- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03332329
Sequential/Combination Therapy in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients (NPGV)
November 1, 2017 updated by: Qin Ning
Efficacy and Safety of Combination Therapy With Entecavir, Peginterferon Alfa-2b and Immunomodulators in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients
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).
Study Overview
Status
Unknown
Conditions
Detailed Description
Patents who were treated with NA at least one year and achieved HBV DNA suppression are enrolled in this study, they will receive Entecavir (ETV) for 60 weeks, HBV vaccine (60ug/month, every four weeks) for 24 weeks, GMCSF (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84, and Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 4
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 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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;
- 2000 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.
Exclusion Criteria:
- 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;
- Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
- Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
- Serum creatinine level > 1.5 ULN in screening period.
- Phosphorus < 0.65 mmol/L;
- antinuclear antibody (ANA) > 1:100;
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
- History of a severe seizure disorder or current anticonvulsant use;
- History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
- History of chronic pulmonary disease associated with functional limitation;
- Diseases that interferon and Nucleotides or nucleosides are not suitable.
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: Sequential combination arm
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
|
Entecavir is used for 96 weeks
Other Names:
Granulocyte-macrophage colony stimulating factor is used intermittently from baseline to week 16 and from 60 to week 84
Other Names:
Y peginterferon alfa-2b is used for 96 weeks
Other Names:
60ug HBV vaccine is used every four week for 24 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HBsAg loss rate
Time Frame: at week 108
|
Percentages of patients who achieve HBsAg loss at the end of treatment
|
at week 108
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HBsAg level
Time Frame: at week 60
|
Dynamic change in HBsAg level from baseline to the end of treatment
|
at week 60
|
HBsAg level
Time Frame: at week 108
|
Dynamic change in HBsAg level from baseline to the end of treatment
|
at week 108
|
decline in HBsAg level
Time Frame: at week 60
|
Decline in HBsAg level from baseline to the end of treatment
|
at week 60
|
decline in HBsAg level
Time Frame: at week 108
|
Decline in HBsAg level from baseline to the end of treatment
|
at week 108
|
HBsAb appearance rate
Time Frame: at week 108
|
Percentages of HBsAb appearance at the end of treatment
|
at week 108
|
HBsAb seroconversion rate
Time Frame: at week 108
|
Percentages of HBsAb seroconversion at the end of treatment
|
at week 108
|
HBeAg loss rate
Time Frame: at week 108
|
Percentages of HBeAg loss in the HBeAg-positive patients at the end of treatment
|
at week 108
|
HBeAg seroconversion rate
Time Frame: at week 108
|
Percentages of HBeAg seroconversion in the HBeAb-negative patients at the end of treatment
|
at week 108
|
Rate of HBV DNA level <1000 copies/mL
Time Frame: at week 108
|
Percentages of HBV DNA level <1000 copies/mL at the end of treatment
|
at week 108
|
Rate of alanine aminotransferase (ALT) normalisation
Time Frame: at week 108
|
Percentages of ALT normalisation at the end of treatment
|
at week 108
|
Sustained HBsAg loss rate
Time Frame: at week 156
|
Percentages of sustained HBsAg loss at the end of follow-up
|
at week 156
|
The rate of progression to cirrhosis
Time Frame: at week 156
|
The rate of progression to cirrhosis at the end of follow-up
|
at week 156
|
The incidence rate of hepatocarcinoma
Time Frame: at week 156
|
The incidence rate of hepatocarcinoma at the end of follow-up
|
at week 156
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Qin Ning, Tongji Hospital
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 (Actual)
December 1, 2015
Primary Completion (Anticipated)
December 31, 2018
Study Completion (Anticipated)
December 31, 2019
Study Registration Dates
First Submitted
October 29, 2017
First Submitted That Met QC Criteria
November 1, 2017
First Posted (Actual)
November 6, 2017
Study Record Updates
Last Update Posted (Actual)
November 6, 2017
Last Update Submitted That Met QC Criteria
November 1, 2017
Last Verified
November 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Vaccines
- Entecavir
- Peginterferon alfa-2b
- Sargramostim
- Molgramostim
Other Study ID Numbers
- NPGV study
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
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.
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