UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Study on usefulness of PEG-IFN alpha-2a administration to discontinue nucleos(t)ide analogue treatment in patients with chronic hepatitis B
Title of the study (Brief title)	Usefulness of PEG-IFN alpha-2a to discontinue NA treatment
Region	Japan

Condition
Condition	Chronic hepatitis B
Classification by specialty	Hepato-biliary-pancreatic medicine
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	To clarify usefulness of PEG-IFN alpha-2a administration to discontinue NA treatment in patients with chronic hepatitis B
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	HBe antigen status, amount of HBV DNA, and ALT level at 24 and 48 weeks after stopping PEG-IFN administration.
Key secondary outcomes	1. HBe antigen status, amount of HBV DNA, and ALT level at 24 weeks after stopping PEG-IFN administration. 2. Changes in amount of viral antigens including HBs antigen during and after PEG-IFN administration.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Self control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Start PEG-IFN alpha 2a administration just after stopping NA.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Patients with chronic hepatitis B who have been treated with NA for more than one years. 2. Patients who understand a risk of hepatitis relapse after stopping NA. 3. Patients who can be followed properly after stopping NA. 4. Patients whose informed consent was obtained.
Key exclusion criteria	1. Patients with impaired liver function. 2. Patients with advance liver fibrosis. 3. Patients with other serious diseases. 4. Women who are pregnant or those who have a possibility to be pregnant. 5. Patients who have a contra-indication for receiving PEG-IFN alpha-2a treatment.
Target sample size	100

Research contact person
Name of lead principal investigator	EIJI TANAKA
Organization	Shinshu University School of Medicine
Division name	Department of Medicine
Address	Asahi 3-1-1, Matsumoto, Nagano-ken
TEL	0263-37-2634
Email	etanaka@shinshu-u.ac.jp

Public contact
Name of contact person	EIJI TANAKA
Organization	Shinshu University School of Medicine
Division name	Department of Medicine
Address	Asahi 3-1-1, Matsumoto, Nagano-ken
TEL	0263-37-2634
Homepage URL
Email	etanaka@shinshu-u.ac.jp

Sponsor
Institute	Department of Medicine, Shinshu University School of Medicine
Institute
Department

Funding Source
Organization	Ministry of Health, Labour and Welfare
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Division of Hepatobiliary and Pancreatic Medicine, Hyogo College of Medicine
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	信州大学医学部附属病院（長野県）、兵庫医科大学病院（兵庫県）、千葉大学医学部附属病院（千葉県）、聖マリアンナ医科大学病院（神奈川県）、名古屋市立大学病院（愛知県）、長崎医療センター（長崎県）、大阪市立大学医学部附属病院（大阪府）、大阪医科大学附属病院（大阪府）、東海大学医学部附属病院（神奈川県）、岡山大学病院（岡山県）、 川崎医科大学附属病院（岡山県）、広島大学病院（広島県）、手稲渓仁会病院（北海道）、武蔵野赤十字病院（東京都）、山形大学医学部附属病院（山形県）、横浜市立大学附属病院（神奈川県）、くまもと森都総合病院（熊本県）、熊本大学医学部附属病院（熊本県）、福岡大学病院（福岡県）、虎の門病院（東京都）、山梨大学医学部附属病院（山梨県）、香川県立中央病院（香川県）、大阪大学医学部附属病院（大阪府）

Other administrative information
Date of disclosure of the study information	2012 Year 01 Month 10 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 01 Month 06 Day
Anticipated trial start date	2012 Year 02 Month 01 Day
Last follow-up date	2016 Year 11 Month 30 Day
Date of closure to data entry	2016 Year 11 Month 30 Day
Date trial data considered complete	2016 Year 11 Month 30 Day
Date analysis concluded	2017 Year 06 Month 04 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://www.ncbi.nlm.nih.gov/pubmed/28634723
Results	BACKGROUND: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. METHODS: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 microg/dose weekly for 48 weeks. RESULTS: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-lambda3, which might have contributed to the reduction in patient HBsAg levels. CONCLUSIONS: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.
Other related information

Management information
Registered date	2012 Year 01 Month 10 Day
Last modified on	2017 Year 07 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000008285