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Trial record 70 of 440 for:    hepatitis b | Open Studies

Efficacy of Switching or Adding Pegylated Interferon in Chronic Hepatitis B Patients on Long Term Oral Antiviral Therapy (SWAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National University Health System, Singapore
Sponsor:
Collaborators:
Tan Tock Seng Hospital
Singapore Clinical Research Institute
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Seng Gee Lim, National University Health System, Singapore
ClinicalTrials.gov Identifier:
NCT01928511
First received: August 21, 2013
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

Patients with Chronic Hepatitis B on long term oral antiviral therapy have to continue treatment indefinitely unless they achieve HBeAg seroconversion or HBsAg seroclearance, when therapy can be stopped. While HBeAg seroconversion is a more achievable endpoint, only 20-25% of patients develop this after one year of oral antiviral therapy. HBsAg seroclearance is universally infrequent. Strategies to improve these endpoints such as combination oral antiviral therapy have not been generally successful and recently studies have examined the possibility of switching or adding peginterferon therapy. However these have not been tested adequately in the group of patients that have been on long term oral antiviral therapy. Consequently this study was conceived to evaluate whether switching or adding peginterferon compared to continuing oral antiviral therapy are more efficacious strategies. HBeAg positive and HBeAg negative patients (n=310)will be randomised to continue oral antiviral therapy, switch or add pegylated interferon for 48 weeks in a ratio of 1:2:2 respectively. The study endpoints are HBsAg seroclearance, reduction of qHBsAg >1 log, qHBsAg<200 IU/ml, HBeAg loss and seroconversion, and HBV DNA suppression, all at week 72.


Condition Intervention Phase
Chronic Hepatitis B
Drug: peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly
Drug: Nucleos(t)ide analogue therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SWITCH OR ADD PEGYLATED-INTERFERON IN CHRONIC HEPATITIS B PATIENTS ON LONG TERM NUCLEOS(T)IDE THERAPY (SWAP TRIAL)

Resource links provided by NLM:


Further study details as provided by National University Health System, Singapore:

Primary Outcome Measures:
  • Reduction in quantitative HBsAg>1 log [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • HBeAg loss [ Time Frame: week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HBsAg seroclearance [ Time Frame: week 72 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: week 72 ] [ Designated as safety issue: No ]
    In HBeAg positive patients at baseline

  • HBsAg <200 IU/ml [ Time Frame: week 72 ] [ Designated as safety issue: No ]
  • undetectable HBV DNA [ Time Frame: week 72 ] [ Designated as safety issue: No ]

Estimated Enrollment: 310
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Continued oral nucleos(t)ide therapy
Patients assigned to this arm will continue their nucleos(t) analogue
Drug: Nucleos(t)ide analogue therapy
Other Name: includes lamivudine, adefovir, entecavir, tenofovir or combinations thereof
Experimental: Add on peg-interferon
Patients assigned to this arm will continue their existing nucleos(t)ide therapy and also be assigned peg-interferon alpha 2b 1.5mcg/kg sc weekly
Drug: peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly Drug: Nucleos(t)ide analogue therapy
Other Name: includes lamivudine, adefovir, entecavir, tenofovir or combinations thereof
Experimental: switch to peg-interferon
Patients assigned to this arm will stop their existing nucleos(t)ide therapy after one month overlap after starting peg-interferon alpha 2b 1.5mcg/kg sc weekly
Drug: peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between 21 and 65 years old.
  • Documented to be HBsAg positive for ≥ 6 months.
  • On any nucleos(t)ide analogue (lamivudine, adefovir, entecavir or tenofovir)for ≥ 1 year
  • HBV DNA undetectable by RT PCR at screening
  • Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
  • Patient is able to give written consent prior to study start and to comply with the study requirements.
  • Women of childbearing age must have a negative serum (ß-HCG) pregnancy test taken with 14 days of starting therapy

Exclusion Criteria:

  • Evidence of decompensated liver disease or hepatocellular carcinoma.
  • Have any of the following laboratory tests within 4 weeks of study entry:
  • HIV antibody or HCV antibody or HDV antibody positivity
  • Absolute neutrophil count < 1.5 X 109/l or platelets < 90 x 109/l or hemoglobin < 13 g/dL for men or 12g/dL for women
  • serum albumin <35 g/l or serum bilirubin > 30 mg/l
  • creatinine > 1.5 times upper limit of normal
  • prothrombin time > 1.5 times control, uncorrected by Vitamin K therapy.
  • Any interferon, Immunomodulators, systemic cytotoxic agents, or systemic corticosteroids within 6 months before trial entry.
  • Prolonged exposure to known hepatotoxins such as alcohol or drugs.
  • History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, hematological disease or medical illness that in the investigator's opinion might interfere with therapy.
  • Malignant disease within 5 years of trial entry.
  • Women who are pregnant and who are not practicing adequate birth control measures, or who are lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01928511

Locations
Singapore
National University Hospital, Tan Tock Seng Hospital Recruiting
Singapore, Singapore
Contact: Seng Gee Lim, MBBS, FRACP, FRCP, MD    65-67724369    mdclimsg@nus.edu.sg   
Principal Investigator: Seng Gee Lim, MBBS, FRACP, FRCP, MD         
Principal Investigator: Wei Lyn Yang, MBBS, MRCP         
Sponsors and Collaborators
Seng Gee Lim
Tan Tock Seng Hospital
Singapore Clinical Research Institute
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Seng Gee Lim, Director of Hepatology, Dept of Gastroenterology and Hepatology, National University Health System, Singapore
ClinicalTrials.gov Identifier: NCT01928511     History of Changes
Other Study ID Numbers: MK4031-398, CIRG12may075
Study First Received: August 21, 2013
Last Updated: January 8, 2014
Health Authority: Singapore: Health Sciences Authority

Keywords provided by National University Health System, Singapore:
Hepatitis B virus
HBeAg positive
HBeAg negative
antiviral therapy
nucleoside analogues

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Hepatitis, Viral, Human
Peginterferon alfa-2b
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Interferons
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014