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This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the ability of the adenoviral vector to transfect cells in the bladder wall.
Criteria for Evaluation:
Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.
Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rAd-IFN Dose 1x10^11vps/ml | Experimental | Subjects will be randomly assigned to one of two INSTILADRIN arms. |
|
| rAd-IFN dose 3x10^11 vps/ml | Experimental | Subjects will be randomly assigned to one of two INSTILADRIN arms. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INSTILADRIN | Drug | The INSTILADRIN components will be mixed with a diluent. The total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of High Grade-Recurrence Free Survival at 360 Days | Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy. | 360 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of rAd-IFN/Syn3 | Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class. | 360 Days |
| Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days). |
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Inclusion Criteria:
Aged 18 years or older at the time of consent
Able to give informed consent
Subjects with high grade BCG-refractory or relapsed NMIBC including
Relapse is defined as recurrence within 1 year after a complete response to BCG treatment
Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
Available for the whole duration of the study
Life expectancy >2 years, in the opinion of the investigator
ECOG status 2 or less
Absence of upper tract urothelial carcinoma
Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion.
Adequate laboratory values.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Colin Dinney, MD | M.D. Anderson Cancer Center | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40194933 | Derived | Konety BR, Lotan Y, Myers A. Safety of nadofaragene firadenovec-vncg: review of data from phase 2 and phase 3 studies. Can J Urol. 2025 Mar 18;32(1):29-36. doi: 10.32604/cju.2025.064710. | |
| 28834453 | Derived | Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM, Gomella LG, Kamat AM, Lotan Y, Svatek RS, Bivalacqua TJ, Grubb RL 3rd, Krupski TL, Lerner SP, Woods ME, Inman BA, Milowsky MI, Boyd A, Treasure FP, Gregory G, Sawutz DG, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical rAd-IFNalpha/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017 Oct 20;35(30):3410-3416. doi: 10.1200/JCO.2017.72.3064. Epub 2017 Aug 23. |
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A manuscript will be published on the results of the study
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| ID | Title | Description |
|---|---|---|
| FG000 | rAd-IFN Dose 1x10^11vps/ml | Patients were randomized to the 1x10^11vps/ml rAd-IFN/Syn3 arm. A 75 mL dose of rAd-IFN/Syn3 was given as a single, one-hour intravesical administration and, depending on clinical response, was repeated every 90 Days up to a maximum of 4 instilations. |
| FG001 | rAd-IFN Dose 3x10^11 Vps/ml | Patients were randomized to the 3x10^11vps/ml rAd-IFN/Syn3 arm. A 75 mL dose of rAd-IFN/Syn3 was given as a single, one-hour intravesical administration and, depending on clinical response, was repeated every 90 Days up to a maximum of 4 instilations. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | rAd-IFN Dose 1x10^11vps/ml | Patients were randomly assigned to the 1x10^11vps/ml of rAd-IFN/Syn3 arm. |
| BG001 | rAd-IFN Dose 3x10^11 Vps/ml | Patients were randomly assigned to the 3x10^11vps/ml of rAd-IFN/Syn3 arm. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of High Grade-Recurrence Free Survival at 360 Days | Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy. | Posted | Count of Participants | Participants | 360 Days |
|
From dosing day 1 up to 12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rAd-IFN Dose 1x10^11 Vps/ml | Patients were randomized to the 1x10^11 vps/ml INSTILADRIN arm. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | MedDRA 15.0 | Systematic Assessment | Secondary to carotid artery stenosis - not related to drug; grade 3; resolved |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Sawutz, PhD | FKD Therapies Oy | 416-607-9515 | david.sawutz@fkdtherapies.com |
| ID | Term |
|---|---|
| D000093284 | Non-Muscle Invasive Bladder Neoplasms |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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The participant did not know if they received a high or low dose.
|
All patients were evaluated 3 Months (90 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. |
| 90 Days |
| Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days). | All patients were evaluated 6 Months (180 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. | 180 Days |
| Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days). | All patients were evaluated 9 Months (270 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received a final dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. | 270 Days |
| Incidence of Cystectomy in All Patients | This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set. | 360 Days |
| Overall Survival in All Patients. | Overall survival was defined as the number who survived from the first dose of rAd-IFN/Syn3 to the end of the primary assessment (360 Days) or Withdrawal. | 360 Days |
| Number of Patients With Elevated Levels of Viral Vector in Blood | The level of viral vector as measured by qPCR in blood was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | 103 Days |
| Number of Patients With Elevated Levels of Viral Vector in Urine | The level of viral vector as measured by qPCR in urine was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | 103 Days |
| Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | The levels of serum IFN alpha2b protein as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 91 (pre-dose), Day 92, Day 94, Day 103, Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | 360 Days |
| Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | The levels of urine IFN alpha2b protein as measured by ELISA were measured in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that did not have recurrence of HGD and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | 103 Days |
| Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | The levels of serum anti-IFN alpha2b antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | 360 Days |
| Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | The levels of serum anti-adenovirus type 5 antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | 360 Days |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Subjects were randomly assigned to the 1x10^11 vps/mI rAd-IFN/Syn3 arm. |
| OG001 | rAd-IFN Dose 3x10^11vps/ml | Patients were randomly assigned to the 3x10^11vps/ml rAd-IFN/Syn3 arm. |
|
|
|
| Secondary | Safety of rAd-IFN/Syn3 | Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| Secondary | Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days). | All patients were evaluated 3 Months (90 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. | All patients at 90 Days were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated. | Posted | Count of Participants | Participants | 90 Days |
|
|
|
| Secondary | Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days). | All patients were evaluated 6 Months (180 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. | All patients receiving a dose at 90 Days were assessed at 180 Days for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated. | Posted | Count of Participants | Participants | 180 Days |
|
|
|
| Secondary | Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days). | All patients were evaluated 9 Months (270 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received a final dose. Data are presented as the number and percent of patients with High-Grade disease recurrence. | All patients that received a dose at Day 180 were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated. | Posted | Count of Participants | Participants | 270 Days |
|
|
|
| Secondary | Incidence of Cystectomy in All Patients | This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set. | The data are presented as the number of patients per dose group having a cystectomy during the 360 days of the study. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| Secondary | Overall Survival in All Patients. | Overall survival was defined as the number who survived from the first dose of rAd-IFN/Syn3 to the end of the primary assessment (360 Days) or Withdrawal. | The data are presented as the number of patients who survived the study (360 Days). All patients were monitored for this endpoint. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| Secondary | Number of Patients With Elevated Levels of Viral Vector in Blood | The level of viral vector as measured by qPCR in blood was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | Data are reported as number of patients demonstrating viral vector by qPCR in blood. | Posted | Count of Participants | Participants | 103 Days |
