search
Back to results

A Randomized Study to Assess the Loss of HbsAg After a 48-week Treatment Period With Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B (PEGAN)

Primary Purpose

Chronic Hepatitis B, AgHbs Negativation

Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Pegylated interferon-alpha-2a
Nucleotidic or Nucleosidic Treatment
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Positive Hbs Ag
  • Negative HbeAg
  • Plasma HBV DNA undetectable at pre-inclusion ever since 12 months
  • ALT less than or equal to 5 times the upper limit of normal
  • Non cirrhotic or Not Decompensated Cirrhosis (Child Pugh <7)
  • Undetectable hepatocellular carcinoma in liver scan and / or alpha-fetoprotein rate <50 ng / ml
  • Unchanged nucleoside (s) and / or nucleotide (s) treatment for at least three months (and not including telbivudine)
  • Negative pregnancy test for childbearing women
  • Signed informed consent
  • Use of contraception for childbearing women

Exclusion Criteria:

  • Polymorphonuclear neutrophils <1500/mm3
  • Platelets <70.000/mm3
  • Co-infections with HIV, HCV and / or HDV
  • Prolonged excessive consumption of alcohol
  • Active intravenous drug addiction
  • Immunomodulators Treatment(eg interferons), ever since one year
  • Immunosuppressive treatments terminated ever since one year
  • Telbivudine treatment
  • Long course steroid treatment (more than 4 weeks) by oral way
  • History of severe epilepsy or current use of anticonvulsants
  • Severe heart disease (eg heart failure stage III or IV NYHA class, myocardial infarction less than 6 months, ventricular arrhythmia requiring treatment, unstable angina or other significant cardiovascular disease)
  • Chronic liver disease other than HBV-related (hemochromatosis, autoimmune hepatitis, metabolic liver disease, including Wilson's disease and a deficiency of alpha1-antitrypsin deficiency, alcoholic liver disease, exposure to toxins)
  • Presence or suspicion of cancer or a history of cancer (except basal cell carcinoma or in situ carcinoma) within 5 years preceding the randomization
  • Thyroid uncontrolled disease, abnormal TSH, elevated thyroid antibodies and clinical manifestations of thyroid dysfunction
  • History of autoimmune disease (inflammatory digestive, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis ....) Or presence of autoantibodies at a significant rate
  • Renal impairment (creatinine clearance <50 ml / min using the Cockroft formula), renal transplantation, hemodialysis
  • Hypersensitivity to the active substance, interferon alpha or any component
  • History of depression or psychiatric disorders and uncontrolled depression or uncontrolled psychiatric disorders
  • Pregnancy or breastfeeding, or wish of pregnancy during the study period.
  • Patients under legal protection or unable to express their consent

Sites / Locations

  • Hôpital Saint Joseph, Service d'hépatogastroentérologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PegIFN + Nucleosidic or Nucleotidic Analog

Nucleosidic or Nucleotidic Analog

Arm Description

Outcomes

Primary Outcome Measures

HbsAg negativation at week 96
Percentage of patients with negative HbsAg at W96, i.e 12 months after a 48 weeks treatment with pegylated interferon

Secondary Outcome Measures

Kinetics of HbsAg
Kinetics of HbsAg under treatment at W-6, W0, W12, W24 and W48 and after discontinuation of PegIFN alpha 2a at W72, W20 and W144

Full Information

First Posted
July 28, 2010
Last Updated
March 28, 2013
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Roche Pharma AG
search

1. Study Identification

Unique Protocol Identification Number
NCT01172392
Brief Title
A Randomized Study to Assess the Loss of HbsAg After a 48-week Treatment Period With Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B
Acronym
PEGAN
Official Title
A Randomized, Multicenter, Unblinded, Phase III Study Assessing the Loss of HbsAg at W96 After a 48-week Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B (HbeAg Negative) Under Treatment and Responders (Undetectable Viral Load) to a Nucleoside(s) or Nucleotide(s) Analog(s) Treatment for at Least 12 Months. ANRS HB 06 Pegan
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Unknown status
Study Start Date
January 2011 (undefined)
Primary Completion Date
June 2015 (Anticipated)
Study Completion Date
June 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Roche Pharma AG

