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

Phase 1

Recruiting

• Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)
• Interventions: Drug: RAG-01

• Registration Number: NCT06351904
• Lead Sponsor: Ractigen Therapeutics.

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-04-02
• Study First Submitted QC: 2024-04-02
• Study Start: 2024-04-03
• Study First Posted: 2024-04-08
• Status Verified: 2024-06
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Primary Completion: 2025-06-30
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAG-01	RAG-01	The starting dose of RAG-01 is 30 mg, and there are 4 dose cohorts, including 30 mg, 100 mg, 300 mg and 600 mg, respectively. Each eligible subject will be distributed into one dose cohort.

Primary Outcome Measures

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

Trial Locations

Locations (3)

The Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Peninsula & South Eastern Haematology and Oncology Group; 🇦🇺 Melbourne, Victoria, Australia

GenesisCare North Shore; 🇦🇺 St Leonards, New South Wales, Australia