|
|
|
| Secondary | Number of Patients With Elevated Levels of Viral Vector in Urine | The level of viral vector as measured by qPCR in urine was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | Data are reported as number of patients demonstrating increased levels of viral vector by qPCR in urine. | Posted | Count of Participants | Participants | 103 Days |
|
|
|
| Secondary | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | The levels of serum IFN alpha2b protein as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 91 (pre-dose), Day 92, Day 94, Day 103, Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | Data are reported as the number of patients with increased levels of IFN alpha2b protein in serum. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| Secondary | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | The levels of urine IFN alpha2b protein as measured by ELISA were measured in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that did not have recurrence of HGD and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103. | Data are reported as the number of patients with elevated levels of IFN alpha2b levels in urine. | Posted | Count of Participants | Participants | 103 Days |
|
|
|
| Secondary | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | The levels of serum anti-IFN alpha2b antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | Data are reported at Number of Patients with a Positive Titre. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| Secondary | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | The levels of serum anti-adenovirus type 5 antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal. | Data are reported at Number of Patients with a Positive Titer. | Posted | Count of Participants | Participants | 360 Days |
|
|
|
| 3 |
| 21 |
| 20 |
| 21 |
| EG001 | rAd-IFN Dose 3x10^11vps/ml | Patients were randomized the 3x10^11 vps/ml INSTILADRIN arm. | 2 | 19 | 19 | 19 |
|
| Sepsis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment | not related to drug; grade 3; resolved |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment | related to drug; grade 3; resolved |
|
| Coronary artery occlusion | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment | Coronary artery blockage; not related to drug; grade 3; resolved |
|
| Carotid artery occlusion | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment | Right carotid blockade |
|
| Renal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment | Left renal pelvis tumor - not related to drug; grade 3; resolved |
|
| Nephroureterectomy | Surgical and medical procedures | MedDRA 15.0 | Non-systematic Assessment | not related to drug; grade 3; resolved |
|
| Functional gastrointestinal disorder | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment | delayed return of bowel function; not related to drug; grade 3; resolved |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment | worsening of back pain; related to disease; not related to drug; grade 3; resolved |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment | acute renal failure, pre-renal (dehydration); related to drug; grade 3; resolved |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Blurred Vision | Eye disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Frequent Bowel Movements | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Oesophageal Dilatation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Facial Pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Fatique | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Feeling Cold | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Infusion Site Reactions | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Gasteroenteritis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Nasophanryngitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Skin Infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Tooth Abscess | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
|
| Clavicle Fracture | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 15.0 | Non-systematic Assessment |
|
| Blood Creatinine Increase | Investigations | MedDRA 15.0 | Non-systematic Assessment |
|
| Glycosylated Hemoglobin Increase | Investigations | MedDRA 15.0 | Non-systematic Assessment |
|
| pH Urine Decreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
|
| Urine Output DeEcreased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Fluid Retention | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Oedemia Peripheral | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Intervertrebral Disc Degeneration | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Joint Range of Motion Decreased | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Basal Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Lentigo Maligno Stage Unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Renal Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Seborrhoeic Keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Transitional Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
|
| Carotid Artery Occlusion | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Carotid Artery Stenosis | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Neuropathy Peripheral | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Restless Leg Syndrome | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Sinus Headache | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Mental Status Change | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Bladder Discomfort | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Bladder Pain | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Bladder Perforation | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hematuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Incontinence | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Micturition Urgency | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Nocturia | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Polyuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Renal Failure | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Renal Pain | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Urethral Stenosis | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Urinary Incontinence | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Urinary Retention | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Urinary Tract Disorder | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Urine Flow Decreased | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Prostatic Hemorrhage | Reproductive system and breast disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Actinic Keratosis | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dermatitis Contact | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Erythemia | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hyperhydrosis | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Swelling Face | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Nephroureterectomy | Surgical and medical procedures | MedDRA 15.0 | Non-systematic Assessment |
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| Aortic Stenosis | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Arterial Hemorrhage | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Eye Pain | Ear and labyrinth disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Facial Pain | General disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
|
| Coronary Artery Occlusion | Cardiac disorders | MedDRA 15.0 | Non-systematic Assessment |
|
Sponsor will complete its review within the review period and will have authority to require that the Institution and/or Investigator delete from the disclosure of any reference to Confidential Information, other than results.
| D001749 |
| Urinary Bladder Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| Day 103 |
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| Day 12 |
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| Pre-Dose Day 180 |
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| Pre-Dose Day 270 |
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| Pre-Dose Day 270 |
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