A Study in Subjects With Human Papillomavirus 16 or 18 Associated Cervical Intraepithelial Neoplasia Grade 2 or 3

NCT06273553 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: RG002-A1201
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

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).

Conditions

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

Keywords

HPV 16 or 18; mRNA vaccine; CIN 2; CIN 3

Outcome Measures

Primary Outcomes (3)

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

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

  Week 9

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

  MTD:Week 9; RP2D: Week 36

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

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

  Week36

Secondary Outcomes (15)

• Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with histopathological regression

  Week36

• Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with clearance of HPV16/18

  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 level of cellular immune response

  Week36

• Part A and B: Immunogenicity of RG002 Injection,measured by the proportion of T lymphocytes

  Week36

Study Arms (1)

RG002 Injection

EXPERIMENTAL

In Part A, subjects with histologically confirmed Cervical Intraepithelial Neoplasia Grade 2 or 3 (CIN2/3) associated with Human Papillomavirus (HPV) 16 or 18, will be allocated to three dose cohorts that are 25µg,75µg and 150µg. In Part B, subjects with histologically confirmed Cervical Intraepithelial Neoplasia Grade 2 or 3 (CIN2/3) associated with Human Papillomavirus (HPV) 16 or 18, will be allocated to 1 or 2 dose levels according to the results of Part A. All subjects will receive a total of three RG002 Injections, administered intramuscularly at assigned dose level, with a dosing frequency of every 2 weeks (D1, D15, and D29).

Biological: RG002 injection

Interventions

RG002 injection BIOLOGICAL

In Part A, there are three dose cohorts that are 25µg,75µg and 150µg. In Part B, there will 1 or 2 dose levels according to the results of Part A. All subjects will receive a total of three RG002 Injections, administered intramuscularly at assigned dose level, with a dosing frequency of every 2 weeks (D1, D15, and D29).

RG002 Injection

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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/m2.
• 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).
• Hepatic function: total bilirubin ≤ 1.5 × ULN, Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤ 1.5 × ULN.
• Women of child-bearing potential (WOCBP) agree to remain sexually abstinent, use medically effective contraception (i.e., complex contraception, male condom and spermicide, contraceptive patches, barrier methods, spermicide, etc.), from enrollment to 9 months after the last injection or have a partner who is sterile (i.e., vasectomy).
• Able and willing to comply with all study procedures.

You may not qualify if:

• 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.
• Female subjects in pregnancy or lactation, or a positive result on a serum human chorionic gonadotropin (HCG) test at screening (Visit 1) or a positive urine pregnancy test pre-vaccination at Visit 2 (and at subsequent vaccination visits).
• Currently receiving or has received treatment with systemic steroids in the following dosages prior to administration of the first study vaccination.
• Long-term corticosteroids: ≥0.5 mg/kg/day of oral prednisolone or equivalent, within 30 days prior to administration of the first study vaccination.
• Sporadic corticosteroids: ≥1 mg/kg/day of oral prednisolone or equivalent for 2 or more short courses of \> 3 days.
• Note: Current or recent use of eye drop or inhaled glucocorticoid therapy is acceptable.

Sponsors & Collaborators

• RinuaGene Biotechnology Co., Ltd.: lead

Related Publications (1)

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 RESULT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 22, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 22, 2024

Record last verified: 2024-02