AzTrials
AzTrials

Human Papillomavirus Associated Intraepithelial NeoplasiaPhase 1/2NCT06273553

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

A Phase 1/2 study testing RG002 injection in people with Human Papillomavirus Associated Intraepithelial Neoplasia and Cervical Intraepithelial Neoplasia Grade 2/3, run by RinuaGene Biotechnology Co., Ltd..

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 55 years, women only
What is being tested?
RG002 injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
No sites listed yet
Study dates
Mar 2024to Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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;
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Immunosuppression due to treatment for concurrent disease or medical history: HIV treatment, antirheumatic drugs, organ or bone marrow transplantation or relevant treatment.
  • Systemic treatment for malignancy within 2 years of enrollment.
  • Administration of any blood product within 3 months of enrollment.
  • Administration of any vaccine within 4 weeks of enrollment.
  • A history of any therapeutic HPV vaccination (commercially approved prophylactic HPV vaccination is acceptable).
  • Other condition or prior therapy that, in the opinion of the investigator, compromises the subject's welfare or may confound study results.
  • Tattoos, scars, or active lesions/rashes within 2 cm of the intended site of vaccination (deltoid muscle) or any implantable leads, that may affect the safety observation.
  • Adverse events that do not recover to grade 1 during the screening period.
  • Subjects are currently participating or has participated in a study with an investigational drug or device within 30 days of signing informed consent.
  • Subjects who are judged by the investigator to have a history of other serious systemic diseases, or not suitable for participating in the trial for any other reason (the subject has mental illness, alcohol abuse, drug use or drug abuse that may affect her compliance with the trial or may interfere with the interpretation of the study results).

About this study

Official title: 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)

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).

Being tested
RG002 injection
Keywords
HPV 16 or 18, mRNA vaccine, CIN 2, CIN 3

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RG002 injectionBiological

    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).

Study groups in NCT06273553
Study groupRoleWhat they receive
RG002 InjectionExperimentalIn 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).
Receives: Biological: RG002 injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Week 9

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

    Measured: MTD:Week 9; RP2D: Week 36

  3. 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

    Measured: Week36

Secondary outcomes (15)

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

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

    Measured: Week36

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

    The clearance of HPV16 or HPV18 will be evaluated according to the results of HPV test at Week 21 and Week 36.

    Measured: Week36

  3. Part A: Preliminary efficacy of RG002 Injection,measured by proportion of subjects with histopathological regression and clearance of HPV16/18

    The proportion of subjects with histopathological regression to CIN1 or normal and clearance of HPV16 or HPV18, or both at Week36.

    Measured: Week36

  4. Part A and B: Immunogenicity of RG002 Injection,measured by the level of cellular immune response

    The level of cellular immune response in Peripheral blood mononuclear cells (PBMCs) as measured by IFN-γ enzyme-linked immunosorbent spot-forming (ELISpot) assay

    Measured: Week36

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

    The immuno-phenotyping including the proportion of CD3+CD4+CD137+ and CD3+CD8+CD137+ T lymphocytes in whole blood as measured by flow cytometry.

    Measured: Week36

  6. Part A and B: Immunogenicity of RG002 Injection,measured by the expression of cytokines in serum

    The expression of cytokines in serum, i.e., IL-1β, IL-1ra, IL-2, IL-6, IL-10, GM-CSF, TNF-α and IFN-γ measured by MSD® Assays.

    Measured: Week36

  7. Part A and B: Immunogenicity of RG002 Injection,measured by the serum levels of anti-HPV16 and anti-HPV18 IgG antibodies.

    Serum levels of anti-HPV16 and anti-HPV18 IgG antibodies as measured by Luminex.

    Measured: Week36

  8. Part A and B: Exposure level of RG002 Injection, measured by mRNA

    The plasma exposure level(AUC, Cmax, etc.) of mRNA will be measured Real Time Quantitative-Polymerase Chain Reaction (RT-qPCR)

    Measured: Week7

  9. Part A and B: Exposure level of RG002 Injection, measured by cationic lipids

    The plasma exposure level(AUC, Cmax, etc.) of cationic lipids will be measured by Liquid Chromatography Tandem Mass Spectrometry(LC-MS/MS).

    Measured: Week7

  10. 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

    The serum titer of anti-PEG IgG and anti-PEG IgM as measured by enzyme-linked immunosorbent assay (ELISA).

    Measured: Week6

  11. Part B: Secondary efficacy, measured by proportion of subjects with histopathological regression

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

    Measured: Week36

  12. Part B: Secondary efficacy, measured by proportion of subjects with clearance of HPV16/18

    The clearance of HPV16 or HPV18 will be evaluated according to the results of HPV test at Week 21 and Week 36.

    Measured: Week36

  13. Part B: Secondary efficacy, measured by proportion of subjects with histopathological regression and clearance of HPV16/18

    The proportion of subjects with histopathological regression to CIN1 or normal and clearance of HPV16 or HPV18, or both at Week36.

    Measured: Week36

  14. Part B: 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

    Measured: Week9

  15. 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.

    The level of potential biomarkers of RG002 Injection, i.e., CD45, CD3, CD4, CD8, CD25, FOXP3, PD-1, and CD137, and the level of infiltrating T cells (CD3, CD8, FOXP3, TIM3, Tbet, PD-1, DAPI) and myeloid cells (CD14, CD33, CD68, CD163, CD11c, PD-L1, DAPI) in the lesions.

    Measured: Week36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2024
  2. Study startMar 2024 (estimated)
  3. Primary completionOct 2026 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06273553
Sponsor's protocol ID
RG002-A1201
Status last verified
Feb 2024
First submitted
31 Jan 2024
Last updated
22 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 33538338

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RG002 injection in people with Human Papillomavirus Associated Intraepithelial Neoplasia and Cervical Intraepithelial Neoplasia Grade 2/3, run by RinuaGene Biotechnology Co., Ltd..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Safety and Tolerability of RG002 Injection, measured by the incidence of adverse events (time frame: Week 9). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06273553, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in