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

NCT ID: NCT06351904

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-03
• Study Completion Date: 2028-08-31

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

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.

Conditions

Non-Muscle-Invasive Bladder Cancer (NMIBC)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RAG-01

Intervention Type: DRUG

RAG-01 is a therapeutic small activating RNA (saRNA) duplex molecule comprised of two partially chemically modified complementary oligonucleotide strands.

Interventions

RAG-01

RAG-01 is a therapeutic small activating RNA (saRNA) duplex molecule comprised of two partially chemically modified complementary oligonucleotide strands.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ractigen Therapeutics.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurence Krieger, MBCHB

Role: PRINCIPAL_INVESTIGATOR

GenesisCare, 7 Westbourne Street, St Leonards, NSW 2065, Australia

Locations

GenesisCare North Shore

St Leonards, New South Wales, Australia

Site Status: RECRUITING

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status: RECRUITING

Peninsula & South Eastern Haematology and Oncology Group

Melbourne, Victoria, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Long-Cheng Li

Role: CONTACT

lilc@ractigen.com

+86 18051622388

Facility Contacts

Laurence Krieger, MBCHB

Role: primary

laurence_krieger@hotmail.com

+61 2 8037 4100

Paul Anderson, MBBS FRACS

Role: primary

mr.paul.anderson@gmail.com

0393427294

Sanjeev Sewak, MBBS, ECFMG

Role: primary

sewaks01@yahoo.com

0397815244

Other Identifiers

RAG-01-01

Identifier Type: -

Identifier Source: org_study_id