A Phase 3 Single-arm Study of UGN-103 for the Treatment of LG IR NMIBC.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Urogen Pharma Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Oct 2024 → ongoing

Decision date (initial)

2024-08-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

UroGen Pharma Ltd.

External identifiers

EU CT number

2023-507261-25-00

WHO UTN

U1111-1295-6474

ClinicalTrials.gov

NCT06331299

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy

To evaluate the tumor ablative effect of UGN-103, a novel formulation of UGN-102, in patients with LG NMIBC.

Secondary objectives 6

1. 1. To evaluate the durability of response with respect to DOR and DCR rate at scheduled disease assessment time points.
2. 2. To evaluate the safety and tolerability of UGN-103 in patients with LG NMIBC.
3. 3. To assess the PK profile of mitomycin in plasma in a subgroup of patients treated with UGN-103.
4. Exploratory 1. To assess the effect of UGN-103 on PRO measures including disease related quality of life and treatment satisfaction.
5. Exploratory 2. To identify mechanisms of sensitivity and/or resistance to UGN-103.
6. Exploratory 3. To evaluate preliminary responses following SoC treatment in patients who have an NCR at the 3-month Visit

Conditions and MedDRA coding

Nonmuscle Invasive Bladder Cancer

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Provide written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. 2. Patient must be ≥ 18 years of age at the time of informed consent.
3. 3. 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.
4. 4. 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.
5. 5. 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.
6. 6. Negative voiding cytology for HG disease within 8 weeks before Screening
7. 7. 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.
8. 8. Has an anticipated life expectancy of at least the duration of the trial.
9. 9. 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)

Exclusion criteria 17

1. 1. Received BCG treatment for UC within the previous 1 year.
2. 2. History of HG bladder cancer (papillary or CIS) in the past 2 years
3. 3. Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator’s opinion cannot be readily managed
4. 4. Clinically significant urethral stricture that would preclude passage of a urethral catheter
5. 5. History of: a. Neurogenic bladder. b. Active urinary retention. c. Any other condition that would prohibit normal voiding
6. 6. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC
7. 7. Current tumor staging of T1
8. 8. Concurrent UTUC
9. 9. Evidence of active UTI that in the investigator’s opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment
10. 10. Is pregnant or breastfeeding
11. 11. 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
12. 12. 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
13. 13. Has participated in a study with an investigational agent or device within 30 days of enrollment
14. 14. Has previously participated in a study in which they received UGN-102
15. 15. 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.
16. 16. 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
17. 17. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CRR, defined as the proportion of patients who achieved CR at the 3-month Visit (3 months after the first instillation of UGN-103) as determined by cystoscopy, for cause biopsy, and urine cytology.

Secondary endpoints 6

1. 1. DOR in patients who achieved CR at the 3-m Visit, defined as the time from the date of evidence of CR at the 3-m Visit to the earliest date of recurrence or progression as determined using the date of cystoscopy, for cause biopsy, or cytology, or death due to any cause, whichever occurred first.
2. 2. Safety and tolerability will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and l laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs)
3. 3. Concentration data and PK parameters (Cmax, tmax, and AUC
4. Exploratory 1. Changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires
5. Exploratory 2. DNA, RNA and/or protein biomarkers in tumor tissue
6. Exploratory 3. Number (%) of response outcomes evaluated at the first disease assessment visit after SoC

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Urogen Pharma Ltd.

Sponsor organisation

Urogen Pharma Ltd.

Address

9 HaTa'asiya

City

Ra'anana

Postcode

4365405

Country

Israel

Scientific contact point

Organisation

Urogen Pharma Ltd.

Contact name

Sunil Raju

Public contact point

Organisation

Urogen Pharma Ltd.

Contact name

John O’Reilly

Third parties 14

Locations

5 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications