Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults with High-grade Non-muscle Invasive Bladder Cancer (Phase 1b) (ADVANCED-1)

A Phase 1a/b Dose Finding, Open-label Study to Evaluate Safety and Toxicity of Intravesical Instillation of TARA-002 in Adults with High-grade Non-muscle Invasive Bladder Cancer

This study is open-label dose expansion study to investigate the safety and toxicity of intravesical treatment of high-grade NMIBC (HGTa or CIS, including CIS with concomitant Ta) after transurethral resection of bladder tumor (TURBT) and/or biopsy using TARA-002 in adults unable to obtain intravesical Bacillus Calmette-Guérin (BCG), adults who have received at least one dose of intravesical BCG or adults who have received at least one dose of intravesical chemotherapy.

After completion of the dose escalation phase (Phase 1a) and after the RP2D has been established, the dose expansion phase (Phase 1b) will start enrollment of subjects with CIS NMIBC with active disease to further evaluate the safety and preliminary efficacy of TARA-002, at the established RP2D. CIS NMIBC with active disease is defined as disease present at the last cystoscopic evaluation prior to signing the ICF. Subjects enrolled in the dose expansion phase will not include subjects previously enrolled and treated in the dose escalation phase.

All subjects will receive 6 weeks of treatment at the established RP2D.

Study Overview

• Status: Completed
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Biological: TARA-002

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • USC Norris Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center (TMC) - Clinic/Outpatient Facility
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Poughkeepsie, New York, United States, 12603
      • Premier Medical Group of the Hudson Valley
    • Rochester, New York, United States, 14642
      • University of Rochester, Department of Urology
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates PC
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subjects 18 years of age or older at the time of signing the informed consent
• Subjects who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
• Subjects with a histologically confirmed, high-grade Ta or CIS (including CIS with concomitant Ta) urothelial cell carcinoma of the bladder according to central review
• Subjects who are treatment naïve, unable to obtain intravesical BCG for the treatment of NMIBC, have received at least one dose of intravesical BCG, or at least one dose of intravesical chemotherapy

Exclusion Criteria:

• Penicillin allergy (subjects with a questionable history of allergy to penicillin or no history of penicillin use will undergo penicillin allergy testing prior to inclusion in the study)
• Predominant (defined as > 50%) adenocarcinoma, squamous cell carcinoma, or histological variants including plasmacytoid, sarcomatoid, or squamous components according to central review
• Concomitant prostatic or upper tract urothelial involvement per Investigator's assessment
• Nodal involvement or metastatic disease that existed at any time (past or present disease)
• Bladder cancer stage ≥ T1 within the last 36 months according to central histology review
• Bladder cancer stage CIS with concomitant T1

For more information on eligibility criteria, please contact the sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TARA-002; TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin.	Biological: TARA-002; Phase 1b, Dose Expansion Phase: All subjects will receive 6 weekly doses of TARA-002 at the recommended Phase 2 dose (R2PD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b, Dose Expansion Phase: Incidence of AEs in subjects with CIS NMIBC with active disease	AE = adverse event	Day 1 to Day 78

Collaborators and Investigators

• Sponsor: Protara Therapeutics
• Investigators: Study Director: Chief Scientific Operations Officer, Protara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2023
• Primary Completion (Actual): September 12, 2024
• Study Completion (Actual): September 12, 2024

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: bladder cancer; Non-muscle invasive bladder cancer; carcinoma in situ; high grade Ta; high-grade NMIBC
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms
• Other Study ID Numbers: TARA-002-101(Phase 1b)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No