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the loss of HbsAg after a 48-week pegylated interferon alpha 2a in patients with chronic hepatitis B (HBeAg negativation)
Detailed Description
The purpose of this study is to provide a therapeutical alternative to the use of an extended or undeterminated duration of treatment with prolonged nucleoside (s)/nucleotide (s)analog (s). The duration of administration is not consensual, and in most cases followed by a virological relapse, so that, the prolonged use could lead to the occurrence of viral resistance and mutations. It is therefore expected that treatment with pegylated interferon for 48 weeks in patients with undetectable HBV DNA by analog(s) may increase and promotes the loss of HbsAg and then promotes HbsAg seroconversion. In the absence of cirrhosis, the loss of HbsAg at 6 months would allow the end of treatment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B, AgHbs Negativation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
185 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PegIFN + Nucleosidic or Nucleotidic Analog
Arm Type
Experimental
Arm Title
Nucleosidic or Nucleotidic Analog
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon-alpha-2a
Intervention Description
180 mcg / wk / SC from D0 to W48
Intervention Type
Drug
Intervention Name(s)
Nucleotidic or Nucleosidic Treatment
Intervention Description
Analog treatment according to investigators practice
Primary Outcome Measure Information:
Title
HbsAg negativation at week 96
Description
Percentage of patients with negative HbsAg at W96, i.e 12 months after a 48 weeks treatment with pegylated interferon
Time Frame
W96
Secondary Outcome Measure Information:
Title
Kinetics of HbsAg
Description
Kinetics of HbsAg under treatment at W-6, W0, W12, W24 and W48 and after discontinuation of PegIFN alpha 2a at W72, W20 and W144
Time Frame
W-6, W0, W12, W24 and W48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Positive Hbs Ag Negative HbeAg Plasma HBV DNA undetectable at pre-inclusion ever since 12 months ALT less than or equal to 5 times the upper limit of normal Non cirrhotic or Not Decompensated Cirrhosis (Child Pugh <7) Undetectable hepatocellular carcinoma in liver scan and / or alpha-fetoprotein rate <50 ng / ml Unchanged nucleoside (s) and / or nucleotide (s) treatment for at least three months (and not including telbivudine) Negative pregnancy test for childbearing women Signed informed consent Use of contraception for childbearing women Exclusion Criteria: Polymorphonuclear neutrophils <1500/mm3 Platelets <70.000/mm3 Co-infections with HIV, HCV and / or HDV Prolonged excessive consumption of alcohol Active intravenous drug addiction Immunomodulators Treatment(eg interferons), ever since one year Immunosuppressive treatments terminated ever since one year Telbivudine treatment Long course steroid treatment (more than 4 weeks) by oral way History of severe epilepsy or current use of anticonvulsants Severe heart disease (eg heart failure stage III or IV NYHA class, myocardial infarction less than 6 months, ventricular arrhythmia requiring treatment, unstable angina or other significant cardiovascular disease) Chronic liver disease other than HBV-related (hemochromatosis, autoimmune hepatitis, metabolic liver disease, including Wilson's disease and a deficiency of alpha1-antitrypsin deficiency, alcoholic liver disease, exposure to toxins) Presence or suspicion of cancer or a history of cancer (except basal cell carcinoma or in situ carcinoma) within 5 years preceding the randomization Thyroid uncontrolled disease, abnormal TSH, elevated thyroid antibodies and clinical manifestations of thyroid dysfunction History of autoimmune disease (inflammatory digestive, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis ....) Or presence of autoantibodies at a significant rate Renal impairment (creatinine clearance <50 ml / min using the Cockroft formula), renal transplantation, hemodialysis Hypersensitivity to the active substance, interferon alpha or any component History of depression or psychiatric disorders and uncontrolled depression or uncontrolled psychiatric disorders Pregnancy or breastfeeding, or wish of pregnancy during the study period. Patients under legal protection or unable to express their consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc BOURLIERE, MD
Organizational Affiliation
Hôpital Saint Joseph, Service d'hépatogastroentérologie, Marseille
Official's Role
Study Chair
Facility Information:
Facility Name
Hôpital Saint Joseph, Service d'hépatogastroentérologie
City
Marseille
ZIP/Postal Code
13008
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
28404133
Citation
Bourliere M, Rabiega P, Ganne-Carrie N, Serfaty L, Marcellin P, Barthe Y, Thabut D, Guyader D, Hezode C, Picon M, Causse X, Leroy V, Bronowicki JP, Carrieri P, Riachi G, Rosa I, Attali P, Molina JM, Bacq Y, Tran A, Grange JD, Zoulim F, Fontaine H, Alric L, Bertucci I, Bouvier-Alias M, Carrat F; ANRS HB06 PEGAN Study Group. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial. Lancet Gastroenterol Hepatol. 2017 Mar;2(3):177-188. doi: 10.1016/S2468-1253(16)30189-3. Epub 2017 Jan 20.
Results Reference
derived
Links:
URL
http://www.anrs.fr
Description
French National Agency for Research on AIDS and viral hepatitis website

Learn more about this trial

A Randomized Study to Assess the Loss of HbsAg After a 48-week Treatment Period With Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B

We'll reach out to this number within 24 hrs