Evaluation of UGN-103 (Mitomycin) Efficacy and Safety in Intermediate-Risk Low-Grade Nonmuscle Invasive Bladder Cancer: A Phase 3 Single-Arm Study

Trial ID: 2023-507261-25-00
Protocol: BL013
Sponsor: Urogen Pharma Ltd.

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Bladder cancer

Objectives

The primary objective of this study is to evaluate the **tumor ablative effect** of UGN-103, a novel formulation of UGN-102, in patients with low-grade nonmuscle invasive bladder cancer (LG NMIBC). This is clinically relevant as it aims to determine the efficacy of UGN-103 in reducing tumor burden in patients at intermediate risk of recurrence, potentially offering a new therapeutic option for this patient population.

Secondary objectives include:

Evaluating the durability of response with respect to duration of response (DOR) and disease control rate (DCR) at scheduled disease assessment time points.
Assessing the safety and tolerability of UGN-103 in patients with LG NMIBC.
Determining the pharmacokinetic (PK) profile of mitomycin in plasma in a subgroup of patients treated with UGN-103.
Exploratory objectives involve assessing the effect of UGN-103 on patient-reported outcomes (PRO) measures, including disease-related quality of life and treatment satisfaction, identifying mechanisms of sensitivity and/or resistance to UGN-103, and evaluating preliminary responses following standard of care treatment in patients who have a non-complete response (NCR) at the 3-month visit.

Participants

The clinical trial involves a total of **41 participants** diagnosed with **Nonmuscle Invasive Bladder Cancer** (NMIBC). The study population includes both male and female subjects, aged 18 years and older, who have been histologically confirmed to have low-grade NMIBC (Ta) through a cold cup biopsy. Participants were selected based on their history of at least one prior episode of NMIBC and must have intermediate risk disease, characterized by specific criteria such as the presence of multiple tumors, a solitary tumor larger than 3 cm, or early or frequent recurrence. All participants are required to have adequate organ and bone marrow function, as determined by routine laboratory tests, and a negative voiding cytology for high-grade disease within eight weeks before screening. The trial does not include a vulnerable population, and participants are expected to have an anticipated life expectancy that covers the duration of the trial. Both male and female participants are required to adhere to local regulations regarding contraceptive use during the study period. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

Plans and Procedures

The clinical trial is a **Phase 3**, single-arm, multicenter study designed to evaluate the efficacy and safety of UGN-103, a novel formulation of UGN-102, for the treatment of patients with low-grade nonmuscle invasive bladder cancer (NMIBC) at intermediate risk of recurrence. The trial aims to assess the tumor ablative effect of UGN-103 in this patient population. The study is expected to commence recruitment on October 1, 2024, and conclude by April 30, 2026. Participants will be involved in the trial for a maximum treatment period of six months, with the primary endpoint being the complete response rate (CRR) at the three-month visit, determined by cystoscopy, biopsy, and urine cytology.

The trial design includes a sequence of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as histologically confirmed low-grade NMIBC, intermediate risk disease, and adequate organ function. Following the screening, participants will undergo regular follow-up visits to monitor treatment response and safety. The end-of-study visit will evaluate the overall treatment outcomes and any adverse events. Participants are expected to adhere to the study protocol, and any deviation or occurrence of high-risk factors may lead to early termination from the study.

Key elements of the research methodology include the administration of UGN-103 as a **powder for intravesical solution**, with a maximum daily dose of 75 mg and a total dose not exceeding 450 mg over the treatment period. The study will also collect data on secondary endpoints such as duration of response, safety, tolerability, and pharmacokinetic parameters. Exploratory endpoints will investigate changes in quality of life scores and potential biomarkers in tumor tissue. The trial is not classified as low intervention and does not involve a pediatric formulation. Participants must provide informed consent and comply with contraceptive requirements if applicable.

Treatment

The clinical trial involves the administration of **UGN-103 (Mitomycin)**, a novel formulation designed for the treatment of patients with low-grade nonmuscle invasive bladder cancer (NMIBC) at intermediate risk of recurrence. The pharmaceutical form of UGN-103 is a **powder for intravesical solution**, which is specifically prepared for **intravesical use**. The active substance in this formulation is **Poloxamer 407**, a polymer that facilitates the delivery of the therapeutic agent. The maximum daily dose of UGN-103 is 75 mg, with a total maximum dose of 450 mg over the course of the treatment. The treatment period is limited to a maximum of 6 weeks. The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

In this study, UGN-103 is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed to evaluate the tumor ablative effect of UGN-103, and as such, the focus is on the efficacy and safety of this specific formulation. The study does not include any pediatric formulations, and the product is not classified as an orphan drug. The trial is conducted under the sponsorship of UROGEN PHARMA LTD., ensuring that all regulatory and ethical standards are maintained throughout the study.

