summarized by <65, ≥ 65 to < 75, ≥ 75 to < 85 
and ≥ 85. 
The count and percentage will be computed for sex, race and ethnicity. 
 
The following baseline prognostic factors used in the subgroup analyses will be provided 
by count and percentage: 
x Age categories (<65, ≥ 65; < 75, ≥ 75) 
x BMI category (<30 kg/m2, ≥ 30 kg/m2) 
x Disease history (number of previous LG NMIBC episodes, previous LG NMIBC 
episodes within 1 year of current diagnosis) 
x Smoking history (smoker, non-smoker)  
x Disease burden (tumor size: ≤ 3 cm, >3 cm; tumor count: single, multiple) 
x Prior TURBT to treat at least 1 prior episode of LG NMIBC (Yes, No) 
Smoking has been recognized as the strongest established risk factor for bladder cancer. 
Smoking related data has been collected in the eCRF in great details and will be 
summarized by: 
 
x Category for substance use (Cigarettes, Cigar, Pipe, Other, and any combination) 
x Status (Smoker vs Non-Smoker) 
x Duration (<10, 10-20, 21-30, >30 years) 
 
A summary of prior LG NMIBC along with its standard of care (TURBT) will be provided. 
Number of prior LG NMIBC, time to recurrence between NMIBC episodes, number of 
prior TURBT procedures, and time since last TURBT will be summarized using the mean, 
standard deviation, minimum, median (quartiles), and maximum as appropriate. In 
addition, the count and percentage will be computed for number of prior TURBT group (0, 
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1, 2, ≥ 3) and time since last TURBT procedure at the time of current diagnosis (≤ 365 
days, >365 days). A listing of prior NMIBC diagnosis and the TURBT procedures will also 
be generated. 
10.4. 
General Medical History and Urothelial Carcinoma Related 
Medical History (UCMH) 
Medical history reported terms will be coded to a SOC and PT using the most recent version 
of MedDRA Version 23.1 or later. Number and percent of patients reporting any medical 
history by SOC and PT for the ITT analysis set will be provided for each treatment group. 
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 ITT analysis 
Set. The summary table will be sorted by descending order of frequency of SOC in the 
UGN-102 ± TURBT column (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. 
The UCMH status at baseline will be summarized as: 
x Time in month between the date of initial diagnosis and baseline 
x Number of UCMH episodes 
x Staging of the UCMH episode (Noninvasive papillary carcinoma (Ta), Tumor 
invades lamina propria (T1), Tumor invades muscular propria (T2), Tumor invades 
perivesical tissue/fat (T3), Tumor invades prostate, uterus, vagina, pelvic wall or 
abdominal wall, Other) 
x Grade of the UCMH episode (Papillary urothelial carcinoma - low grade, Papillary 
urothelial neoplasm of low malignant potential, Urothelial carcinoma in situ, 
Papillary urothelial carcinoma - high grade, Other) 
x UCMH episode treated (Yes, No) 
x Treatment given for the prior episode of UC (TURBT, Fulguration, BCG, MMC, 
Other). 
 
10.5. 
Prior and Concomitant Medications 
All medications will be coded using the World Health Organization (WHO) Drug 
Dictionary, September 2020 version or later. The Anatomical Therapeutic Chemical (ATC) 
Level 2, Level 3 and preferred name will be used to list and summarize the data. Analysis 
of prior and concomitant medications use will be performed in the following manner:  
x  Prior medications: Any medication that were started and stopped prior to the first 
instillation of UGN-102 for patients in UGN-102 ± TURBT arm or prior to the first 
TURBT for patients in TURBT alone arm. 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 ITT analysis set. For computing percentages, the 
denominator will be the number of patients in the ITT analysis set.  
x Concomitant medications: Any prior medications that are ongoing or any new 
medication administered following the first instillation of UGN-102 for patients in 
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UGN-102 ± TURBT arm or following the first TURBT procedure for patients in 
TURBT alone 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 ITT analysis set. For computing percentages, the 
denominator will be the number of patients in the ITT analysis set.  
All prior and concomitant medications will be included in a data listing. 
10.6. 
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 ± TURBT arm or prior to the first TURBT for 
patients in TURBT alone arm. 
 
Concomitant surgical procedures are surgical procedures that were done following the first 
instillation of UGN-102 for patients in UGN-102 ± TURBT arm or the first TURBT for 
patients in TURBT alone arm 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). Prior and concomitant surgical procedures 
will be summarized similar to that described for medical history in Section 10.4.  
All prior and concomitant surgical procedures will be included in a data listing. 
11. 
EFFICACY ANALYSES 
Efficacy analyses will be based on the ITT population as defined in Section 5 or a subset 
of the ITT population as described for each analysis. All analyses will be presented by 
treatment arm.  
 
Efficacy assessments are based on cystoscopy, for-cause biopsy, and cytology to assess 
response status of a patient at each efficacy visit. Investigator assessments will be 
considered as primary assessments.  
 
11.1. 
Primary Efficacy Analyses 
11.1.1. 
Disease-Free Survival (DFS) 
DFS is the primary endpoint of this study, and it is defined as the time from randomization 
until the earliest date of failure to be rendered free of local disease at the 3-Month 
assessment after the TURBT procedure, recurrence of low-grade disease after the 3-Month 
assessment (i.e., during the follow-up period), progression to high-grade disease, or death 
due to any cause. 
NCR (i.e., residual disease) at the 3-Month disease assessment in the UGN-102 ± TURBT 
treatment arm is not considered as a DFS event because treatment failure is not an event in 
a neoadjuvant setting. However, having residual disease at the 3-month disease assessment 
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after the TURBT procedure (i.e., in the TURBT arm) will be considered as a DFS event. 
Progression to HG disease any time during the study (even at the 3-month disease 
assessment) will be considered as a DFS event in both arms. 
The date of documented recurrence or progression will be determined using the date of 
cystoscopy, biopsy, or cytology, whichever occurs first. The date of death (due to any 
cause) should be taken from the Record of Death page.  
 
Patients without any adequate post baseline disease assessments will be censored at the 
date of randomization. 
 
Patients who recurred (or progressed or died) after an extended lost to follow-up (period 
without adequate assessment), will be censored at their date of last adequate assessment 
prior to recurrence (or progression or death), even if subsequent information is available 
regarding recurrence (or progression or death). An adequate assessment is defined as an 
assessment where the visit level response is not missing, and not Indeterminate. A patient 
will be considered to have an extended lost to follow-up (i.e., missed two or more 
consecutive adequate assessments), if the patient did not have an adequate assessment 
during the time period of 210 days (6 months + 4 weeks ~ 6*30.4375+28) and then had a 
recurrence (or progression or death). 
 
If a recurrence (or progression or death) is observed after a single missing or Indeterminate 
disease assessment, the actual date of recurrence (or progression or death) will be used as 
the event date. 
 
Example (protocol defined schedule of follow-up disease assessments is every 3 months 
± 2 week): A patient had the disease assessments at 3 months (CR) - 6 months (CR) – 9 
months (missing) – 12 months (missing) - Recurrence. Then the DFS status of this patient 
will be censored, and the censoring date will be the date of 6-month visit. 
 
Non-Protocol Therapy (NPT) 
 
Non-Protocol Therapy (NPT) are prohibited concomitant anti-cancer medication or 
surgical procedures as outlined in Section 6.8 of the protocol. These medications will be 
identified via clinical review of the CONMEDS and Surgery datasets. If a patient received 
multiple NPTs, the earliest date will be considered as the start date of NPT. These dates 
will be used to define event or censoring dates for DFS, TTR and DOR. 
 
For patients who receive an NPT the following rules will apply: 
 
x If the start date of the NPT is partial (i.e., either missing the day but has the month 
and year available or missing both day and month), the imputation rules described in 
Table 11 and Table 13 of Appendix 1 will be applied. No imputation will be made for 
completely missing dates. 
x If the NPT is started prior to documented disease recurrence or progression, then DFS 
will be censored at the date of the last adequate assessment that is no later than the 
date of initiation of NPT (i.e., if an assessment occurs on the same day as the start of 
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NPT, the assessment will be used - as it will be assumed the assessment occurred 
prior to the start of NPT). The date of response at the last adequate assessment will be 
used as the censoring date. 
x If the NPT is started prior to the first disease assessment (i.e., 3-Month visit), then 
DFS will be censored at the date of randomization.  
x If a patient does not have any post-baseline adequate assessment, DFS will be 
censored at the date of randomization. 
x If a patient has neither recurrence or progression nor died nor started NPT, then DFS 
will be censored at the date of the last adequate assessment.  
A summary of the assignments for progression and censoring dates for DFS are specified 
in the following table. 
Table 4: Assignments for Event and Censoring Dates for DFS Analysis 
Situation 
Date of Event or Censoring  
Outcome 
No post-baseline adequate assessments1  
Randomization date 
Censored 
Received NPT prior to 3-Month disease 
assessment  
Randomization date 
Censored 
Received NPT after 3-Month disease 
assessment prior to documented 
recurrence or progression 
Date of last ‘adequate’ assessment1,3 on or 
prior to starting NPT2 
Censored 
Death prior to 3-Month disease 
assessment 
Date of death 
Event 
Progression at or prior to 3-Month disease 
assessment 
Date of progression3 
Event 
Residual disease at 3-Month disease 
assessment in TURBT Alone arm 
Date of NCR3 
Event 
Death between adequate assessment 
visits  
Date of death 
Event 
No recurrence or progression or death 
Date of last ‘adequate’ assessment1,3 
Censored 
No recurrence or progression and the last 
response evaluation is ‘indeterminate’  
Date of last ‘adequate’ assessment1,3 
Censored  
Recurrence or progression or death after 
more than two or more missed visits 
Date of last ‘adequate’ assessment1,3 prior to 
missed assessments 
Censored 
Disease recurrence or progression 
documented at or between scheduled 
visits 
Date of first recurrence or progression3 
Event 
1 An adequate assessment is defined as an assessment where the visit level response is not missing and not 
indeterminate. 
2 If recurrence/progression and NPT occur on the same day assume the recurrence/progression was 
documented first.  
3 The earliest of (i) Date of cystoscopy; or (ii) Date of biopsy, or (iii) Date of cytology. 
DFS will be analyzed based on the data observed in the ITT population, according to the 
treatment arm patients were randomized and previous LG NMIBC episodes within 1 year 
(Yes vs. No) as the strata assigned at randomization. The distribution of DFS will be 
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estimated using the Kaplan-Meier method. The estimated median, first, and third quartiles 
of DFS along with 95% CIs (Brookmeyer and Crowley, 1982) will be presented by 
treatment arm. A figure and a listing of DFS time will be provided.  
A stratified Cox regression model will be used to estimate the HR of DFS, along with 95% 
CIs (using the same strata information as above). No p-value will be generated. The HR 
will be generated to understand the trend of any clinical benefit in the treatment arm versus 
the control arm. No statistical conclusion will be made.  
A supplementary table showing the details of the number at risk, number of events, and 
number censored with the event time will also be displayed. 
 
11.1.1.1. 
Supportive Analyses for DFS 
11.1.1.1.1. Sensitivity Analysis 
The primary analysis for DFS may be repeated with data based on PPS, as described in 
Section 5, if the PPS and ITT differ sufficiently. 
The proportionality of hazard assumption of the DFS distribution functions will be 
evaluated by appropriate methods. 
Additionally, a sensitivity analysis for DFS will be conducted, where the recurrence or 
progression or death after more than two or more missed visits (i.e., after extended loss to 
follow-up) will be considered as event in the analysis. 
11.1.1.1.2. Subgroup Analysis 
Subgroup analyses will be performed on each level of the following factors using ITT 
population and a corresponding summary table will be produced. Additionally, a forest plot 
of estimated HRs with the 95% CI by subgroups will be presented. 
Subgroups will include (but not limited to): 
x Baseline age group (years): (< 75, ≥ 75)  
x BMI category (kg/m2): (< 30, ≥ 30) 
x Sex: (Male, Female)  
x Tumor size (cm): (≤ 3, > 3) 
x Tumor count: (Single, Multiple) 
x Previous LG NMIBC Episodes within 1 year: (Yes, No) 
x Previous LG NMIBC Episode (Yes, No) 
x Number of previous LG NMIBC episodes: (≤ 2, > 2) 
x Prior TURBT (Yes, No) 
x Smoking History: (Smoker, Non-smoker) 
Prior TURBT value ‘Yes’ indicates at least 1 prior episode of LG NMIBC was treated with 
TURBT. 
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Smoker category includes both former and current smokers; Non-smoker category includes 
patients who “Never” smoked. 
The HRs will be generated to understand the trend of any clinical benefit in the treatment 
arm versus the control arm in each of the subgroups. No statistical conclusions will be 
made. 
11.2. 
Secondary Efficacy Analyses 
11.2.1. 
Time to Recurrence (TTR) 
TTR analysis will be based on the ITT analysis set. TTR is defined as the time from 
randomization until the earliest date of recurrence of low-grade disease or progression to 
high-grade disease. Death will not be considered as an event in this analysis. If a patient 
has not had an event (recurrence or progression), TTR will be censored at the date of the 
last adequate disease assessment (i.e., assessment where visit level response is CR) or date 
of death. The rules for defining event and censoring are described in the following table.  
Table 5: Assignments for Event and Censoring Dates for TTR Analysis 
Situation 
Date of Event or Censoring  
Outcome 
No post-baseline adequate assessments1  
Randomization date 
Censored 
Received NPT prior to 3-Month disease 
assessment  
Randomization date 
Censored 
Received NPT after 3-Month disease 
assessment prior to documented 
recurrence or progression 
Date of last ‘adequate’ assessment1,3 on or 
prior to starting NPT2 
Censored 
Death prior to 3-Month disease 
assessment 
Date of death 
Censored 
Progression at or prior 3-Month disease 
assessment 
Date of progression3 
Event 
Residual disease at 3-Month disease 
assessment in TURBT Alone arm 
Date of NCR 
Event 
Death between adequate assessment 
visits  
Date of death 
Event 
No recurrence or progression or death 
Date of last ‘adequate’ assessment1,3 
Censored 
No recurrence or progression and the last 
response evaluation is ‘indeterminate’  
Date of last ‘adequate’ assessment1,3 
Censored  
Recurrence or progression or death after 
more than two or more missed visits 
Date of last ‘adequate’ assessment1,3 prior to 
missed assessments 
Censored 
Disease recurrence or progression 
documented at or between scheduled 
visits 
Date of first recurrence or progression3 
Event 
1 An adequate assessment is defined as an assessment where the visit level response is not missing and not 
indeterminate. 
2 If recurrence/progression and NPT occur on the same day assume the recurrence/progression was 
documented first.  
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3 The earliest of (i) Date of cystoscopy; or (ii) Date of biopsy, or (iii) Date of cytology. 
 
