An Open-Label, Phase 1/2 Study to Evaluate the Safety, Tolerability, Immunogenicity and Efficacy of RG002 Injection (an mRNA Therapeutic Vaccine) in Subjects With Human Papillomavirus (HPV) 16 or 18 Associated Cervical Intraepithelial Neoplasia Grade 2 or 3 (CIN2/3)

RinuaGene Biotechnology Co., Ltd.0 sites39 target enrollmentMarch 2024

ConditionsHuman Papillomavirus Associated Intraepithelial Neoplasia Cervical Intraepithelial Neoplasia Grade 2/3 Human Papillomavirus Type 16 Infection Human Papillomavirus Type 18 Infection

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Human Papillomavirus Associated Intraepithelial Neoplasia
Sponsor: RinuaGene Biotechnology Co., Ltd.
Enrollment: 39
Primary Endpoint: Part B: Primary efficacy of RG002 Injection, measured by the proportion of subjects with histopathological regression
Status: Not yet recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to to evaluate the safety, tolerability, immunogenicity, and efficacy of RG002 Injection in subjects with HPV16/18 associated Cervical Intraepithelial Neoplasia Grade 2 or 3(CIN2/3).

Registry

clinicaltrials.gov

Start Date

March 2024

End Date

December 2027

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

RinuaGene Biotechnology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent in accordance with study site guidelines.
•Female 18\~45 years of age when signing the ICF for Part A, and 18\~55 years of age when signing the ICF for Part B.
•Body mass index (BMI) ≤30 kg/m
•Pathological diagnosis of CIN Grade 2 or 3 as confirmed by central pathological reviewers within 12 weeks prior to administration of first study vaccination.
•The lesion of CIN Grade 2 or 3 is large enough for histopathologic biopsy at screening and during treatment.
•Has a satisfactory colposcopy at screening, i.e., the entire lesion as well as the entire squamocolumnar junction (type 1 or 2 transformation zone) is visualizable by colposcopy;
•Confirmed high-risk HPV infection with HPV16+ and / or HPV18+ by a commercially available high-risk DNA assay (e.g., Cobas® HPV test from Roche).
•Adequate hematologic, renal, and hepatic function are determined by the Investigator, based upon medical history, physical examination, and laboratory test results at screening:
•Bone marrow function: absolute neutrophil count ≥1,500/µL, hemoglobin (HGB) ≥ 9 g/dL, and platelets ≥ 100,000/ µL.
•Renal function: creatinine ≤ 1.5 × institutional upper limit of normal (ULN).

Exclusion Criteria

•Cervical adenocarcinoma in situ (AIS), or atypical endometrial or glandular cells, or evidence of invasive cervical carcinoma on cervical biopsy within 12 weeks prior to administration of first study vaccination.
•High-grade intraepithelial neoplasia or invasive carcinoma of vulva, vagina or anus.
•History of severe allergy to any vaccine or serious hypersensitivity reaction to a known ingredient (e.g., PEG) of RG002 injection judged by the investigator.
•Active infection with herpes simplex virus (HSV).
•Positive serological test at screening for HIV virus, active syphilis infection, or positive hepatitis B virus surface antigen (HbsAg) and the number of copies of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) at screening, or HbsAg (-), hepatitis B core antibody (HbcAb) (+) and the number of copies of HBV DNA ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) after treatment of HBV infection, or positive hepatitis C antibody (HCV-Ab) and hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ ULN of the study site.
•Subjects with a concurrent condition of fatty liver disease at screening.
•Subjects with poorly controlled diabetes (fasting blood glucose ≥ 10mmol/L) after drug treatment at screening.
•History of serious cardiovascular and cerebrovascular diseases, including but not limited to serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention; repeated 12-lead ECG with QTcF interval ≥ 470 msec; acute coronary syndrome, congestive cardiac failure, aortic dissection, stroke or other Grade 3 or above cardiovascular and cerebrovascular events within 6 months before the first administration; New York Heart Association (NYHA) cardiac function classification ≥ Grade III or hypertension that cannot be clinically controlled (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg).
•Major surgery (except for surgery for diagnostic purposes) within 4 weeks before the first administration or expected to undergo major surgery (except for surgery for diagnostic purposes) during the study period; If major surgery occurred \> 4 weeks prior to the first administration of the study, individual must have recovered adequately from the toxicity and/or complications from the intervention prior to the first administration of the study.
•Hereditary hemorrhagic tendency or coagulation dysfunction, or a history of thrombosis or hemorrhagic disease, or requirement of continuous use of anticoagulants.

Outcomes

Primary Outcomes

Part B: Primary efficacy of RG002 Injection, measured by the proportion of subjects with histopathological regression

Time Frame: Week36

The proportion of subjects with histopathological regression to either CIN1 or normal at Week 36

Part A: Safety and Tolerability of RG002 Injection, measured by the incidence of adverse events

Time Frame: Week 9

Safety and Tolerability of RG002 Injection will be measured by the incidence of adverse events per CTCAE v5.0

Part A: Maximum tolerated dose (MTD) and/or RP2D of RG002 Injection

Time Frame: MTD:Week 9; RP2D: Week 36

Secondary Outcomes

Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with histopathological regression(Week36)
Part A and B: Immunogenicity of RG002 Injection,measured by the level of cellular immune response(Week36)
Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with histopathological regression and clearance of HPV16/18(Week36)
Part A and B: Immunogenicity of RG002 Injection,measured by the expression of cytokines in serum(Week36)
Part A and B: Exposure level of RG002 Injection, measured by cationic lipids(Week7)
Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with clearance of HPV16/18(Week36)
Part A and B: Immunogenicity of RG002 Injection,measured by the serum levels of anti-HPV16 and anti-HPV18 IgG antibodies.(Week36)
Part B: Secondary efficacy, measured by proportion of subjects with histopathological regression and clearance of HPV16/18(Week36)
Part B: Safety and tolerability of RG002 Injection, measured by the incidence of adverse events(Week9)
Part A and B: Immunogenicity of RG002 Injection,measured by the proportion of T lymphocytes(Week36)
Part A and B: Anti-drug antibody (ADA) to polyethylene glycol (PEG) of RG002 injection, measured by the serum titer of anti-PEG IgG and anti-PEG IgM(Week6)
Part B: Secondary efficacy, measured by proportion of subjects with clearance of HPV16/18(Week36)
Part A and B: Exposure level of RG002 Injection, measured by mRNA(Week7)
Part B: Secondary efficacy, measured by proportion of subjects with histopathological regression(Week36)
Part B: Optionally assess the biomarker of RG002 Injection, measured by the level of potential biomarkers and the level of infiltrating T cells and myeloid cells in the lesions.(Week36)