A Phase 3 Single-Arm Study of UGN-102 for 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

24 Mar 2022 → ongoing

Decision date (initial)

2024-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Urogen Pharma Ltd.

External identifiers

EU CT number

2023-506680-34-00

EudraCT number

2021-005948-29

WHO UTN

U1111-1312-0682

ClinicalTrials.gov

NCT05243550

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the tumor ablative effect of UGN 102 in patients with LG NMIBC.

Secondary objectives 7

1. 1. To evaluate the durability of response with respect to DOR.
2. 2. To evaluate the durability of response with respect to DCR rate at scheduled disease assessment time points and DFS.
3. 3. To evaluate the safety and tolerability of intravesical instillations of UGN 102 in patients with LG NMIBC
4. Exploratory 1. To evaluate TTR following SOC treatment in patients who have NCR at the 3 month Visit.
5. Exploratory 2. To evaluate the preliminary responses following SOC treatment in 3-month CR patients who have disease recurrence or progression during the Follow-up Period.
6. Exploratory 3. To evaluate the impact of UGN-102 on subsequent SOC treatment in patients who have NCR at the 3-month Visit or disease recurrence or progression during the Follow-up Period
7. Exploratory 4. To assess the effect of UGN-102 on PRO measures including disease related symptoms and physical, mental, and social health.

Conditions and MedDRA coding

Non-Muscle Invasive Bladder Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Capable of giving 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 signing the ICF.
3. 3. Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening.
4. 4. History of LG NMIBC requiring treatment with TURBT. 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).
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 × upper limit of normal (ULN). • Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 × ULN. • Alkaline phosphatase (ALP) ≤ 2.5 × ULN. • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
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, 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 of childbearing potential (defined as premenopausal women who have not been sterilized).

Exclusion criteria 16

1. 1. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year.
2. 2. History of HG bladder cancer (papillary or carcinoma in situ [CIS]) in the past 2 years.
3. 3. Known allergy or sensitivity to mitomycin 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 grading of T1.
8. 8. Concurrent upper tract urothelial carcinoma (UTUC).
9. 9. Evidence of active urinary tract infection (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.

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-102) as determined by cystoscopy, for cause biopsy, and urine cytology.

Secondary endpoints 8

1. 1. DOR in patients who achieved CR at the 3 month Visit, defined as the time from the date of evidence of CR at the 3 month 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. DCR rate at scheduled disease assessment time points, defined as the proportion of patients who achieved CR at the 3-month Visit and maintained CR (ie, no detectable disease) up to that particular follow up disease assessment.
3. 3. DFS in patients who achieved CR at the 3 month Visit, defined as the time from first dose 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.
4. 4. The safety profile of UGN-102 will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs).
5. Exploratory 1. TTR in patients who were NCR (residual disease) at the 3-month Visit, defined as the time from the date of first treatment after NCR to the earliest date of recurrence or progression as determined using the date of cystoscopy, for cause biopsy, or cytology, whichever occurred first.
6. Exploratory 2. Number (%) of response outcomes evaluated at the first disease assessment visit after SOC.
7. Exploratory 3. Proportion of patients whose planned NMIBC treatment at baseline was downgraded following treatment with UGN-102 (eg, from TURBT to biopsy and/or fulguration).
8. Exploratory 4. Changes from baseline in patient scores on the QLQ C30 and QLQ-NMIBC24 questionnaires.

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, Ha-Ta'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 9

Locations

7 EU/EEA countries · 20 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 32 files

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

Application history

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