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

Non Muscle Invasive Bladder Cancer Clinical Trial

— PARADIGM-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06181266
• Other study ID #: PRK-23101
• Status: Recruiting
• Phase: Phase 1
• Start date: January 8, 2024
• Est. completion date: May 30, 2027

Study information

• Verified date: November 2023
• Source: Prokarium Ltd
• Contact: Melinda Snyder
• Phone: 6172334057
• Email: melinda.snyder[@]prokarium.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: May 30, 2027
• Est. primary completion date: February 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• NMIBC
• Non Muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• ZH9
ZH9 is a live attenuated S. enterica serovar Typhi ZH9 [Ty2 ?aroC ?ssaV]), a differentiated novel microbial immunotherapy.

Locations

Country	Name	City	State
United States	Chesapeake Urology	Hanover	Maryland
United States	Carolina Urologic Research Center, LLC	Myrtle Beach	South Carolina
United States	Urology San Antonio Medical Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Prokarium Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities	Toxicity will be evaluated according to the NCI CTCAE Version 5.0	28 days
Secondary	Rate of complete pathologic response	Rate of complete pathologic response at determined timepoints by cystoscopy, urine cytology, and if needed for pathological confirmation, biopsy	3, 6, and 12 months
Secondary	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	3, 6, and 12 months
Secondary	Rate of CR	Rate of CR as determined by biopsy in patients with CIS at baseline	6 and 12 months
Secondary	Proportion of patients with cystectomy-free survival	Proportion of patients with cystectomy-free survival as determined by cystoscopy and urine cytology	6 and 12 months
Secondary	Rate of progression-free survival	Rate of progression-free survival, including disease progression and all-cause death	12 months
Secondary	Overall response rate and recurrence-free rate	Overall response rate and recurrence-free rate in the bladder following IVI	6 and 12 months
Secondary	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)	12 months