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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)
• Intervention / Treatment: Drug: RAG-01

Detailed Description

This study includes a dose escalation and a dose expansion. The dose escalation part will adopt a '3+3' dose escalation design. Additional subjects may be enrolled to have approximately 12 patients in each selected dose level for RDE determination. A randomized, open label, parallel-arm study will be conducted during the dose expansion part for further dose exploration. Approximately 40-60 subjects will be randomized in a 1:1 ratio into two treatment groups with dose levels selected from dose escalation part of the study. Randomization will be stratified based on disease type at enrollment (papillary-only vs. CIS). A dose selection analysis will be performed to assess safety, efficacy, PK, and PD, where applicable, to determine the optimal dose for RAG-01. The main study period includes the screening, initial treatment and DLT assessment period, second and third treatment period and the sequential follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Long-Cheng Li; Phone Number: +86 18051622388; Email: lilc@ractigen.com

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Genesiscare North Shore
      • Contact: Laurence Krieger, MBCHB; Phone Number: +61 2 8037 4100; Email: laurence_krieger@hotmail.com
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Recruiting
      • The Royal Melbourne Hospital
      • Contact: Paul Anderson, MBBS FRACS; Phone Number: 0393427294; Email: mr.paul.anderson@gmail.com
    • Melbourne, Victoria, Australia, 3199
      • Recruiting
      • Peninsula & South Eastern Haematology and Oncology Group
      • Contact: Sanjeev Sewak, MBBS, ECFMG; Phone Number: 0397815244; Email: sewaks01@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to understand the study and have signed the informed consent form;
2. Any adult ≥ 18 years old;
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAG-01 dose escalation and dose expansion; The starting dose of RAG-01 is 30mg, and there are 4 dose cohorts, including 30mg, 100mg, 300mg, 600mg, respectively. Each eligible subject will be distributed into one cohort. Safety and pharmacokinetics are assessed at each dose level.	Drug: RAG-01; RAG-01 is a therapeutic small activating RNA (saRNA) duplex molecule comprised of two partially chemically modified complementary oligonucleotide strands.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of RAG-01	Dose-limiting toxicity (DLT)	Within 21 days after first instillation

Collaborators and Investigators

• Sponsor: Ractigen Therapeutics.
• Investigators: Principal Investigator: Laurence Krieger, MBCHB, GenesisCare, 7 Westbourne Street, St Leonards, NSW 2065, Australia

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms
• Other Study ID Numbers: RAG-01-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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