- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02560649
An Exploratory Study of RGT Strategy on Optimal NUC-experienced Patients
A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of "Response-Guided-Therapy (RGT)" Strategy on Optimal Nucleoside Analogue (NUC)-Experienced Patients
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female patients with age ≥18 and ≤65 years;
- There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative before treated with nucleoside analogue(NUC) (except of telbivudine);
- Treated with NUC (except of telbivudine)for more than 24 weeks and achieve HBV DNA<1000copies/ml and HBsAg<5000IU/ml;&HBeAg<100PEIU/ml(470s/co);
- Without contra-indications to Peginterferon alfa-2a therapy as detailed in the label;
- Without co-infection with hepatitis C, hepatitis D and HIV;
- Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
- Agree to participate in the study and sign the patient informed consent form.
Exclusion criteria
- Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV)
- AFP(alpha fetoprotein)>50ng/ml and/or evidence of hepatocellular carcinoma
Evidence of decompensated liver disease (Child-Pugh scores >5). Child-Pugh >5 means that, if one of the following 6 conditions is met, the patient has to be excluded:
- Serum albumin <35 g/L
- Prothrombin time prolonged≥ 4 seconds or PTA(prothrombin activity) < 60%
- Serum bilirubin > 34 µmol/L
- History of encephalopathy
- 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)
- Pregnant or breast-feeding Women
- ANC(absolute neutrophil count)<1.5x 10^9/L or PLT(platelet count)<90x 10^9/L
- Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months 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 immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
- History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease
- History of chronic pulmonary disease associated with functional limitation
- History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
- Hemodialysis patients or patients with renal insufficiency
- History of a severe seizure disorder or current anticonvulsant use
- Major organ transplantation or other evidence of severe illness, malignancy, or any other conditions, which would make the patient, in the opinion of the investigator, unsuitable for the study
- History of thyroid disease poorly controlled on prescribed medications
- Evidence of severe retinopathy or clinically relevant ophthalmologic disorder
- History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study
- Immunomodulatory treatment (including interferon) or LDT(telbivudine) within 1 year prior to the first dose of treatment
- Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A:PEG+NUC (HBsAg<200IU/ml at week 24)
Peginterferon alfa-2a 180μg /wk plus nucleoside analogue(NUC): HBsAg<200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks) |
Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
Other Names:
|
Active Comparator: B:PEG+NUC(HBsAg>200IU/ml at week 24)
Peginterferon alfa-2a 180μg /wk plus+nucleoside analogue(NUC): HBsAg>200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks) |
Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
Other Names:
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
Other Names:
|
Active Comparator: C:NUC(HBsAg>200IU/ml at week 24)
nucleoside analogue(NUC): HBsAg>200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks) |
Entecavir 0.5mg qd for 24 weeks(Arm C)
Other Names:
Lamivudine 0.1g qd for 24 weeks(Arm C)
Other Names:
Adefovir 10mg qd for 24 weeks(ArmC)
Other Names:
Tenofovir 300mg qd for 24 weeks(Arm C)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants who achieve HBsAg clearance
Time Frame: Week 48
|
To investigate whether HBsAg clearance rate can be improved at week 48 following applying RGT strategy(week 24) in NUC-experience subjects will be measured by the number of participants who achieve HBsAg clearance
|
Week 48
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants who achieve HBsAg seroconversion
Time Frame: Week 48
|
To investigate the HBsAg seroconversion rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBsAg seroconversion
|
Week 48
|
Number of participants who achieve HBeAg loss
Time Frame: Week 48
|
To investigate the HBeAg loss rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg loss
|
Week 48
|
Number of participants who achieve HBeAg seroconversion
Time Frame: Week 48
|
To investigate the HBeAg seroconversion rate at week 48 will be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg seroconversion
|
Week 48
|
Percentage of of participants who achieve HBsAg decline >2log from baseline(0 week)
Time Frame: Week 48
|
To investigate HBsAg decline from baseline at week 48 following applying RGT strategy in NUC-experience subjects by measured the percentage of of participants who achieve HBsAg decline>2log from baseline(0 week)
|
Week 48
|
Percentage of of participants who achieve HBsAg <10IU/mL
Time Frame: Week 48
|
To investigate the percentage of of participants who achieve HBsAg <100IU/mLat week 48 following applying RGT strategy in NUC-experience subjects
|
Week 48
|
Percentage of of participants who achieve combined response(defined as HBeAg seroconversion and HBVDNA<300copies/mL)
Time Frame: Week 48
|
To investigate the percentage of of participants who achieve combined response at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve combined response
|
Week 48
|
Percentage of of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<100IU/mL)
Time Frame: Week 48
|
To investigate the percentage of of participants who achieve dural response I at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
|
Week 48
|
Percentage of of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<10IU/mL)
Time Frame: Week 48
|
To investigate the percentage of of participants who achieve dural response II at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
|
Week 48
|
Number of participants who relapses (HBVDNA>1000copies/ml)
Time Frame: Week 48
|
To investigate the number of participants who relapses following applying RGT strategy in NUC-experience subjects
|
Week 48
|
Number of Participants with AE
Time Frame: Week 48
|
Number of participants with adverse events as a measure of safety and tolerability
|
Week 48
|
Number of Participants with SAE
Time Frame: Week 48
|
Number of participants with SAEs as a measure of safety and tolerability
|
Week 48
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.
- P. Hu et al. 2015 EASL abstract O116. PREDICTIVE VALUE OF BASELINE AND ON-TREATMENT qHBsAg LEVEL IN HBeAg POSITIVE CHB PATIENTS WHO SWITCHED FROM NUCS TO PEGYLATED INTERFERON A-2A: A FURTHER ANALYSIS FROM NEW SWITCH STUDY
- Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Hepatitis, Chronic
- Hepatitis
- Hepatitis B
- Hepatitis B, Chronic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Immunologic Factors
- Tenofovir
- Interferon-alpha
- Peginterferon alfa-2a
- Entecavir
- Lamivudine
- Adefovir
- Adefovir dipivoxil
Other Study ID Numbers
- PYRAMID
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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