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

August 16, 2025 updated by: Prokarium Ltd

A Phase 1/1b Study Evaluating the Safety, Pharmacology, and Clinical Effect 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Bakersfield, California, United States, 93301
        • Michael G. Oefelein Clinical Trials
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Health-Duke Cancer Center
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Carolina Urologic Research Center, LLC
    • Texas
      • San Antonio, Texas, United States, 78229
        • Urology San Antonio Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Level 1 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
Drug: ZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.
Experimental: Dose Level 2 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
Drug: ZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.
Experimental: Dose Level 3 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
Drug: ZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.
Experimental: Dose Level 4 - ZH9
Part 1 will evaluate SAD of ZH9 administered as an IVI in patients with recurrent NMIBC. A standard 3+3 escalation design will be employed with the dose levels
Drug: ZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities
Time Frame: 28 days
Toxicity will be evaluated according to the NCI CTCAE Version 5.0
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
3, 6, and 12 months
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, 6, and 12 months
Rate of CR
Time Frame: 6 and 12 months
Rate of CR as determined by biopsy in patients with CIS at baseline
6 and 12 months
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
6 and 12 months
Rate of progression-free survival
Time Frame: 12 months
Rate of progression-free survival, including disease progression and all-cause death
12 months
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
6 and 12 months
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)
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Prokarium Ltd

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Josefin-Beate Holz, MD, Prokarium Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 8, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 12, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 26, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRK-23101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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