The distribution function of TTR will be estimated using the Kaplan-Meier method. The 
estimated median, first, and third quartiles times to the first documented disease recurrence 
or progression along with 95% CIs (Brookmeyer and Crowley, 1982) will be presented by 
treatment arm. A listing of TTR endpoint will also be provided.  
 
A stratified Cox regression model will be used to estimate the HR of TTR, along with 95% 
CIs. No p-value will be generated. The HR will be generated to understand the trend of any 
clinical benefit in the treatment arm versus the control arm. No statistical conclusion will 
be made. 
 
A supplementary table showing the details of the number at risk, number of events, and 
number censored with the event time will also be displayed. 
 
11.2.2. 
Complete Response Rate (CRR) at 3-Month Visit 
Complete response rate (CRR) is defined as the proportion of patients in the ITT population 
who achieved CR at the 3-Month disease assessment. Patient response will be evaluated 
by the investigator according to the evaluation of response (EOR) outlined in the protocol 
Appendix 1 and will be recorded on the 3-Month Evaluation of Response CRF page. 
If the response at the 3-Month Visit is Indeterminate, then it will be imputed as below: 
 
x If the patient required a TURBT or other alternative procedures based on the 
investigator’s judgment (e.g., intraoperative laser resection, office fulguration, 
office cold cup biopsy, etc.), to treat the residual disease observed at the 3-Month 
evaluation, then the 3-Month response will be imputed as ‘NCR.’ 
x Else if the patient did not have any disease assessment post 3-Month visit, then 
the 3-Month response will be imputed as ‘NCR’. 
x Otherwise, it will be imputed as a CR. 
If response cannot be imputed for a patient at the 3-Month visit (e.g., no follow-up visits 
beyond 3-Month), the patient will be considered as non-complete responders (NCR) for 
the purpose of the analysis and will be included in the denominator. The date of disease 
assessment associated to CR/ NCR will be determined using the date of cystoscopy, biopsy, 
or cytology, whichever occurs first. 
 
CRR will be presented by treatment arm 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 and using the Clopper-Pearson method (Clopper and Pearson, 
1934). In addition, reasons for non-complete response (NCR) comprised of ‘Residual 
Disease,’ ‘Progression to HG Disease,’ and ‘Indeterminate’ will be tabulated using the 
number and percentages of patients.  
 
This endpoint will also be analyzed for a subgroup of patients who had at least 1 prior 
episode of LG NMIBC which was treated with TURBT. 
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11.2.3. 
Visit Level Complete Response Rate (CRR)  
Observed CRR at scheduled disease assessment timepoints, is defined as the proportion of 
patients who had CR at the 3-Month disease assessment and maintained CR up to that 
particular follow-up disease assessment. This endpoint will be summarized only for CR 
patients at the 3-Month visit (i.e., 3-MONTHCR analysis set) by treatment arm. Patient 
response will be evaluated by the investigator according to the EOR in protocol Appendix 1 
and will be recorded on the follow-up Evaluation of Response CRF page. Missing visit 
level responses will be imputed as described in Section 11.2.3.1.  
Evaluation of response will be based on central laboratory results when unavailable local 
laboratory results will be used. When results from both central and local laboratories are 
available, central laboratory results will supersede the local laboratory results. 
If a patient receives any NPT during the follow-up period, the response status at all 
subsequent follow-up visits after the NPT start date will be considered as NCR. Patients 
who terminated the study early or patients who have indeterminate response (which are not 
confirmed by subsequent visits) will also be considered as NCR. 
Observed CRR will be presented with nominal 95% exact CI (Clopper-Pearson) for each 
treatment arm at each scheduled timepoint (i.e., 6-, 9-, 12- and 15-months visits). The 
denominator to calculate the proportion will include all patients who were CR at 3-month 
visit. 
This endpoint will also be analyzed for a subgroup of patients who had at least 1 prior 
episode of LG NMIBC which was treated with TURBT. 
 
