UMIN-CTR Clinical Trial

Public title

Efficacy and safety of Entecavir/PEG-IFN-alpha sequential therapy for chronic active hepatitis B

Acronym

Entecavir/PEG-IFN-alpha sequential therapy for chronic hepatitis B (B-SHOOT study)

Scientific Title

Efficacy and safety of Entecavir/PEG-IFN-alpha sequential therapy for chronic active hepatitis B

Scientific Title:Acronym

Entecavir/PEG-IFN-alpha sequential therapy for chronic hepatitis B (B-SHOOT study)

Region

Japan

Condition

chronic active hepatitis B

Classification by specialty

Medicine in general

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To assess the efficacy and safety of entecavir/PEG-IFN-alpha sequential therapy for patients with chronic active hepatitis B

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

negative HBeAg, undetectable HBV DNA, and normal ALT at 6 months after the end of treatment

Key secondary outcomes

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

PEG-IFN-alpha 180mcg given by subcutaneous injection once a week for 48 weeks. In the first 4 weeks, Entecavir 0.5mg also given orally once daily.

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

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients with chronic active hepatitis B who have been treated with Entecavir for 36-72 weeks

Key exclusion criteria

1. presence of resistance to nucleoside analog (such as lamivudine and entecavir)
2. decompensated liver disease (total bilirubin >=2.0 mg/dL, prothrombin time <70 %, and albumin <3.6 g/dL)
3. other likely causes of chronic liver disease, such as autoimmune or alcoholic liver disease
4. severe complication (ex. impaired renal, cardiac or respiratory function)
5. women who are possibly pregnant, expectant mothers, and lactating mothers
6. history of interstitial pneumonitis
7. drug allegy to interferon
8. depression or other severe psychosomatic disorders
9. Unacceptable values of complete blood counts as follows:
i) WBC counts=<3,000/microL
ii) Neutrophil counts=<1,500/microL
iii) Hemoglobin concentration=<12g/dL
iv) Platelet counts=<90,000/microL

Target sample size

50

Name of lead principal investigator

1st name	Masaru
Middle name
Last name	Enomoto

Organization

Osaka City University Graduate School of Medicine

Division name

Department of Hepatology

Zip code

545-8585

Address

1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

TEL

06-6645-3905

Email

enomoto-m@med.osaka-cu.ac.jp

Name of contact person

1st name	Masaru
Middle name
Last name	Enomoto

Organization

Osaka City University Graduate School of Medicine

Division name

Department of Hepatology

Zip code

545-8585

Address

1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

TEL

06-6645-3811

Homepage URL

Email

enomoto-m@med.osaka-cu.ac.jp

Institute

Department of Hepatology, Osaka City University Graduate School of Medicine

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethical Committee of Osaka City University Graduate School of Medicine

Address

1-2-7 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Tel

06-6645-3457

Email

ethics@med.osaka-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2015

Year

03

Month

31

Day

URL releasing protocol

https://onlinelibrary.wiley.com/doi/10.1111/hepr.13050

Publication of results

Unpublished

URL related to results and publications

https://onlinelibrary.wiley.com/doi/10.1111/hepr.13050

Number of participants that the trial has enrolled

24

Results

A sustained biochemical, virologic, and serologic response was seen in 7/24 patients at 48 weeks post-treatment (2/14 HBeAg+ vs 5/10 HBeAg-, P=.085). At baseline, patients with a sustained response had significantly lower GGT (P=.0023), APRI (P=.049), and AFP levels (P=.042) than those without. The decline in HBsAg levels during the first 24 weeks of PegIFN2a treatment was greater in patients with a sustained response (P=.017). Additionally, HBsAg seroclearance was achieved in two patients (8.3%).

Results date posted

2024

Year

07

Month

05

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

In this study, 24 patients with CHB (14 hepatitis B envelope antigen [HBeAg]-positive patients and 10 HBeAg-negative patients) received entecavir for 36-52 weeks, followed by entecavir plus Peg-IFN2a for 4 weeks, and finally by PegIFN2a alone for 44 weeks.

Participant flow

The inclusion criteria were as follows: (i) persistent or fluctuating elevations of serum ALT levels for at least 6 months before the start of therapy; (ii) presence of hepatitis B surface antigen (HBsAg) in serum; (iii) presence of HBV-DNA >104 copies/mL (equivalent to 2000 IU/mL); (iv) no use of corticosteroids or immunomodulatory drugs, including IFN, within 1 year before the start of therapy; (v) no use of NAs, such as lamivudine, within 1 year before the start of therapy; (vi) absence of resistance to NAs; (vii) absence of antibodies to hepatitis C virus and other likely causes of chronic liver disease; and (viii) no clinical signs of decompensated cirrhosis or hepatocellular carcinoma.

Adverse events

Commonly known Peg-IFN2a adverse events such as general fatigue and influenza symptoms were present in almost all patients.

Outcome measures

All patients were followed up for at least 48 weeks after completion of treatment, and responses to therapy were assessed as follows: a biochemical response was defined as a decrease in serum ALT levels to within the normal range; a virologic response was defined as a decrease in serum HBV-DNA to <104 copies/mL; and a serologic response was defined as loss of serum HBeAg. A sustained response was defined as fulfillment of the criteria for biochemical, virologic, and serologic responses at 48 weeks after the end of therapy.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2011

Year

12

Month

06

Day

Date of IRB

2011

Year

12

Month

06

Day

Anticipated trial start date

2012

Year

01

Month

01

Day

Last follow-up date

2023

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

12

Month

24

Day

Last modified on

2024

Year

07

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008122

Single case data URL

Value
https://center6.umin.ac.jp/ice/8122