Sequential/Combination Therapy in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients

NCT03332329 | Unknown Phase 4 DMC

• 1 other identifier: NPGV study
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of the prospective study is to determine whether combination/ sequential therapy with Entecavir, Peginterferon alfa-2b and immunomodulators Granulocyte Macrophage Colony Stimulating Factor (GMCSF)+vaccine could induce HBsAg loss in chronic hepatitis B patients with maintained Hepatitis B Virus (HBV) DNA suppression on long-term nucleoside or nucleotide analogue (NA).

Conditions

Chronic Hepatitis b

Keywords

HBsAg; PegIFN; ETV; Chronic Hepatitis B (CHB); HBV; GMCSF

Outcome Measures

Primary Outcomes (1)

• HBsAg loss rate

  Percentages of patients who achieve HBsAg loss at the end of treatment

  at week 108

Secondary Outcomes (13)

• HBsAg level

  at week 60

• HBsAg level

  at week 108

• decline in HBsAg level

  at week 60

• decline in HBsAg level

  at week 108

• HBsAb appearance rate

  at week 108

Study Arms (1)

Sequential combination arm

EXPERIMENTAL

Drug: Entecavir for 60 weeks Drug: HBV vaccine (60ug/month, every four weeks) for 24 weeks Drug: Granulocyte Macrophage Colony Stimulating Factor (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84 Drug: Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108

Drug: Entecavir; Drug: Granulocyte Macrophage Colony Stimulating Factor; Drug: Y peginterferon alfa-2b; Drug: HBV vaccine

Interventions

Entecavir DRUG

Entecavir is used for 96 weeks

Also known as: ETV

Sequential combination arm

Granulocyte Macrophage Colony Stimulating Factor DRUG

Granulocyte-macrophage colony stimulating factor is used intermittently from baseline to week 16 and from 60 to week 84

Also known as: GMCSF

Sequential combination arm

Y peginterferon alfa-2b DRUG

Y peginterferon alfa-2b is used for 96 weeks

Also known as: peginterferon a-2b

Sequential combination arm

HBV vaccine DRUG

60ug HBV vaccine is used every four week for 24 weeks

Also known as: vaccine

Sequential combination arm

Eligibility Criteria

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

You may qualify if:

• Male and female patients from 18 to 65 years of age;
• HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
• Before nucleotides or nucleosides treatment, ALT \> 2 upper limit of normal value (ULN), HBV DNA \>10000 copies/ml, HBsAg positive;
• Serum HBV DNA \< 1000 copies/ml;
• IU/ml ≤HBsAg≤6000 IU/ml;
• HBsAg positive;
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;
• Absence of cirrhosis confirmed by ultrasonic test;
• Agree to participate in the study and sign the patient informed consent.

You may not qualify if:

• Patients who had NAs resistance and HBV DNA \> 1000 copies/ml, or treatment of drugs with interferon longer than 6 months;
• Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
• Women with ongoing pregnancy or breast-feeding;
• Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
• ALT \>10 ULN;
• Evidence of decompensated liver disease (Child-Pugh score \> 5). Child-Pugh \> 5 means, if one of the following 5 conditions are met, the patient has to be excluded:
• one of the following 5 conditions are met, the patient has to be excluded:
• Serum albumin \< 3.5 g/L;
• Prothrombin time \> 3 seconds prolonged;
• Serum bilirubin \> 34 µ mol/L;
• History of encephalopathy;
• History of variceal bleeding;
• Ascites;
• History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
• Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein \> 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values \< 20 ng/mL but \> 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;

Sponsors & Collaborators

• Qin Ning: lead

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Granulocyte-Macrophage Colony-Stimulating Factor; Vaccines

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Products; Complex Mixtures

Study Officials

• Qin Ning

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: October 29, 2017
• First Posted: November 6, 2017
• Study Start: December 1, 2015
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2019
• Last Updated: November 6, 2017

Record last verified: 2017-11