Hepatitis B, ChronicPhase 3NCT01641926

A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)

A Phase 3 study testing PEG-Intron™ and PEGASYS™ in people with Hepatitis B, Chronic, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

This study is being done to compare the safety and efficacy of PEG-Intron™ to that of PEGASYS™ in participants with chronic hepatitis B (hepatitis B envelope antigen [HBeAg] positive or negative) who have not previously been treated with interferon. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: PEG-Intron™ and PEGASYS™
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 402 participants
Where: No sites listed yet
Study dates: 26 Nov 2012to 21 Jan 2016
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Must be able to adhere to dose and visit schedules
≥ 40 kg
Hepatitis B surface antigen (HBsAg) positive for at least 6 months
Anti-HBs negative
Female participants of childbearing potential must agree to use an acceptable
method of contraception from at least 2 weeks prior to Day 1 and continue until at least 1 month after last dose of study drug

Show all 10Show fewer

HBeAg(+)
Anti-HBe(-)
HBeAg(-)
Anti-HBe(+)

Who cannot join

Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus
Prior treatment with interferon for hepatitis B
Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study
Use of any investigational drug within 30 days of the screening visit
Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1
Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy

Show all 15Show fewer

Diabetic and/or hypertensive with clinically significant ocular examination findings
History of stroke or transient ischemic attack
Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder)
Chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis)
Current or history of any clinically significant cardiac abnormalities/dysfunction
Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
Myelodysplastic syndromes
Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
Pregnant or nursing, or intending to become pregnant during the trial period

About this study

Official title: A Multicenter Open-label Study to Evaluate the Safety and Efficacy of PEG-Intron™ Versus PEGASYS™ in Subjects With HBeAg Positive Chronic Hepatitis B and HBeAg Negative Chronic Hepatitis B Protocol No. MK-4031-376-00 (Also Known as SCH 054031, P08450)

Conditions: Hepatitis B, Chronic
Being tested: PEG-Intron™, PEGASYS™
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.

PEG-Intron™Biological
Also called SCH 054031, Pegylated interferon alfa-2b
PEG-Intron subcutaneously (SC) once weekly for a total of 48 weeks
PEGASYS™Biological
Also called Pegylated interferon alfa-2a
PEGASYS subcutaneously (SC) once weekly for a total of 48 weeks

Study groups in NCT01641926
Study group	Role	What they receive
HBeAg(+) PEG-Intron	Experimental	HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks. Receives: Biological: PEG-Intron™
HBeAg(+) PEGASYS	Active comparator	HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks. Receives: Biological: PEGASYS™
HBeAg(-) PEG-Intron	Experimental	HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks. Receives: Biological: PEG-Intron™
HBeAG(-) PEGASYS	Active comparator	HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks. Receives: Biological: PEGASYS™

What is being measured

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

Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment
Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg.
Measured: FU Week 24 (Study Week 72)
Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment
The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.
Measured: FU Week 24 (Study Week 72)

Secondary outcomes (3)

Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.
Measured: FU Week 24 (Study Week 72)
Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment
ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported.
Measured: FU Week 24 (Study Week 72)
Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels <2000 IU/mL at 24 weeks post-treatment was reported.
Measured: FU Week 24 (Study Week 72)

Timeline

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

26 Nov 201221 Jan 2016

First posted17 Jul 2012 (estimated)
Study start26 Nov 2012
Primary completion21 Jan 2016
Study completion21 Jan 2016

Why it stopped: This study was terminated early due to poor recruitment

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.
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: 402 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01641926
Sponsor's protocol ID: P08450
Other IDs: MK-4031-376
Status last verified: Jul 2018
First submitted: 11 Jul 2012
Last updated: 27 Aug 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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 27 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter Open-label Study to Evaluate the Safety and Efficacy of PEG-Intron™ Versus PEGASYS™ in Subjects With HBeAg Positive Chronic Hepatitis B and HBeAg Negative Chronic Hepatitis B Protocol No. MK-4031-376-00 (Also Known as SCH 054031, P08450)
ClinicalTrials.gov ID: NCT01641926
Acronym / sponsor ID: P08450
Conditions: Hepatitis B, Chronic
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: This study was terminated early due to poor recruitment
Enrolment: 402 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 26 Nov 2012 (actual)
Primary completion: 21 Jan 2016 (actual)
Study completion: 21 Jan 2016 (actual)
First posted: 17 Jul 2012 (estimated)
Results: Posted 12 Jan 2017

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: 4

Arm	Type	Receives
HBeAg(+) PEG-Intron	Experimental	Biological: PEG-Intron™HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks.
HBeAg(+) PEGASYS	Active comparator	Biological: PEGASYS™HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.
HBeAg(-) PEG-Intron	Experimental	Biological: PEG-Intron™HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks.
HBeAG(-) PEGASYS	Active comparator	Biological: PEGASYS™HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.

Who may qualify

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

Key inclusion criteria (10 listed)

Must be able to adhere to dose and visit schedules
≥ 40 kg
Hepatitis B surface antigen (HBsAg) positive for at least 6 months
Anti-HBs negative
Female participants of childbearing potential must agree to use an acceptable

Key exclusion criteria (15 listed)

Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus
Prior treatment with interferon for hepatitis B
Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study
Use of any investigational drug within 30 days of the screening visit
Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1

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
PEG-Intron™Also: SCH 054031, Pegylated interferon alfa-2bPEG-Intron subcutaneously (SC) once weekly for a total of 48 weeks	Biological	HBeAg(+) PEG-Intron, HBeAg(-) PEG-Intron
PEGASYS™Also: Pegylated interferon alfa-2aPEGASYS subcutaneously (SC) once weekly for a total of 48 weeks	Biological	HBeAG(-) PEGASYS, HBeAg(+) PEGASYS

Primary outcome

Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment
Time frame: FU Week 24 (Study Week 72)
Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg.
Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment
Time frame: FU Week 24 (Study Week 72)
The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported.

3 secondary outcomes

Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
Time frame: FU Week 24 (Study Week 72)
Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment
Time frame: FU Week 24 (Study Week 72)
Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
Time frame: FU Week 24 (Study Week 72)

Results and safety

Results posted to the registry on 12 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HBeAg(+) PEG-Intron	143	115
HBeAg(+) PEGASYS	145	130
HBeAg(-) PEG-Intron	57	46
HBeAg(-) PEGASYS	57	53

Primary outcome: Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment

Time frame: FU Week 24 (Study Week 72). Number. Unit: percentage of participants

Measure	HBeAg(+) PEG-Intron n = 142	HBeAg(+) PEGASYS n = 144	HBeAg(-) PEG-Intron n = 0	HBeAg(-) PEGASYS n = 0
Value	25.4	23.6	–	–

HBeAg(+) PEG-Intron vs HBeAg(+) PEGASYS: Adjusted Treatment Difference: 1.6 (95% CI -8.4 to 11.6)

Population analysed: All randomized HBeAg(+) participants who received ≥1 dose of study medication. HBeAg(-) participants were not analyzed for HBeAg seroconversion.

Primary outcome: Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment

Time frame: FU Week 24 (Study Week 72). Number. Unit: percentage of participants

Measure	HBeAg(+) PEG-Intron n = 0	HBeAg(+) PEGASYS n = 0	HBeAg(-) PEG-Intron n = 56	HBeAg(-) PEGASYS n = 57
Value	–	–	30.4	33.3

HBeAg(-) PEG-Intron vs HBeAg(-) PEGASYS: Adjusted Treatment Difference: -3.0 (95% CI -20.2 to 14.3)

Population analysed: All randomized HBeAg(-) participants who received ≥1 dose of study medication. HBeAg(+) participants were not included in this analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs up to 30 days after Week 24 Post-Treatment Visit (up to 76 weeks) Nonserious AEs up to Treatment Week 48 (up to 48 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HBeAg(+) PEG-Intron	12 of 142 (8.5%)	126 of 142 (88.7%)	Not reported
HBeAg(+) PEGASYS	10 of 144 (6.9%)	124 of 144 (86.1%)	Not reported
HBeAg(-) PEG-Intron	1 of 56 (1.8%)	50 of 56 (89.3%)	Not reported
HBeAG(-) PEGASYS	2 of 57 (3.5%)	50 of 57 (87.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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
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

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.

Study Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PEG-Intron™ and PEGASYS™ 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 10 inclusion and 15 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: stopped early, as of the sponsor's last update on 27 Aug 2018. 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 12 Jan 2017). 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?

Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment (time frame: FU Week 24 (Study Week 72)). The study lists 2 primary outcomes in all. 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 NCT01641926.

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 27 Aug 2018.