Efficacy

The efficacy of UGN-103, a novel formulation of UGN-102, will be assessed in a Phase 3, single-arm, multicenter study targeting patients with low-grade nonmuscle invasive bladder cancer (NMIBC) at intermediate risk of recurrence. The primary endpoint for evaluating efficacy is the Complete Response Rate (CRR), defined as the proportion of patients achieving a complete response (CR) at the 3-month visit following the first instillation of UGN-103. This will be determined through cystoscopy, for-cause biopsy, and urine cytology.

Secondary endpoints include the Duration of Response (DOR) in patients who achieved CR at the 3-month visit. DOR is defined as the time from the date of evidence of CR to the earliest date of recurrence, progression, or death due to any cause, as determined by cystoscopy, biopsy, or cytology. Safety and tolerability will also be evaluated through the reporting of adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs), alongside standard clinical and laboratory tests such as hematology, chemistry, urinalysis, physical examination, and vital signs.

Exploratory endpoints will assess changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires, as well as the evaluation of DNA, RNA, and/or protein biomarkers in tumor tissue. The number and percentage of response outcomes will be evaluated at the first disease assessment visit after the standard of care. These assessments will provide comprehensive data on the efficacy of UGN-103 in the specified patient population.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Provide written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Patient must be ≥ 18 years of age at the time of informed consent.
Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. Note: This is a diagnostic biopsy to demonstrate histopathology of tumor and resection of the tumor is not to be performed. Residual tumor must be present and documented after biopsy and before instillation of study treatment.
History of at least 1 prior episode of NMIBC. Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened.
Has intermediate risk disease, defined as having 1 or 2 of the following: a. Presence of multiple tumors. b. Solitary tumor > 3 cm. c. Early or frequent recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial Screening Visit) Note: Patients with all 3 factors are considered high risk and are not eligible to participate.
Negative voiding cytology for HG disease within 8 weeks before Screening
Has adequate organ and bone marrow function as determined by routine laboratory tests as below: • Leukocytes ≥ 3,000/μL (≥ 3 × 109/L). • Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 109/L). • Platelets ≥ 100,000/μL (≥ 100 × 109/L). • Hemoglobin ≥ 9.0 g/dL. • Total bilirubin ≤ 1.5 × ULN. • AST and ALT ≤ 2.5 × ULN. • ALP ≤ 2.5 × ULN. • eGFR ≥ 30 mL/min.
Has an anticipated life expectancy of at least the duration of the trial.
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 female partner is 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 (ie, less than 1% per year) when used consistently and correctly, such as implants, injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (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, postovulation 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 of childbearing potential (defined as premenopausal women who have not been sterilized)

cancel

Exclusion Criteria

Received BCG treatment for UC within the previous 1 year.
History of HG bladder cancer (papillary or CIS) in the past 2 years
Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator’s opinion cannot be readily managed
Clinically significant urethral stricture that would preclude passage of a urethral catheter
History of: a. Neurogenic bladder. b. Active urinary retention. c. Any other condition that would prohibit normal voiding
Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC
Current tumor staging of T1
Concurrent UTUC
Evidence of active UTI that in the investigator’s opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment
Is pregnant or breastfeeding
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
History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous TURBT
Has participated in a study with an investigational agent or device within 30 days of enrollment
Has previously participated in a study in which they received UGN-102
Has any other active malignancy requiring treatment with systemic anticancer therapy (eg, chemotherapy, immunotherapy, radiation therapy). Superficial cancers such as cutaneous basal cell or squamous cell carcinomas that can be treated locally are allowed.
Has any other clinically significant medical or surgical condition that in the investigator’s opinion could compromise patient safety or the interpretation of study results
Where applicable per country regulation, the patient must not be currently committed to an institution by virtue of an order issued by either judicial or administrative authorities

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	01 Oct 2024	16
Estonia	Not Recruiting	01 Oct 2024	7
Latvia	Not Recruiting	01 Oct 2024	8
Romania	Not Recruiting	01 Oct 2024	13
Spain	Not Recruiting	01 Oct 2024	13