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NCT Number: NCT06181266

A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer

This is a first-in-human, multicenter, Phase 1/1b, 3-part, double-blind study of ZH9 in patients with recurrent NMIBC who are eligible for intravesical therapy. In Part 1, the safety, tolerability, and pharmacology of ZH9 IVI will be evaluated in a single ascending dose (SAD) patient cohort. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 patient cohorts at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

NMIBC Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications High Risk NMIBC Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Non Muscle Invasive Bladder Cancer Non-Muscle Invasive Bladder Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Michael G. Oefelein Clinical Trials, Bakersfield, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 18 years
  • Histologically documented recurrence of NMIBC
  • BCG unresponsive (BCG naïve patients may be enrolled if they have received at least 1 line of adequate intravesical standard of care (SOC) treatment and are either not candidates for BCG or do not have access to BCG (e.g., BCG shortage))
  • Eastern Cooperative Oncology Group Performance Status 0-1
  • Adequate organ and marrow function
  • Highly effective contraception if risk of conception exists.
  • A female participant is eligible if not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP) or is a WOCBP that uses highly effective contraception.

Exclusion criteria

  • Received treatment with any local or systemic antineoplastic therapy within 3 weeks or 5× the plasma half-life prior to first dose of ZH9
  • Major surgery or radiation within the 3 weeks prior to Screening (TURBT is not considered major surgery)
  • Concurrent urinary tract infection or history of clinically significant polyuria
  • Symptoms consistent with typhoid
  • Evidence of infection within 2 weeks of the first dose of ZH9
  • Significant 12-lead electrocardiogram abnormalities
  • History of malignancy within the previous 12 months
  • History of allogeneic tissue/solid organ transplant

Treatment and study plan

ZH9

Drug

ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.

Primary outcomes

  1. Incidence of dose-limiting toxicities

    Time frame: 28 days

    Toxicity will be evaluated according to the NCI CTCAE Version 5.0

Secondary outcomes

  1. Rate of complete pathologic response

    Time frame: 3, 6, and 12 months

    Rate of complete pathologic response at determined timepoints by cystoscopy, urine cytology, and if needed for pathological confirmation, biopsy

  2. Rate of recurrence-free survival and duration or response

    Time frame: 3, 6, and 12 months

    Rate of recurrence-free survival and duration of response as determined by cystoscopy and urine cytology

  3. Rate of CR

    Time frame: 6 and 12 months

    Rate of CR as determined by biopsy in patients with CIS at baseline

  4. Proportion of patients with cystectomy-free survival

    Time frame: 6 and 12 months

    Proportion of patients with cystectomy-free survival as determined by cystoscopy and urine cytology

  5. Rate of progression-free survival

    Time frame: 12 months

    Rate of progression-free survival, including disease progression and all-cause death

  6. Overall response rate and recurrence-free rate

    Time frame: 6 and 12 months

    Overall response rate and recurrence-free rate in the bladder following IVI

  7. Change from baseline in systemic and local inflammatory markers in the bladder

    Time frame: 12 months

    Change from baseline in systemic and local inflammatory markers in the bladder as defined by clinical laboratory safety assessments (serum chemistry, hematology, urinalysis)

Sponsors and collaborators

Lead sponsor

Prokarium Ltd

Industry

Registry information

Official study title

A Phase 1/1b Study Evaluating the Safety, Pharmacology, and Clinical Effect of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer

Acronym: PARADIGM-1

Important dates

Study start
2024
Primary completion
2025
Study completion
2027
First posted
Dec 26, 2023
Registry last updated
Aug 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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