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

NCT01928511 | Completed Phase 4

• 2 other identifiers: MK4031-398CIRG12may075
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Chronic Hepatitis B

Keywords

Hepatitis B virus; HBeAg positive; HBeAg negative; antiviral therapy; nucleoside analogues

Outcome Measures

Primary Outcomes (2)

• Reduction in quantitative HBsAg>1 log

  Week 72

• HBeAg loss

  week 72

Secondary Outcomes (4)

• HBsAg seroclearance

  week 72

• HBeAg seroconversion

  week 72

• HBsAg <200 IU/ml

  week 72

• undetectable HBV DNA

  week 72

Study Arms (3)

Continued oral nucleos(t)ide therapy

ACTIVE COMPARATOR

Patients assigned to this arm will continue their nucleos(t) analogue

Drug: Nucleos(t)ide analogue therapy

Add on peg-interferon

EXPERIMENTAL

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

switch to peg-interferon

EXPERIMENTAL

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

Interventions

peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly DRUG

Add on peg-interferon; switch to peg-interferon

Nucleos(t)ide analogue therapy DRUG

Also known as: includes lamivudine, adefovir, entecavir, tenofovir or combinations thereof

Add on peg-interferon; Continued oral nucleos(t)ide therapy

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 21 and 70 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seng Gee Lim: lead
• Tan Tock Seng Hospital: collaborator
• Singapore Clinical Research Institute: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Singapore General Hospital: collaborator
• Changi General Hospital: collaborator

Study Sites (4)

Changi General Hospital

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Tan Tock Seng Hospital

Singapore, Singapore

Location

Related Publications (2)

• Huang DQ, Shen L, Phyo WW, Cloherty G, Butler EK, Kuhns MC, McNamara AL, Holzmayer V, Gersch J, Anderson M, Yang WL, Ngu JH, Chang J, Tan J, Ahmed T, Dan YY, Lee YM, Lee GH, Tan PS, Muthiah M, Khine HTW, Lee C, Tay A, Lim SG. Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon. Antiviral Res. 2024 Jul;227:105876. doi: 10.1016/j.antiviral.2024.105876. Epub 2024 Apr 17.

  PMID: 38641023 DERIVED

• Lim SG, Yang WL, Ngu JH, Chang J, Tan J, Ahmed T, Dan YY, Lim K, Lee YM, Lee GH, Tan PS, Wai KL, Phyo WW, Khine HHTW, Lee C, Tay A, Chan E. Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT. Clin Gastroenterol Hepatol. 2022 Feb;20(2):e228-e250. doi: 10.1016/j.cgh.2021.04.031. Epub 2021 Apr 22.

  PMID: 33895361 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

adefovir; entecavir; Tenofovir

Condition Hierarchy (Ancestors)

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)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Seng Gee Lim, MBBS, FRACP, FRCP, MD

  National University Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Hepatology, Dept of Gastroenterology and Hepatology

Model Details: Three arm parallel study randomised 1:2:2

Study Record Dates

• First Submitted: August 21, 2013
• First Posted: August 26, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 24, 2019

Record last verified: 2019-09

Locations

SG (4)