NMIBCPhase 1PARADIGM-1NCT06181266
A Phase 1/1b Study of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
A Phase 1 study testing ZH9 in people with NMIBC and High Risk NMIBC, run by Prokarium Ltd at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- NMIBC, High Risk NMIBC, Non Muscle Invasive Bladder Cancer
- What is being tested?
- ZH9
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesUnited States
- Study dates
- 8 Jan 2024to 5 Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Michael G. Oefelein Clinical Trials
Bakersfield, California, 93301
Duke Health-Duke Cancer Center
Durham, North Carolina, 27710
Carolina Urologic Research Center, LLC
Myrtle Beach, South Carolina, 29572
Urology San Antonio Medical Center
San Antonio, Texas, 78229
About this study
Official title: 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.
- Conditions
- NMIBC, High Risk NMIBC, Non Muscle Invasive Bladder Cancer
- Being tested
- ZH9
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZH9Drug
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 - ZH9 | Experimental | 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 Receives: Drug: ZH9 |
| Dose Level 2 - ZH9 | Experimental | 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 Receives: Drug: ZH9 |
| Dose Level 3 - ZH9 | Experimental | 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 Receives: Drug: ZH9 |
| Dose Level 4 - ZH9 | Experimental | 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 Receives: Drug: ZH9 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities
Toxicity will be evaluated according to the NCI CTCAE Version 5.0
Measured: 28 days
Secondary outcomes (7)
Rate of complete pathologic response
Rate of complete pathologic response at determined timepoints by cystoscopy, urine cytology, and if needed for pathological confirmation, biopsy
Measured: 3, 6, and 12 months
Rate of recurrence-free survival and duration or response
Rate of recurrence-free survival and duration of response as determined by cystoscopy and urine cytology
Measured: 3, 6, and 12 months
Rate of CR
Rate of CR as determined by biopsy in patients with CIS at baseline
Measured: 6 and 12 months
Proportion of patients with cystectomy-free survival
Proportion of patients with cystectomy-free survival as determined by cystoscopy and urine cytology
Measured: 6 and 12 months
Rate of progression-free survival
Rate of progression-free survival, including disease progression and all-cause death
Measured: 12 months
Overall response rate and recurrence-free rate
Overall response rate and recurrence-free rate in the bladder following IVI
Measured: 6 and 12 months
Change from baseline in systemic and local inflammatory markers in the bladder
Change from baseline in systemic and local inflammatory markers in the bladder as defined by clinical laboratory safety assessments (serum chemistry, hematology, urinalysis)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2023
- Study start8 Jan 2024
- Primary completion30 Aug 2025
- Study completion5 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NMIBCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- In Part 1, the safety, tolerability, and pharmacology of ZH9 administered as an IVI will be evaluated in a single ascending dose cohort in patients with NMIBC. Part 1 may examine up to 4 dose levels. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 cohorts in patients with NMIBC at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 (oral prime and IVI) will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prokarium Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Josefin-Beate Holz, MD, Study director, Prokarium Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06181266
- Sponsor's protocol ID
- PRK-23101
- Acronym
- PARADIGM-1
- Status last verified
- Oct 2026
- First submitted
- 12 Dec 2023
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Study Evaluating the Safety, Pharmacology, and Clinical Effect of ZH9 Treatment in Patients With Non-Muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT06181266
- Acronym / sponsor ID
- PARADIGM-1 / PRK-23101
- Conditions
- NMIBC, High Risk NMIBC, Non Muscle Invasive Bladder Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Prokarium LtdIndustry (pharma, biotech, devices)
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- 30 Aug 2025 (actual)
- Study completion
- 5 Aug 2026 (actual)
- First posted
- 26 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- In Part 1, the safety, tolerability, and pharmacology of ZH9 administered as an IVI will be evaluated in a single ascending dose cohort in patients with NMIBC. Part 1 may examine up to 4 dose levels. In Part 2, the safety, tolerability, and pharmacology of ZH9 oral prime followed by ZH9 IVI will be evaluated in 2 cohorts in patients with NMIBC at the doses and schedule established in Part 1. In Part 3, the safety, pharmacology, and clinical efficacy of ZH9 (oral prime and IVI) will be further evaluated in 2 expansion cohorts of patients with recurrent intermediate- and high-risk NMIBC.
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 - ZH9 | Experimental | Drug: ZH9Part 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 |
| Dose Level 2 - ZH9 | Experimental | Drug: ZH9Part 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 |
| Dose Level 3 - ZH9 | Experimental | Drug: ZH9Part 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 |
| Dose Level 4 - ZH9 | Experimental | Drug: ZH9Part 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 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZH9ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ΔaroC ΔssaV]), a differentiated novel microbial immunotherapy. | Drug | Dose Level 1 - ZH9, Dose Level 2 - ZH9, Dose Level 3 - ZH9, Dose Level 4 - ZH9 |
Primary outcome
Incidence of dose-limiting toxicities
Time frame: 28 days
Toxicity will be evaluated according to the NCI CTCAE Version 5.0
7 secondary outcomes
Rate of complete pathologic response
Time frame: 3, 6, and 12 months
Rate of recurrence-free survival and duration or response
Time frame: 3, 6, and 12 months
Rate of CR
Time frame: 6 and 12 months
Proportion of patients with cystectomy-free survival
Time frame: 6 and 12 months
Rate of progression-free survival
Time frame: 12 months
Overall response rate and recurrence-free rate
Time frame: 6 and 12 months
Change from baseline in systemic and local inflammatory markers in the bladder
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josefin-Beate Holz, MD study director
Prokarium Ltd
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZH9 in people with NMIBC and High Risk NMIBC, run by Prokarium Ltd at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.