Hepatitis B, ChronicPhase 3NCT00536263

PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)

A Phase 3 study testing pegylated interferon alpha-2b in people with Hepatitis B, Chronic, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: pegylated interferon alpha-2b
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 671 participants
Where: No sites listed yet
Study dates: Sep 2007to Nov 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults with chronic hepatitis B:
Serum hepatitis B surface antigen positive for at least 6 months
Serum hepatitis B e antigen positive
Serum negative for hepatitis B surface and e antibodies
Plasma hepatitis B virus deoxyribonucleic acid (DNA) level greater than 20,000 IU/mL
Alanine aminotransferase (ALT) 2- to 10-times the upper limit of normal
Compensated liver disease with certain minimum hematological and serum biochemical criteria

Who cannot join

Significant hepatic disease from an etiology other than hepatitis B virus
Antiviral treatment for hepatitis within previous 6 months
History of severe psychiatric disease, especially depression
Unstable or significant cardiovascular disease
Prolonged exposure to known hepatotoxins such as alcohol or drugs
Any condition that could interfere with the subject participating in and completing the study

About this study

Official title: An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients

The purpose of this study is to determine the efficacy and safety of two dosages of PegIntron for treating hepatitis B e antigen (HBeAg) positive chronic hepatitis B compared with the approved dosage, which is PegIntron 1.0 microgram (mcg)/kg given once a week for 24 weeks. This study compares dosages of (1) 1.5 mcg/kg once a week for 24 weeks and (2) 1.5 mcg/kg once a week for 48 weeks with the approved dosage. All subjects are followed for 24 weeks after their treatment ends.

Conditions: Hepatitis B, Chronic
Being tested: pegylated interferon alpha-2b
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pegylated interferon alpha-2bDrug
1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks
pegylated interferon alpha-2bDrug
1.5 mcg/kg S.C. QW for 24 weeks
pegylated interferon alpha-2bDrug
1.5 mcg/kg S.C. QW for 48 weeks

Study groups in NCT00536263
Study group	Role	What they receive
PEG 1.0 mcg/kg weekly (QW) * 24 weeks	Active comparator	PegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up Receives: Drug: pegylated interferon alpha-2b
PEG 1.5 mcg/kg QW * 24 wks	Experimental	PegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up Receives: Drug: pegylated interferon alpha-2b
PEG 1.5 mcg/kg QW * 48 wks	Experimental	PegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up Receives: Drug: pegylated interferon alpha-2b

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss
HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)
Measured: 24 weeks after end of treatment (EOT)

Secondary outcomes (10)

Number of Participants With HBeAg Loss
HBeAg Loss was tested by assay of Abbott MEIA
Measured: Up to Treatment Week 48
HBe Seroconversion
HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.
Measured: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL
HBV-DNA was tested by assay of Roche Cobas Taqman (the test
lowest limit is 6 IU/mL)
Measured: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With HBV-DNA < 200 IU/mL
HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL)
Measured: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With HBV-DNA Undetectable
Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR).
Measured: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Biochemical Response
Biochemical response was defined as alanine aminotransferase (ALT) normalization.
Measured: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Combined Response
Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization
Measured: End of treatment (EOT) and 24 weeks after EOT
Hepatitis B Surface Antigen (HBsAg) Loss
HBsAg Loss was tested by assay of Abbott MEIA
Measured: End of treatment (EOT) and 24 weeks after EOT
Hepatitis B Surface Antigen (HBs) Seroconversion
HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive
Measured: End of treatment (EOT) and 24 weeks after EOT
Change From Baseline in Liver Biopsy Score
Method for biopsy scoring was Knodell Scoring System (Histology Activity Index-HAI Score System):
Score I (periportal +/- bridging necrosis): 0 (none) to 10 (multilobular necrosis).
Score II (Intralobular degeneration and focal necrosis): 0 (none) to 4 (Marked [involvement of >2/3 of lobules or nodules]).
Score III (portal inflammation): 0 (none) to 4 (Marked [dense packing of
inflammatory cells in >2/3 of portal tracts]).
Score IV (fibrosis): 0 (none) to 4 (cirrhosis).
Measured: Baseline to 24 weeks after end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2007Nov 2009

First posted27 Sep 2007 (estimated)
Study startSep 2007
Primary completionNov 2009
Study completionNov 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 671 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00536263
Sponsor's protocol ID: P05170
Status last verified: Mar 2017
First submitted: 26 Sep 2007
Last updated: 7 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, Ren H, Ding H, Sheng J, Wei L, Chen S, Fan X, Huang W, Pan C, Gao Z, Zhang J, Zhou B, Chen G, Wan M, Tang H, Wang G, Yang Y, Mohamed R, Guan R, Lee TH, Chang WH, Zhenfei H, Ye Z, Xu D. Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial. J Clin Virol. 2014 Dec;61(4):509-16. doi: 10.1016/j.jcv.2014.08.008. Epub 2014 Aug 18.
PubMed 25200354

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Hepatitis B, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients
ClinicalTrials.gov ID: NCT00536263
Acronym / sponsor ID: P05170
Conditions: Hepatitis B, Chronic
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 671 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Sep 2007
Primary completion: Nov 2009 (actual)
Study completion: Nov 2009 (actual)
First posted: 27 Sep 2007 (estimated)
Results: Posted 21 Dec 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
PEG 1.0 mcg/kg weekly (QW) * 24 weeks	Active comparator	Drug: pegylated interferon alpha-2bPegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up
PEG 1.5 mcg/kg QW * 24 wks	Experimental	Drug: pegylated interferon alpha-2bPegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up
PEG 1.5 mcg/kg QW * 48 wks	Experimental	Drug: pegylated interferon alpha-2bPegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Adults with chronic hepatitis B:
Compensated liver disease with certain minimum hematological and serum biochemical criteria

Key exclusion criteria (6 listed)

Significant hepatic disease from an etiology other than hepatitis B virus
Antiviral treatment for hepatitis within previous 6 months
History of severe psychiatric disease, especially depression
Unstable or significant cardiovascular disease
Prolonged exposure to known hepatotoxins such as alcohol or drugs

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pegylated interferon alpha-2b1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks	Drug	PEG 1.0 mcg/kg weekly (QW) * 24 weeks
pegylated interferon alpha-2b1.5 mcg/kg S.C. QW for 24 weeks	Drug	PEG 1.5 mcg/kg QW * 24 wks
pegylated interferon alpha-2b1.5 mcg/kg S.C. QW for 48 weeks	Drug	PEG 1.5 mcg/kg QW * 48 wks

Primary outcome

Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss
Time frame: 24 weeks after end of treatment (EOT)
HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)

10 secondary outcomes

Number of Participants With HBeAg Loss
Time frame: Up to Treatment Week 48
HBe Seroconversion
Time frame: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL
Time frame: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With HBV-DNA < 200 IU/mL
Time frame: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With HBV-DNA Undetectable
Time frame: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Biochemical Response
Time frame: End of treatment (EOT) and 24 weeks after EOT
Number of Participants With Combined Response
Time frame: End of treatment (EOT) and 24 weeks after EOT
Hepatitis B Surface Antigen (HBsAg) Loss
Time frame: End of treatment (EOT) and 24 weeks after EOT
Hepatitis B Surface Antigen (HBs) Seroconversion
Time frame: End of treatment (EOT) and 24 weeks after EOT
Change From Baseline in Liver Biopsy Score
Time frame: Baseline to 24 weeks after end of treatment

Results and safety

Results posted to the registry on 21 Dec 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks	225	214
PEG 1.5 mcg/kg QW * 24 Weeks	221	207
PEG 1.5 mcg/kg QW * 48 Weeks	225	204

Primary outcome: Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss

Time frame: 24 weeks after end of treatment (EOT). Number. Unit: Participants

Measure	PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks n = 225	PEG 1.5 mcg/kg QW * 24 Weeks n = 221	PEG 1.5 mcg/kg QW * 48 Weeks n = 224
Value	39	40	70

PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks vs PEG 1.5 mcg/kg QW * 24 Weeks: Pairwise rate difference: 0.008 (95% CI -0.063 to 0.079), p = 0.860, Cochran-Mantel-Haenszel
PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks vs PEG 1.5 mcg/kg QW * 48 Weeks: Pairwise rate difference: 0.139 (95% CI 0.061 to 0.217), p <0.001, Cochran-Mantel-Haenszel
PEG 1.5 mcg/kg QW * 24 Weeks vs PEG 1.5 mcg/kg QW * 48 Weeks: Pairwise rate difference: -0.132 (90% CI -0.198 to -0.065)

Population analysed: Treated participants

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PEG 1.0 mcg/kg QW x24 Weeks	10 of 225 (4.4%)	173 of 225 (76.9%)	Not reported
PEG 1.5 mcg/kg QW x24 Weeks	11 of 221 (5%)	169 of 221 (76.5%)	Not reported
PEG 1.5 mcg/kg QW x48 Weeks	15 of 224 (6.7%)	182 of 224 (81.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25200354Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, Ren H, Ding H, Sheng J, Wei L, Chen S, Fan X, Huang W, Pan C, Gao Z, Zhang J, Zhou B, Chen G, Wan M, Tang H, Wang G, Yang Y, Mohamed R, Guan R, Lee TH, Chang WH, Zhenfei H, Ye Z, Xu D. Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial. J Clin Virol. 2014 Dec;61(4):509-16. doi: 10.1016/j.jcv.2014.08.008. Epub 2014 Aug 18.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

Related trials for Hepatitis B, Chronic

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
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Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pegylated interferon alpha-2b in people with Hepatitis B, Chronic, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss (time frame: 24 weeks after end of treatment (EOT)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00536263, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2017.