Efficacy and Safety of Dual-plasmid Hepatitis B Virus DNA Vaccine in Chronic Hepatitis B Patients

NCT01487876 | Unknown Phase 2 DMC

• 1 other identifier: 2011005SW0101
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

In order to study the immunotherapeutic effects of electroporation (EP)-mediated dual-plasmids Hepatitis B Virus DNA vaccine, the investigators plan to conduct a double-blind, randomized, placebo-controlled trial, approved by Chinese State Food and Drug Administration with written informed consent from each chronic hepatitis B (CHB) patients with baseline ALT more than 2 times the ULN, for whom antiviral treatment is indicated and who were under the simultaneous lamivudine (LAM) chemotherapy.

Conditions

Chronic Hepatitis B

Keywords

DNA vaccine; HBV; Chronic hepatitis B (CHB); T-cell

Outcome Measures

Primary Outcomes (3)

• HBV DNA suppression

  Suppression of HBV DNA was defined as the \>2 log10 decrease of viral load from baseline level.

  Before and after DNA vaccine injection: weeks 0, 60.

• Loss of HBeAg

  HBeAg serum titer was dropped to the detection limit by quantitative determination.

  Weeks 0, 48.

• Appearance of Anti-HBe

  At weeks 0,48.

Secondary Outcomes (4)

• HBeAg seroconversion rate

  At weeks 0, 12, 24, 48, 72.

• The occurrence of YMDD mutants

  At weeks 0, 48, 72.

• Viral breakthrough rate

  At weeks 0, 12, 24, 40, 48, 56, 60, 64, 72.

• HBV Ag specific T cell immunity

  At weeks 0, 12, 24, 36, 52, 72.

Study Arms (2)

LAM+DNA vaccine

EXPERIMENTAL

lamivudine (LAM) chemotherapy and DNA vaccine

Biological: HBV DNA vaccine

LAM+Placebo

PLACEBO COMPARATOR

Each volunteer received 4 injections of 4 mg placebo scheduled by a prime and 3 boosts at intervals of 4, 8, 12 weeks. lamivudine (LAM) chemotherapy and Placebo

Other: Placebo

Interventions

HBV DNA vaccine BIOLOGICAL

HBV DNA vaccine means that each volunteer received 4 injections of 4 mg DNA vaccine scheduled by a prime and 3 boosts at intervals of 4, 8, 12 weeks.

LAM+DNA vaccine

Placebo OTHER

Placebo means the arm in which each volunteer received 4 injections of 4 mg placebo scheduled by a prime and 3 boosts at intervals of 4, 8, 12 weeks.

LAM+Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-65 years with either sex;
• HBV serology meet the following criteria:
• HBsAg-positive lasting for at least 6 months at the time of screening;
• HBeAg-positive at the time of screening;
• Serum HBV DNA≥1.0×10E5 copies/ml at the time of screening
• U/L\<ALT\<400U/L;
• TBIL\<40μmol/L;
• No YMDD mutation of the HBV drug resistance gene
• Subjects agree not to participate in any other clinical trial or take any other anti-HBV therapeutics during the study;
• Subjects understand and sign the ICF which approved by EC, and are able to comply with the study procedures and complete the study.

You may not qualify if:

• Was suspected with HCC by the following evidence:
• B-Ultrasound or imaging which shows occupying lesions;
• Continuingly elevating serum AFP level even if the B-Ultrasound is normal;
• AFP \>100ng/ml;
• With acute hepatic decompensation caused by liver disease aggravation or with clinical symptoms of decompensated liver disease at baseline;
• Serum Cr≥1.5mg/dl (≥130μmol/l) at the time of screening;
• Serum amylase \> two-fold of the upper limit of the normal reference value;
• Hb (male\<100g/ L, female\<90g/L), WBC\<3.5×10E9/L,PLT\<60×10E9/L (except hypersplenism and cirrhosis);
• Co-infection with HCV (anti-HCV positive), HIV and anti-HAV IgM positive, anti-HDV IgM positive, anti-HEV IgM positive, anti-CMV IgM positive and autoimmune hepatitis (e.g. antinuclear antibody titer\>1:160 ) or other active liver disease caused by known or unknown factors;
• Any other serious disease or active diseases other than hepatitis B that are considered by investigators to be potential factors that may interfere with the therapy, assessment or compliance with the protocol, including any uncontrolled diseases with clinical significance, e.g. kidney, heart, lung, blood vessel, neurogenic, digestive system and metabolic diseases (diabetes, hyperthyroidism, adrenal gland diseases), autoimmune dysfunctions, and tumors, etc;
• History of alcohol or drug abuse that is considered by investigators that could affect subject's compliance with the protocol or could influence the result of the analysis;
• Pregnant or breast-feeding female subjects, or those who plan to be pregnant during the course of the study or male subjects' companions who plan to be pregnant during the course of the study;
• Having used immunosuppressive agents, immunomodulators (thymosin), cytotoxic drugs within 6 months or transaminase-decreasing drugs within one month prior to the initiation of this study;
• Having used anti-HBV drugs (Lamivudine, interferon, adefovir, entecavir, or sebivo, etc.) within 6 months prior to the initiation of this study;
• Had or planning to have liver transplantation;

Sponsors & Collaborators

• Fuqiang Yang: lead

Study Sites (1)

Guiqiang Wang

Beijing, Bejing, 10000, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fuqiang Yang, PhD

CONTACT

00862087376240; yangfq23@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Immunology and Biochemistry, Guangzhou 458 Hospital

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: December 8, 2011
• Study Start: September 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 8, 2011

Record last verified: 2011-09

Locations

CN (1)