11.2.3.1. 
Imputation of Missing Visit Level Response  
Some patients had disruptions to their visit schedules due to COVID-19 situation or due 
to the war situation in Europe, after completing their 3-Month Visit. As a result, 
scheduled visits beyond the 3-Month Visit were delayed (outside the protocol window) or 
missed. In some cases, if the unscheduled visit was closer to the next scheduled visit (still 
outside the protocol defined window), investigator decided not to bring the patient until 
the following scheduled visits. For example, if a patient missed 6-month scheduled visit, 
had a delayed visit at 8-Month, investigator may decide not to bring the patient for the 
9-month scheduled visit, but to bring the patient in for the 12-month visit.  
The following rules will be used to impute missing or indeterminate visit level responses: 
1. If any recorded response is CR, then all previous missing or indeterminate scheduled 
visits responses are CR (Patient A), using the method last observation carried 
backward (LOCB). 
2. If any recorded response is recurrence disease (RD), then all previous missing or 
indeterminate scheduled visits responses are RD (Patient B; Patient C), using the 
method last observation carried backward (LOCB); unless there is a previous CR 
response closer in time (days) to the scheduled visit in which case the visit response 
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will be CR (Patient D), using the method last observation carried forward (LOCF). In 
the case of ties, the scheduled visit response will be RD (Patient E). 
3. Otherwise, responses will not be carried forward to scheduled visits that have not 
occurred (Patient C; Patient E) 
Visit  
Target 
Day/ 
Study Day 
Visit 
Window 
Patient 
A 
Patient 
B 
Patient 
C 
Patient 
D 
Patient 
E 
3-Month  
90 (± 1 week) 
83-97 
CR 
CR 
CR 
CR 
CR 
6-Month  
180 (± 2 week) 
166-194 
U/CR 
U/ RD 
U/RD 
CR 
CR 
Unscheduled  
190 
 
 
 
 
 
CR 
Unscheduled  
220 
 
 
 
 
CR 
 
9-Month  
270 (± 2 week) 
256-284 
CR 
RD 
RD 
CR 
RD 
Unscheduled  
288 
 
 
 
 
 
RD 
Unscheduled  
300 
 
 
 
RD 
 
 
12-Month  
360 (± 2 week) 
346-374 
 
 
 
RD 
 
………. 
 
 
 
 
 
 
 
 
RD=Recurrence disease; U=Unknown/Indeterminate; Red implicates imputed response.  
To further explain ‘closer in time (days) to the scheduled visit,’ the following variables are 
defined:  
a= Study day of the CR unscheduled visit 
b=Lower limit of next scheduled visit (days) 
c= Upper limit of the next scheduled visit (days) 
d= Study day of the following RD visit 
 
If (b-a) < (d-c) then the response at the scheduled visit will be CR; otherwise, RD.  
For example, Patient D has a CR response on Study Day 220, 36 days before the beginning 
of the Visit 9 window. This patient also has a RD response on study day 346 (say), 62 days 
(346-284) after the end of the visit 9 window. Since the CR response is closer to the visit 
9, the response will be CR. 
 
A patient listing will be generated to display visit level responses as recorded in the CRF 
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along with derived responses (indicating the method of derivation, LOCF or LOCB). 
Evaluation based on local laboratory results will be flagged.  
 
If the 3-month EOR is ‘Indeterminate,’ it will be imputed using the rules defined in 
Section 11.2.2.  
 
11.2.4. 
Duration of Response (DOR)  
DOR will be summarized only for CR patients at the 3-Month visit (i.e., 3-MONTHCR 
analysis set) by treatment arm. DOR is defined as the time from first documented CR until 
the earliest date of recurrence of low-grade disease, progression to high-grade disease or 
death due to any cause. If a patient has not had an event (recurrence, progression, or death), 
DOR will be censored at the date of the last adequate disease assessment (i.e., assessment 
where visit level response is CR). The rules for defining recurrence and censoring are 
described in Table 4. Censoring rules will follow those of the primary DFS analysis defined 
in Section 11.1.1. 
The distribution function of DOR will be estimated using the Kaplan-Meier method. The 
estimated median, first, and third quartiles of DOR along with 95% CIs (Brookmeyer and 
Crowley, 1982) will be presented by treatment arm. A figure and listing of DOR endpoint 
will also be provided.  
A stratified Cox regression model will be used to estimate the HR of DOR, along with 95% 
CIs. No p-value will be generated. The HR will be generated to understand the trend of any 
clinical benefit in the treatment arm versus the control arm. No statistical conclusion will 
be made. 
A supplementary table showing the details of the number at risk, number of events, and 
number censored with the event time will also be displayed. 
Additionally, a sensitivity analysis for DOR will be conducted, where the recurrence or 
progression or death after more than two or more missed visits (i.e., after extended loss to 
follow-up) will be considered as event in the analysis.  
This endpoint will also be analyzed for a subgroup of patients who had at least 1 prior 
episode of LG NMIBC which was treated with TURBT. 
11.2.5. 
Avoidance of Surgery (TURBT) for Treatment of LG IR-NMIBC 
This analysis will be performed using the Safety analysis set. Patients confirmed to have 
had a non-complete response (NCR) in either treatment arm will undergo TURBT of any 
remaining lesions and will then enter the follow-up period of the study. If the Investigator 
determines that a formal TURBT in the operating room is unnecessary following 
cystoscopy and biopsy of remaining lesions, residual disease can be addressed by the 
following in office procedures based on the Investigator’s medical judgment: 
 
x Intraoperative Laser Resection 
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x Office Fulguration (Ablation, Cauterization) 
x Office Cold Cup Biopsy 
x Other 
Proportion of patients requiring TURBT (total and after 3-Month disease evaluation) in 
each arm will be summarized along with other in office alternative procedures. Number of 
TURBT intervention per patient will also be summarized using appropriate descriptive 
statistics.  
 
12. 
HEALTH RELATED QUALITY OF LIFE (HRQoL) 
ANALYSES 
Health Related Quality of Life (HRQoL) is a secondary endpoint of this study. The safety 
analysis set will be used for analyzing QoL data unless specified differently.  
HRQoL will be assessed using The EORTC QLQ-NMIBC24 Questionnaire provided in 
Appendix 2 of the protocol and summarized by treatment arm. These questionnaires will 
be completed by patients at screening and subsequent visits following the Schedule of 
Activities tables (protocol Section 1.3 and Section 1.4).  
 
The EORTC QLQ-NMIBC24 is a self-reported 24-item NMIBC specific instrument that 
assesses 11 domains: 2 functional scales or single item (sexual function, sexual enjoyment), 
and 9 symptom scales or single items (urinary symptoms, malaise, future worries, bloating 
and flatulence, male sexual problems, intravesical treatment issues, sexual intimacy, risk 
of contaminating partner, and female sexual problems).  
For the functional scales and symptom scales or single items, patients will be assessed as 
to how true each of the statements has been for them on a 4-point scale,  
1= not at all 
2= a little  
3= quite a bit 
4= very much. 
For the functional scale and items, a higher score reflects a more favorable level of 
functioning. Conversely, for the symptom scales or items, a higher score represents lower 
HRQoL. The scale score will be calculated with only those items for which all of the 
relevant questions have non-missing answers. For example: The scale score for Urinary 
Symptoms can only be calculated if Questions 31-37 all were answered.  
All scoring information specific to the QLQ-NMIBC24 is presented in Table 6. The scoring 
method of this questionnaire will consist of a calculation of a raw score, followed by a 
linear transformation to standardize the raw score so that the scores range from 0 to 100. 
Raw scores from the EORTC QLQ-NMIBC24 questionnaires will be transformed based 
on the scoring manual.  
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Table 6: Scoring 11 Domains of QLQ-NMIBC24 
 
Scale 
Number 
of Items 
(n) 
Item 
Range
* 
Item 
Numbers  
(I1, I2,…,In) 
Raw 
Score 
(RS) 
Symptom scales / items 
 
 
 
 
 
Urinary Symptoms 
US 
7 
3 
31- 37 
(I31 +…+ I37)/7 
Malaise 
MAL 
2 
3 
38, 39 
(I38 + I39)/2 
Intravesical treatment 
InV 
1 
3 
40 
I40 
Future worries 
FW 
4 
3 
41 - 44 
(I11+…+I44)/4 
Bloating and flatulence 
BAF 
2 
3 
45, 46 
(I45 + I46)/2 
Male sexual problems 
SXme
2 
3 
49, 50 
(I49 + I50)/2 
Sexual intimacy a 
SXI 
1 
3 
51 
I51 
Risk of contaminating 
SXCP 
1 
3 
52 
I52 
Female sexual problems a 
SXfem 
1 
3 
54 
I54 
Functional scales / items 
 
 
 
 
 
Sexual function 
SX 
2 
3 
47, 48 
(I47 + I48)/2 
Sexual enjoyment a 
SXEN 
1 
3 
53 
I53 
* “Item range” is the difference between the possible maximum and the minimum response to 
individual items. All items are scored 1 to 4, giving range = 3. 
a Items 51 to 54 are conditional questions and must only be scored if these are applicable to the patient. 
Functional scales: Score= {1 - (RS-1)/range} × 100 
Symptom scales/items: Score= {(RS-1)/range} × 100 
Summary statistics of the observed values will be provided for 11 domain scores at 
baseline, each planned visit, and worst-case post-baseline (includes both scheduled and 
unscheduled assessments) by treatment arm. The change from baseline for 11 domain 
scores will also be summarized with summary statistics at each above mentioned 
timepoints by treatment group. A listing of the 11 domain scores values will be produced 
for each patient. 
 
The baseline is defined as the last HRQoL assessment on or prior to randomization. 
 
13. 
HEALTH RESOURCE UTILIZATION 
Potential differences in health resource utilization with UGN-102 ± TURBT versus 
TURBT alone, is an exploratory objective of this study. Number of patients hospitalized 
due to non-elective reasons along with the duration of hospitalization will be summarized 
using appropriate descriptive statistics and safety analysis set by treatment arms.    
 
14. 
SAFETY ANALYSES 
All safety analyses will be based on the safety analysis set.  
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14.1. 
Extent of Exposure of UGN-102 
Treatment exposure of UGN-102 will be categorized as follows:  
x 1 instillation of UGN-102 
x 2 instillations of UGN-102 
x 3 instillations of UGN-102 
x 4 instillations of UGN-102 
x 5 instillations of UGN-102 
x 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 dose (mg) instilled at week 1 through week 6 will be 
presented.  
A data listing of treatment exposure will be presented. 
 
14.2. 
Adverse Events 
Adverse Events (AEs) will be coded according to the latest version of the Medical 
Dictionary for Regulatory Affairs (MedDRA). 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 events (TEAE) is defined as an AE that occurs 
on or after the day of the first instillation of UGN-102 for patients in the UGN-102 ± 
TURBT arm or the day of the initial TURBT for patients in TURBT alone arm; 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 AE of special interest (AESI) will be provided.  
Separate summaries will be provided for study treatment related TEAEs and procedure 
related TEAEs. A study treatment-related AE is defined as an AE for which the investigator 
classifies the relationship to study treatment as “Yes.” A worst-case scenario approach will 
be taken to handle missing relatedness data, i.e., the summary table will include events 
with the relationship to study treatment as ‘Yes’ or missing. 
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 ± TURBT column (alphabetically for ties), then PTs will be sorted by descending 
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order of frequency within each SOC (alphabetically for ties). The sort order for the PT will 
be based on their frequency in the treatment arm (UGN-102 ± TURBT). 
 
The overall observation period will be divided into three mutually exclusive time periods: 
1. Pre-treatment period: from day of patient’s informed consent to the day before 
administration of first treatment or TURBT 
2. Up to 3-months: from the First Dose date of UGN-102/ date of Initial TURBT 
Procedure to 3-Month Visit and  
3. Post 3-months: after 3-Month Visit until the end of the study. 
 
Some key TEAE tables will be summarized by the following time periods: overall (anytime 
during the study from the treatment start date), Up to 3-month and post 3-month. This will 
help to distinguish the AE profile of UGN-102 from TURBT (or other alternative) 
procedures as patients with residual disease at the 3-Month visit will undergo TURBT (or 
alternative procedures).  
Summaries based on the following subgroups will be provided for all TEAEs by PT and 
Time Period: 
x 
Age: < 65 years vs. ≥ 65 years  
x 
Sex: male vs. female 
 
All AEs will be listed.  
  
14.3. 
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).  
 
All serious TEAEs will be tabulated based on the number and percentage of subjects who 
experienced the event. Separate summaries will also be provided for study treatment related 
serious TEAEs and procedure related serious TEAEs. The summary tables will be 
displayed in descending order of incidence in the UGN-102 ± TURBT arm by PT and Time 
Period. 
 
A study treatment-related SAE is defined as an SAE for which the investigator classifies 
the relationship to study treatment as “Yes.” A worst-case scenario approach will be taken 
to handle missing data, i.e., the summary table will include events with the relationship to 
study treatment as ‘Yes’ or missing.  
 
A separate listing for SAEs will be generated.  
 
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14.4. 
Adverse Events Leading to Discontinuation of Study 
Treatment and/or Withdrawal from the Study 
The following categories of TEAEs will be summarized separately in descending order of 
incidence in combination arm by PT only and separate supportive listings will be generated 
with patient level details for those patients: 
 
x 
TEAEs Leading to Treatment Discontinuation  
x 
TEAEs Leading to Study Discontinuation 
 
14.5. 
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. For some events several AE 
preferred terms may be ‘collapsed.’ 
 
The following categories of AE of special interest will be summarized by treatment arm 
as permitted by data: 
x Allergic reactions 
x Bone marrow suppression 
x Genitourinary infections 
x Lower urinary tract symptoms 
x Voiding interruption due to urethral/penile edema (unrelated to prostatic 
hypertrophy) 
 
Additional AE 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 and by treatment arm. 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. In addition, onset and duration of the first 
occurrences for each type of events will be summarized if data permits. These summaries 
will be provided for each type of AESI separately. 
 
AESI will be flagged in the general AE listing. 
 
14.6. 
Clinical Laboratory Evaluations 
Samples for hematology, serum chemistry and urinalysis will be collected at Screening and 
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subsequent visits following the SoA tables (protocol Section 1.3 and Section 1.4). Samples will 
be tested at the central laboratory. Additional tests may be part of a clinical site’s local 
laboratory’s standard panel and therefore reported along with these specified tests. Data 
from all sources (central and local laboratories) will be combined. When results from both 
central and local laboratories are available, central laboratory results will supersede the 
local laboratory results.  
 
Summaries of laboratory parameters will include hematology and serum chemistry using 
standard units. Baseline will be defined as the latest non-missing assessment prior to the 
first instillation of UGN-102 for patients in the treatment arm or prior to the first TURBT 
for patients in the control arm. Changes in hematology and serum chemistry variables 
between baseline and each subsequent assessment will be calculated. For values recorded 
with a leading greater than or less than (‘>,’ ‘<’) symbol, the reported numeric value will 
be used for analysis and the value with the symbol will be included in the listings, unless 
otherwise specified. For example, a value of <0.01 will be analyzed as 0.01 and listed as 
<0.01. 
The summary of observed values of the laboratory 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 lab values. 
Summaries of worst-case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE version 5.0. (Appendix 2) These summaries will 
display the number and percentage of patients with a maximum post baseline grade 
increasing from their baseline grade. Any increase in grade from baseline will be 
summarized along with any increase to a maximum grade of 3 and any increase to a 
maximum grade of 4. Missing baseline grade will be assumed as grade 0. For laboratory 
tests that are graded for both low and high values, summaries will be done separately and 
labelled by direction, e.g., sodium will be summarized as hyponatremia and hypernatremia. 
 
For lab tests that are not gradable by CTCAE version 5.0, summaries of worst-case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes to 
normal or no changes from baseline, and increases to high will be summarized at each 
planned time. If a patient has a decrease to low and an increase to high during the same 
time interval, then the patient is counted in both the “Decrease to Low” categories and the 
“Increase to High” categories. 
 
Listing of patients with laboratory values outside the laboratory normal ranges will be 
generated. 
 
No summary table of urinalysis will be produced. Urinalysis laboratory values with 
change from baseline will be listed. 
 
14.6.1. 
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 
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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 in the following 
table. 
Table 7: 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  
14.6.2. 
Potentially Clinically Significant Abnormal Liver Function Tests 
There were no patients who met these criteria in the Phase 2 study (BL005). Patients 
meeting criteria for abnormal liver function tests (LFTs) by time point will be listed. 
Threshold values of interest for LFTs are provided in the following table. 
Table 8: 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 
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Parameter 
Criterion 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin; ULN = upper 
limit of normal 
 
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. 
14.7. 
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 tables (protocol Section 1.3 and Section 1.4). 
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 by treatment arm. 
14.7.1. 
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 
by treatment arm. 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 by 
treatment arm. 
The PCS criteria are shown in Table 9. 
Table 9: 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 
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Parameter 
PCS Criterion 
≥105 mmHg 
≥105 mmHg and increase of ≥15 mmHg from Baseline 
 
14.8. 
General Physical Examination 
General physical examinations as described in the Section 8.3.1 of the protocol, will be 
performed at the screening visit only. Abnormal results (clinically significant or not 
clinically significant) will be summarized and listed by body system by treatment arm.  
 
14.9. 
Urology-Oriented Examination 
Urology-oriented examinations as described in the Section 8.3.1 of the protocol, will be 
performed at screening and subsequent visits following the protocol SoA table (Section 1.3). 
Abnormal results (clinically significant or not clinically significant) will be summarized 
for each body system by planned visits, and worst-case post-baseline (includes both 
scheduled and unscheduled assessments) as time points by treatment arm. 
A listing of patients with abnormal urology examination findings either clinically 
significant or not clinically significant will be provided.  
15. 
PHARMACOKINETIC ANALYSES 
Not applicable. 
16. 
PHARMACODYNAMIC AND BIOMARKER ANALYS 
Not applicable. 
17. 
PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES 
Not applicable. 
18. 
PHARMACOGENETIC DATA ANALYSES 
 Not applicable. 
 
 
19. 
REFERENCES 
Brookmeyer R., Crowley J. A Confidence Interval for the Median Survival Time. 
Biometrics.Vol. 38, 1982:29-41.  
Clopper CJ and Pearson ES (1934). The use of confidence or fiducial limits illustrated in 
the case of the binomial. Biometrical, 26, 404-413. 
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20.
APPENDICES
Appendix 1 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 10: Imputation Rules of Adverse Event (AE) Start and End Dates
Dataset
Date
Missing 
Element
Rule
AE
Start 
Date
day, 
month, 
and year
x
No Imputation for completely missing dates
year
x
No Imputation if year is missing
day, 
month
x
If year of AE start date = year of study treatment start date, then set 
AE start date = Study treatment start date
x
Else set AE start date = 01JANYYYY
x
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
x
If month and year of start date = month and year of treatment start 
date, then set AE start date = study treatment start date.
x
Else set start date = 01MONYYYY.
x
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
x
No imputation for partial end dates will be performed
Table 11: Imputation Rules of Prior or Concomitant Medication (CM) Start and End 
Dates
Dataset
Date
Missing 
Element
Rule
CM
Start 
Date
day, 
month, 
and year
x
No Imputation for completely missing dates
year
x
No Imputation if year is missing
day, 
month
x
If year of CM start date = year of study treatment start date, then 
set CM start date = Study treatment start date
x
Else set CM start date = 01JANYYYY
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x
If imputed CM start date > CM end date (complete or imputed), 
then imputed CM start date should be set to CM end date.
day
x
If month and year of start date = month and year of treatment start 
date, then set CM start date = study treatment start date.
x
Else set start date = 01MONYYYY.
x
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
x
No imputation for partial end dates will be performed
day, 
month
x
Min (Last visit date, 31DECYYYY, Date of Death)
x
If imputed CM start date > CM end date (complete or imputed), 
then imputed CM start date should be set to CM end date.
day
x
Min (Last visit date, last day of the month, death day)
x
If imputed CM start date > CM end date (complete or imputed), 
then imputed CM start date should be set to CM end date.
Table 12: 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
x
No Imputation for completely missing dates
year
x
No Imputation if year is missing
day, 
month
x
If year of MH start date = year of inform consent date, then set MH
start date = min (01JANYYYY, Inform consent date -1).
x
Else if the year of MH start date < year of inform consent date, 
then set MH start date = 01JANYYYY.
x
If imputed MH start date > MH end date (complete or imputed), 
then imputed MH start date should be set to MH end date.
day
x
If month and year of start date = month and year of treatment start 
date, then set CM start date = Inform consent date -1.
x
Else set start date = 01MONYYYY.
x
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
x
No imputation for partial end dates will be performed
day, 
month
x
Min (Last visit date, 31DECYYYY, Date of Death)
x
If imputed MH start date > MH end date (complete or imputed), 
then imputed MH start date should be set to MH end date.
day
x
Min (Last visit date, last day of the month, death day)
x
If imputed MH start date > MH end date (complete or imputed), 
then imputed MH start date should be set to MH end date.
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Table 13: Imputation Rules of Prior or Concomitant Surgical Procedures (PR) Start 
Date
Dataset
Date
Missing 
Element
Rule
PR
Start 
Date
day, 
month, 
and year
x
No Imputation for completely missing dates
year
x
No Imputation if year is missing
day, 
month
x
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.
x
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
x
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.
x
Else set start date = 01MONYYYY.
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Appendix 2 Laboratory CTCAE Grade Version 5.0 Criteria 
Table 14: 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 
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 
 
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Lab Parameter 
Conventional 
Unit 
CTCAE Grade v5.0 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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 
(leukocytosis) 
×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 3 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 15: Table of Contents for Data Display Specifications 
Type 
Section 
Number 
Title 
Table 
Patient 
Info 
14.1.1 
Screened and Randomized Patients 
Table 
Patient 
Info 
14.1.2 
Summary of Analysis Sets 
Table 
Patient 
Info 
14.1.3 
Summary of Patient Enrollment by Country and Site 
Table 
Patient 
Info 
14.1.4.1 
Summary of Patient Disposition through the End of Treatment Period for UGN-
102 
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Type 
Section 
Number 
Title 
Table 
Patient 
Info 
14.1.4.2 
Summary of Patient Disposition through the End of Study 
Table 
Patient 
Info 
14.1.5 
Summary of Protocol Deviations 
Table 
Patient 
Info 
14.1.6.1 
Summary of Demographics and Baseline Characteristics 
Table 
Patient 
Info 
14.1.6.2 
Summary of Baseline Prognostic Factors 
Table 
Patient 
Info 
14.1.6.3 
Summary of Baseline Smoking History 
Table 
Patient 
Info 
14.1.7.1 
Summary of General Medical History 
Table 
Patient 
Info 
14.1.7.2 
Summary of Prior and Concurrent Urothelial Carcinoma Medical Condition 
Table 
Patient 
Info 
14.1.8.1 
Summary of Urothelial Carcinoma Related Medical History at Screening 
Table 
Patient 
Info 
14.1.8.2 
Summary of Prior NMIBC Episodes and Prior TURBT 
Table 
Patient 
Info 
14.1.9.1 
Summary of Prior Medications 
Table 
Patient 
Info 
14.1.9.2 
Summary of Concomitant Medications 
Table 
Patient 
Info 
14.1.10.1 
Summary of Prior Surgical Procedures 
Table 
Patient 
Info 
14.1.10.2 
Summary of Concomitant Surgical Procedures 
Table 
Patient 
Info 
14.1.11.1 
Summary of Duration of Follow-up 
Table 
Efficacy 
14.2.1.1 
Summary of Disease-free Survival 
Table 
Efficacy 
14.2.1.2 
Summary of Kaplan-Meier Estimates of Disease-free Survival 
Table 
Efficacy 
14.2.1.3 
Sensitivity Analysis: Summary of Disease-free Survival Ignoring Extended 
Loss to Follow-up 
Table 
Efficacy 
14.2.1.4 
Sensitivity Analysis: Summary of Disease-free Survival Per Protocol 
Analysis Set 
Table 
Efficacy 
14.2.1.5 
Subgroup Analysis: Summary of Disease-free Survival 
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Type 
Section 
Number 
Title 
Table 
Efficacy 
14.2.2.1.1 
Summary of Time to Recurrence 
Table 
Efficacy 
14.2.2.1.2 
Summary of Kaplan-Meier Estimates of Time to Recurrence 
Table 
Efficacy 
14.2.2.2.1a 
Summary of Response Rate at 3-Month Disease Assessment 
Table 
Efficacy 
14.2.2.2.1b 
Summary of Response Rate at 3-Month Disease Assessment for Patients with 
Prior TURBT 
Table 
Efficacy 
14.2.2.2.2a 
Summary of Response Rates at Scheduled Disease Assessments 
Table 
Efficacy 
14.2.2.2.2b 
Summary of Response Rates at Scheduled Disease Assessments for Patients 
with Prior TURBT 
Table 
Efficacy 
14.2.2.3.1a 
Summary of Duration of Response 
Table 
Efficacy 
14.2.2.3.1b 
Summary of Duration of Response for Patients with Prior TURBT 
Table 
Efficacy 
14.2.2.3.1a 
Summary of Duration of Response Ignoring Extended Loss to Follow-up 
Table 
Efficacy 
14.2.2.3.2a 
Summary of Kaplan-Meier Estimates of Duration of Response 
Table 
Efficacy 
14.2.2.3.2b 
Summary of Kaplan-Meier Estimates of Duration of Response for Patients with 
Prior TURBT 
Table 
Efficacy 
14.2.2.4 
Summary of Procedures for NMIBC During Study 
Table 
Health 
Outcomes 
14.2.2.5 
Summary of Change from Baseline in HRQoL 
Table 
Other 
14.2.3.1 
Summary of Patients Hospitalized for Non-Elective Reasons 
Table 
Safety 
14.3.1.1 
Overall Summary of Adverse Events by Time Period 
Table 
Safety 
14.3.1.2.1 
Incidence of Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term and Time Period 
Table 
Safety 
14.3.1.2.2 
Incidence of Treatment-Emergent Adverse Events by Preferred Term and Time 
Period 
Table 
Safety 
14.3.1.2.3 
Incidence of Treatment-Emergent Adverse Events by Preferred Term, Age and 
Time Period 
Table 
Safety 
14.3.1.2.4 
Incidence of Treatment-Emergent Adverse Events by Preferred Term, Sex and 
Time Period 
Table 
Safety 
14.3.1.3.1 
Incidence of Treatment-Emergent Adverse Events by Preferred Term and Worst 
Severity 
Table 
Safety 
14.3.1.3.2 
Incidence of Treatment-Emergent Adverse Events by Preferred Term and Worst 
Outcome 
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Type 
Section 
Number 
Title 
Table 
Safety 
14.3.1.4.1 
Incidence of Treatment Related Treatment-Emergent Adverse Events by System 
Organ Class, Preferred Term and Time Period 
Table 
Safety 
14.3.1.4.2 
Incidence of Treatment Related Treatment-Emergent Adverse Events by 
Preferred Term and Time Period 
Table 
Safety 
14.3.1.4.3 
Incidence of Procedure Related Treatment-Emergent Adverse Events by 
Preferred Term 
Table 
Safety 
14.3.2.1.1 
Incidence of Serious Treatment-Emergent Adverse Events by Preferred Term 
and Time Period 
Table 
Safety 
14.3.2.1.2 
Incidence of Treatment Related Serious Treatment-Emergent Adverse Events by 
Preferred Term and Time Period 
Table 
Safety 
14.3.2.1.3 
Incidence of Procedure Related Serious Treatment-Emergent Adverse Events by 
Preferred Term and Time Period 
Table 
Safety 
14.3.2.2.1 
Incidence of Treatment-Emergent Adverse Events Leading to Treatment 
Discontinuation by Preferred Term 
Table 
Safety 
14.3.2.2.2 
Incidence of Treatment-Emergent Adverse Events Leading to Study 
Discontinuation by Preferred Term 
Table 
Safety 
14.3.2.3.1 
Incidence of Treatment-Emergent Adverse Events of Special Interest by 
Category and Preferred Term 
Table 
Safety 
14.3.2.3.2 
Summary of Characteristics of Treatment-Emergent Adverse Event of Special 
Interest by Category 
Table 
Safety 
14.3.2.3.3 
Summary of Onset and Duration of the First Occurrences of Treatment-
Emergent Adverse Event of Special Interest 
Table 
Safety 
14.3.4.1.1 
Summary of Hematology Results: Observed Values 
Table 
Safety 
14.3.4.1.3 
Summary of Hematology Results: Change from Baseline with Respect to the 
Normal Range 
Table 
Safety 
14.3.4.2.1 
Summary of Chemistry Results: Observed Values 
Table 
Safety 
14.3.4.2.2 
Summary of Chemistry CTCAE Grade Changes from Baseline Grade 
Table 
Safety 
14.3.4.2.3 
Summary of Chemistry Results: Change from Baseline with Respect to the 
Normal Range 
Table 
Safety 
14.3.4.3 
Summary of Potentially Clinically Significant Laboratory Values by Time 
Point 
Table 
Safety 
14.3.5.1 
Summary of Vital Signs Results: Observed Values 
Table 
Safety 
14.3.5.2 
Summary of Potentially Clinically Significant Vital Signs by Time Point 
Table 
Safety 
14.3.6.1 
Abnormal General Physical Examination Results at Screening 
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Type 
Section 
Number 
Title 
Table 
Safety 
14.3.6.2 
Abnormal Urology-Oriented Examination Results 
Table 
Safety 
14.3.7 
Summary of Treatment Exposure of UGN-102 
Table 
Safety 
14.3.1.1 
Summary of UGN-102 Dose (mg) by Visit 
Listing Patient 
Info 
14.3.1.2.1 
Randomized and Actual Treatment 
Listing Patient 
Info 
16.2.1.1 
Reason for Study Discontinuation 
Listing Patient 
Info 
16.2.1.2 
Patients Discontinued from UGN-102 Treatment 
Listing Patient 
Info 
16.2.2.1 
Protocol Deviations 
Listing Patient 
Info 
16.2.2.2 
Patients with Inclusion/Exclusion Criteria Deviation 
Listing Patient 
Info 
16.2.3 
Reason for Excluding Patients from Analysis Sets Full Analysis Set 
Listing Patient 
Info 
16.2.4.1 
Demographics and Baseline Characteristics 
Listing Patient 
Info 
16.2.4.2 
Baseline Prognostic Factors 
Listing Patient 
Info 
16.2.4.3 
Smoking History 
Listing Patient 
Info 
16.2.4.4 
Medical History 
Listing Patient 
Info 
16.2.4.5 
Prior and Concurrent Urothelial Carcinoma Medical Condition 
Listing Patient 
Info 
16.2.4.6 
Prior NMIBC Diagnosis and TURBT History 
Listing Patient 
Info 
16.2.4.7 
Prior and Concomitant Medications 
Listing Patient 
Info 
16.2.4.8 
Prior and Concomitant Surgical Procedures 
Listing Safety 
16.2.5 
UGN-102 Administration 
Listing Efficacy 
16.2.6.1 
Visit Level Disease Assessment Based on Cystoscopy, Histopathology, and 
Cytology 
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Type 
Section 
Number 
Title 
Listing Efficacy 
16.2.6.2 
Evaluation of Visit Level Response 
Listing Efficacy 
16.2.6.3 
Disease-free Survival 
Listing Efficacy 
16.2.6.4 
Time to Recurrence 
Listing Efficacy 
16.2.6.5 
Duration of Response (DOR) 
Listing Health 
Outcomes 
16.2.6.6 
QLQ-NMIBC24 
Listing Safety 
16.2.7.1 
All Adverse Events 
Listing Safety 
16.2.7.2 
Serious Adverse Events 
Listing Safety 
16.2.7.3 
Treatment-emergent Adverse Events Leading to Treatment or Study 
Discontinuation 
Listing Safety 
16.2.7.4 
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 
16.2.9.1 
Vital Signs Results 
Listing Safety 
16.2.9.2 
Potentially Clinically Significant 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 
Figure 
Efficacy 
14.2.1.1a 
Kaplan-Meier Plot of Disease-free Survival 
Figure 
Efficacy 
14.2.1.1b 
Kaplan-Meier Plot of Disease-free Survival Ignoring Extended Loss to 
Follow-up 
Figure 
Efficacy 
14.2.1.2 
Hazard Ratios and 95% Confidence Intervals for Disease-free Survival by 
Subgroups 
Figure 
Efficacy 
14.2.2a 
Kaplan-Meier Plot of Duration of Response 
Figure 
Efficacy 
14.2.2b 
Kaplan-Meier Plot of Duration of Response Ignoring Extended Loss to Follow-
up 
 
 
 
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