A Study of RAG-01 in Patients With Non-muscle-invasive Bladder Cancer (NMIBC) Who Have Failed Bacillus Calmette Guérin (BCG) Therapy

Non-Muscle-Invasive Bladder Cancer (NMIBC) Clinical Trial

Official title:

A Phase Ⅰ, Open Label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of RAG-01 in Patients With Non-muscle-invasive Bladder Cancer (NMIBC) Who Have Failed Bacillus Calmette Guérin (BCG) Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06351904
• Other study ID #: RAG-01-01
• Status: Recruiting
• Phase: Phase 1
• Start date: April 3, 2024
• Est. completion date: August 31, 2025

Study information

• Verified date: April 2024
• Source: Ractigen Therapeutics.
• Contact: Long-Cheng Li
• Phone: +86 18051622388
• Email: lilc[@]ractigen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of RAG-01 in patients with NMIBC who have failed BCG therapy.

Description:

The study is planned to include a "3+3" dose escalation phase. The primary study period includes a screening period, a treatment and Dose-Limiting Toxicity (DLT) assessment period, and a follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: August 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Ability to understand the study and have signed the informed consent form;

2. = 18, = 75 years old, male or female;

3. Pathologically confirmed high grade NMIBC defined as grade 2 or grade 3 disease;

4. Expected survival = 6 months;

5. ECOG PS =2;

6. Sufficient organ functions, as defined below:

Investigations Hematology Absolute Neutrophil Count (ANC): = 1.5 x 109/L Hemoglobin: = 90 g/L Platelet: = 100 x 109/L Liver Function Serum bilirubin: = 1.25×ULN or 2.5×ULN(with Gilbert syndrome) AST & ALT: = 2.5×ULN Renal Function Creatinine Clearance (Cockcroft-Gault equation): = 30 mL/min

7. Subject must be able to tolerate catheterization;

8. Female subject of childbearing potential and her spouse must use adopt effective contraception (non-pharmacological contraception required) from signing informed consent to within 6 months after the last instillation.

Exclusion Criteria:

1. Subject who is allergy to RAG-01 or similar products;

2. Except for TURBT, the subject received other anti-tumor treatments, and the last administration date is within = 21 days or 5 half-lifes whichever is shorter from the date of signing ICF;

3. Subject with imaging examination diagnosed extravesical metastasis, including ureter and urethra;

4. Subject has other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable;

5. The following illnesses have not been relieved to CTCAE 0-1:

1. Uncontrolled acute and chronic infections, such as pneumonia, biliary tract infection, hepatitis B virus infection and hepatitis C virus infection;

2. Dyspnea;

3. Acute and chronic kidney injury, and inflammation;

4. Urinary incontinence;

5. Urinary frequency;

6. Urinary tract obstruction (except benign prostatic hypertrophy);

6. Subject could not hold the urine for at least 90 mins due to any reason;

7. New York Heart Association (NYHA) 3 or 4 grade;

8. Coronary heart disease related symptoms have not been relieved to CTCAE 0-1, including: myocardial infarction, unstable angina pectoris, congestive heart failure and arrhythmia;

9. Subject with QTc >470 msec.

10. Cerebrovascular accidents have not been relieved to CTCAE 0-1;

11. HIV positive; Active hepatitis B or C. For active HBV, it's defined as HBsAg positive with HBV DNA = ULN, for active HCV, it's defined as HCV antibody positive with HCV RNA = ULN, respectively.

12. Subject is pregnant or lactating during the treatment period;

13. History of central nervous system or psychiatric disorders, e.g., epilepsy or dementia;

14. Other severe systemic diseases which might compromise the subject's compliance to the study, e.g., uncontrolled diabetes, gastrointestinal disorders, and renal diseases;

15. Any other situations which are judged by the investigator, would exposure the subject to unnecessary risk, therefore he/she is not eligible.

Related Conditions & MeSH terms

• Non-Muscle-Invasive Bladder Cancer (NMIBC)
• Urinary Bladder Neoplasms

Intervention

Drug:
• RAG-01
RAG-01 is a therapeutic small activating RNA (saRNA).

Locations

Country	Name	City	State
Australia	GenesisCare North Shore	St Leonards	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Ractigen Therapeutics.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of RAG-01 in patients with non-muscle-invasive bladder cancer (NMIBC)	Adverse events (AEs), serious adverse events (SAEs), and adverse events during treatment (TEAEs)	From the screening to 6 months after the first instillation of RAG-01
Primary	Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of RAG-01	Dose-limiting toxicity (DLT)	Within 21 days after first instillation