Application of mRNA Immunotherapy Technology in Hepatitis B Virus-related Refractory Hepatocellular Carcinoma

February 12, 2023 updated by: Xingchen Peng, West China Hospital

A Phase I Study of mRNA Vaccine for Patients With HBV-positive Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the efficacy and safety of mRNA vaccine for HBV-positive Advanced Hepatocellular Carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma is a common malignant tumor of the digestive system worldwide and is particularly prevalent in China. More than 80% of hepatocellular carcinoma patients in China have concomitant hepatitis B virus infection. However, there are limited effective treatments for hepatocellular carcinoma that have failed standard treatment, and the prognosis for these patients is poor. About 350 million people worldwide are chronically infected with the hepatitis B virus (HBV), and chronic HBV infection accounts for at least 50% of hepatocellular carcinoma cases worldwide. Therefore, anti-HBV can be a potential target for hepatocellular carcinoma.

The mRNA vaccines are a highly promising novel anti-tumor approach. The applicant team of this project has carried out research on raw materials and preparation process, vaccine stability, quality standard, delivery vector construction, and anti-tumor mechanism of action of mRNA immune formulation in the early stage. Now we have completed the optimized design of mRNA raw materials, and the construction and optimization of the mRNA delivery vector. The tumor therapeutic mRNA immune formulation with high efficiency, safety, scalable preparation, and quality control has been selected and preclinical evaluation has been completed to verify its safety and efficacy. The project has constructed mRNA vaccines, and no similar therapeutic method or product has been reported in the international arena.

This project proposes to conduct a phase I clinical study based on the previous study to include patients with advanced hepatocellular carcinoma who have failed second-line standard treatment or cannot receive standard treatment. A dose-escalation trial will be conducted, and one effective dose will be selected for a fixed-dose trial to explore the safety, tolerability, and efficacy of mRNA immunotherapy technology for clinical application. Project implementation is expected to benefit a wide range of hepatocellular carcinoma patients and improve their prognosis.

Study Type

Interventional

Enrollment (Anticipated)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients: ≥ 18 years old; ≤ 70 years old;
  2. Patients with HBV-positive advanced hepatocellular carcinoma after failure of second-line standard therapy (including PD-1 inhibitor therapy, chemotherapy, and anti-vascular targeted drugs);
  3. HBsAg positive, regardless of whether the peripheral blood is positive for HBV DNA.
  4. ECOG physical fitness score: 0~1 points;
  5. Estimated survival ≥ 3 months;

  6. The main organs have good function, that is, the relevant examination indicators within random 14 days meet the following requirements:

    1. Blood routine examination: hemoglobin ≥ 80 g/L (no blood transfusion within 14 days); Neutrophil count> 1.5×109/L; Platelet count≥ 80×109/L;

    2. Biochemical examination: total bilirubin ≤ 1.5× ULN (upper limit of normal); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN; If liver metastases are present, ALT or AST ≤ 5×ULN; Endogenous creatinine clearance

      ≥ 60 ml/min (Cockcroft-Gault formula);

    3. Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥50%.
  7. Sign the informed consent form;
  8. Good compliance, family members agree to cooperate with survival follow-up.

Exclusion Criteria:

  1. Participated in clinical trials of other drugs within 4 weeks;
  2. The patient has a history of other tumors, unless it is cervical cancer in situ, treated cutaneous squamous cell carcinoma or bladder epithelial tumor or other malignant tumors that has received radical treatment (at least 5 years before enrollment)
  3. Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure above NYHA grade 2, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
  4. For female subjects: pregnant or lactating women.
  5. The patient has active tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTC, 3rd edition); There is HIV infection with active HBV infection, HCV infection.
  6. Those who have a history of psychotropic drug abuse and have mental disorders that cannot be remitted;
  7. The subject has any active autoimmune disease or has a history of autoimmune disease (such as, but not limited to uveitis, enteritis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; Participants with vitiligo or who had complete remission of asthma in childhood and did not require any intervention in adulthood could be included; Participants in asthma requiring medical intervention with bronchodilators omitted).
  8. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the patient's research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Cohort
With 20ug as the starting point, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose, and the intramuscular injection was administered again every 7 days, and after 4 doses, the 5th dose was given after 1-month interval.
Biological: HBV mRNA vaccine
With 20ug as the starting point, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose, and the intramuscular injection was administered again every 7 days, and after 4 doses, the 5th dose was given after 1-month interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: up to 12 months
Adverse events defined as the number of participants with adverse events according
up to 12 months
Objective response rate
Time Frame: up to 12 months
ORR is defined as the percentage of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more)
up to 12 months
Progress-Free Survival
Time Frame: up to 12 months
PFS is defined as the time from the administration of the first dose to first disease
up to 12 months
Overall Survival
Time Frame: up to 12 months]
OS is defined as the time from the administration of the first dose to death
up to 12 months]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Investigators

  • Principal Investigator: Xingchen Peng, West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 15, 2023

Primary Completion (Anticipated)

January 1, 2024

Study Completion (Anticipated)

January 1, 2025

Study Registration Dates

First Submitted

January 30, 2023

First Submitted That Met QC Criteria

February 12, 2023

First Posted (Estimate)

February 22, 2023

Study Record Updates

Last Update Posted (Estimate)

February 22, 2023

Last Update Submitted That Met QC Criteria

February 12, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-1371

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma

Clinical Trials on HBV mRNA vaccine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Thailand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe