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A Real-World Study of Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B (COST)

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ClinicalTrials.gov Identifier: NCT03357822
Recruitment Status : Recruiting
First Posted : November 30, 2017
Last Update Posted : April 25, 2018
Sponsor:
Information provided by (Responsible Party):
Qin Ning, Tongji Hospital

Study Description
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Brief Summary:
The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Pegylated interferon Drug: Entecavir Drug: Tenofovir disoproxil fumarate Phase 4

Detailed Description:
Patents who were treated with NA at least one year and achieved hepatitis B virus (HBV) DNA suppression and HBsAg level<3000 international unit (IU) /mL are enrolled in this study, they are assigned into two groups, in group I, patients will receive pegylated interferon plus entecavir/tenofovir for 48/72/96 weeks, in group II, patients will receive entecavir/tenofovir for 96 weeks. HBsAg loss rates at the end of treatment and sustained response at the end of follow up will be evaluated.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B
Actual Study Start Date : January 25, 2018
Estimated Primary Completion Date : January 25, 2022
Estimated Study Completion Date : July 25, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Sequential combination therapy group
Patients are treated with pegylated Interferon (180ug, subcutaneously, once a week) plus entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 48/72/96 weeks
 Drug: Pegylated interferon
180ug Pegylated interferon is injected subcutaneously once a week
Other Name: Pegylated interferon (PegIFN)

Drug: Entecavir
0.5mg entecavir is orally taken every day
Other Name: Entecavir (ETV)

Drug: Tenofovir disoproxil fumarate
300mg tenofovir is orally taken every day
Other Name: Tenofovir disoproxil fumarate (TDF)
Active Comparator: Nucleoside therapy group
Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks
 Drug: Entecavir
0.5mg entecavir is orally taken every day
Other Name: Entecavir (ETV)

Drug: Tenofovir disoproxil fumarate
300mg tenofovir is orally taken every day
Other Name: Tenofovir disoproxil fumarate (TDF)


Outcome Measures
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Primary Outcome Measures :
  1. HBsAg loss rate [ Time Frame: at week 48 ]
    Percentages of patients who achieve HBsAg loss at week 48


Secondary Outcome Measures :
  1. HBsAg loss rate [ Time Frame: at week 72 ]
    Percentages of patients who achieve HBsAg loss at week 72

  2. HBsAg loss rate [ Time Frame: at week 96 ]
    Percentages of patients who achieve HBsAg loss at week 96

  3. HBsAg level [ Time Frame: at week 48 ]
    Dynamic change in HBsAg level from baseline to week 48

  4. HBsAg level [ Time Frame: at week 72 ]
    Dynamic change in HBsAg level from baseline to week 72

  5. HBsAg level [ Time Frame: at week 96 ]
    Dynamic change in HBsAg level from baseline to week 96

  6. sustained HBsAg loss rate [ Time Frame: at week 120 ]
    Percentages of patients who achieve HBsAg loss at week 120

  7. decline in HBsAg level [ Time Frame: at week 48 ]
    Decline in HBsAg level from baseline to week 48

  8. decline in HBsAg level [ Time Frame: at week 72 ]
    Decline in HBsAg level from baseline to week 72

  9. decline in HBsAg level [ Time Frame: at week 96 ]
    Decline in HBsAg level from baseline to week 96

  10. HBsAb appearance rate [ Time Frame: at week 48 ]
    Percentages of HBsAb appearance at week 48

  11. HBsAb appearance rate [ Time Frame: at week 72 ]
    Percentages of HBsAb appearance at week 72

  12. HBsAb appearance rate [ Time Frame: at week 96 ]
    Percentages of HBsAb appearance at week 96

  13. HBsAb seroconversion rate [ Time Frame: at week 48 ]
    Percentages of HBsAb seroconversion at week 48

  14. HBsAb seroconversion rate [ Time Frame: at week 72 ]
    Percentages of HBsAb seroconversion at week 72

  15. HBsAb seroconversion rate [ Time Frame: at week 96 ]
    Percentages of HBsAb seroconversion at week 96

  16. HBeAg loss rate [ Time Frame: at week 48 ]
    Percentages of HBeAg loss in the HBeAg-positive patients at week 48

  17. HBeAg loss rate [ Time Frame: at week 72 ]
    Percentages of HBeAg loss in the HBeAg-positive patients at week 72

  18. HBeAg loss rate [ Time Frame: at week 96 ]
    Percentages of HBeAg loss in the HBeAg-positive patients at week 96

  19. HBeAg seroconversion rate [ Time Frame: at week 48 ]
    Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 48

  20. HBeAg seroconversion rate [ Time Frame: at week 72 ]
    Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 72

  21. HBeAg seroconversion rate [ Time Frame: at week 96 ]
    Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 96

  22. Rate of HBV DNA level <1000 copies/mL [ Time Frame: at week 96 ]
    Percentages of HBV DNA level <1000 copies/mL at week 96

  23. Rate of alanine aminotransferase (ALT) normalization [ Time Frame: at week 96 ]
    Percentages of ALT normalization at week 96

  24. The rate of progression to cirrhosis [ Time Frame: at week 120 ]
    The rate of progression to cirrhosis at week 120

  25. The incidence rate of hepatocarcinoma [ Time Frame: at week 120 ]
    The incidence rate of hepatocarcinoma at week 120


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients from 18 to 65 years of age;
  2. HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
  3. Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;
  4. Serum HBV DNA ≤ 500 copies/ml;
  5. HBsAg<3000 IU/ml;
  6. HBsAg positive;
  7. 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;
  8. Absence of cirrhosis confirmed by ultrasonic test;
  9. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

  1. HBV DNA > 500 copies/ml;
  2. 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;
  3. Women with ongoing pregnancy or breast-feeding;
  4. 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);
  5. ALT >10 ULN;
  6. 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:
  7. one of the following 5 conditions are met, the patient has to be excluded:
  8. Serum albumin < 3.5 g/L;
  9. Prothrombin time > 3 seconds prolonged;
  10. Serum bilirubin > 34 µ mol/L;
  11. History of encephalopathy;
  12. History of variceal bleeding;
  13. Ascites;
  14. 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);
  15. 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;
  16. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
  17. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
  18. Serum creatinine level > 1.5 ULN in screening period.
  19. Phosphorus < 0.65 mmol/L;
  20. antinuclear antibody (ANA) > 1:100;
  21. 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;
  22. History of a severe seizure disorder or current anticonvulsant use;
  23. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
  24. History of chronic pulmonary disease associated with functional limitation;
  25. Diseases that interferon and nucleotides or nucleosides are not suitable.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03357822


Contacts
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Contact: Qin Ning 86 27 83662391 qning@vip.sina.com
Contact: Di Wu 86 27 83662391 woody_1984@163.com

Locations
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China, Beijing
302 Military Hospital of China Recruiting
Beijing, Beijing, China
Contact: Junliang Fu         
BeiJing YouAn Hospital, Capital Medical University Not yet recruiting
Beijing, Beijing, China
Contact: Xinyue Chen, Doctor         
China, Chongqing
The First Hospital Affiliated to AMU Not yet recruiting
Chongqing, Chongqing, China
Contact: Xuqing Zhang         
China, Fujian
The First Affiliated Hospital of Fujian Medical University Not yet recruiting
Fuzhou, Fujian, China
Contact: Jiaji Jiang, Doctor         
China, Guangxi
The First Affiliated Hospital of Guangxi Medical University Not yet recruiting
Nanning, Guangxi, China
China, Hangzhou
The First Affiliated Hospital of College of Medicine, Zhejiang University Not yet recruiting
Zhejiang, Hangzhou, China, Doctor
Contact: Qi Xia         
China, Hunan
Departmen of infectious disease, Xiangya Hospital, Central-south Universit Not yet recruiting
Changsha, Hunan, China
Contact: Deming Tan, Doctor         
The Second Xiangya Hospital of Central South University Not yet recruiting
Changsha, Hunan, China
Contact: Guozhong Gong         
China, Jiangsu
The First Affiliated Hospital with Nanjing Medical University Not yet recruiting
Nanjing, Jiangsu, China
Contact: Chuanlong Zhu         
The Second Hospital of Nanjing Not yet recruiting
Nanjing, Jiangsu, China
Contact: Wei Zhao         
China, Xiamen
Traditional Chinese Medicine,Xiamen Hospital Not yet recruiting
Shantou, Xiamen, China
Contact: Qianguo Mao         
China, Zhejiang
The first affiliated hospital of Wenzhou medical universtiy Not yet recruiting
Wenzhou, Zhejiang, China
Contact: Yongping Chen, Doctor         
Sponsors and Collaborators
Tongji Hospital
Investigators
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Principal Investigator: Qin Ning Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
More Information
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Responsible Party: Qin Ning, Prof, Tongji Hospital
ClinicalTrials.gov Identifier: NCT03357822    
Other Study ID Numbers: COST study
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Qin Ning, Tongji Hospital:
Chronic hepatitis B
Nucleoside analog
Pegylated Interferon
Sequential combination therapy
HBsAg loss
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
 Hepadnaviridae Infections
DNA Virus Infections
Interferons
Tenofovir
Entecavir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents