Trial Outcomes & Findings for Efficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603) (NCT NCT00686790)

Last Updated: 2017-04-06

Results Overview

For virological response, a participant was defined as a responder if his/her serum sample tested negative for Hepatitis D Virus - ribonucleic acid (HDV-RNA) by polymerase chain reaction (PCR) at end of treatment (EOT).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation

Results posted on

2017-04-06

Participant Flow

Of the enrolled participants, 19 received no study medication and 1 was not eligible. The Intent-to-Treat (ITT) population is 48.

Participant milestones

Participant milestones
Measure	PegIntron Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Overall Study STARTED	48
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	PegIntron Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1
Overall Study Death	1
Overall Study Lost to Follow-up	12

Baseline Characteristics

Efficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PegIntron n=48 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Age, Continuous	37.55 years STANDARD_DEVIATION 12.48 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Region of Enrollment Romania	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: 52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation

Population: The population analyzed excludes participants that were not administered any study medication and had protocol violations. 2 participants with adverse events (AE) that had protocol violations have been included in the analysis.

Outcome measures

Outcome measures
Measure	PegIntron n=36 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Number of Participants With a Virological Response Responders at 52 weeks	12 Participants
Number of Participants With a Virological Response Non-responders at 52 weeks	24 Participants
Number of Participants With a Virological Response Responders at 104 weeks	9 Participants
Number of Participants With a Virological Response Non-responders at 104 weeks	27 Participants

PRIMARY outcome

Timeframe: 52 weeks (EOT), 104 weeks (EOF)

Population: The population analyzed excluded participants that were not administered study medication, had protocol violations and those for whom ALT values were not available. 2 participants with adverse events (AE) that had protocol violations have been included in the analysis.

A participant was defined as a responder if his alanine aminotransferase (ALT) level after 52 weeks, i.e. at EOT, was below the upper reference range as specified by Bioclinica. The normal reference range for ALT is 5-55 U/L.

Outcome measures

Outcome measures
Measure	PegIntron n=32 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Number of Participants With a Biochemical Response Responders at 52 weeks	18 Participants
Number of Participants With a Biochemical Response Non-responders at 52 weeks	14 Participants
Number of Participants With a Biochemical Response Responders at 104 weeks	9 Participants
Number of Participants With a Biochemical Response Non-responders at 104 weeks	23 Participants

PRIMARY outcome

Timeframe: 52 weeks (EOT), 104 weeks (EOF)

The combined response was defined as an ALT level below the upper reference range and a negative HDV-RNA test. The normal reference range for ALT is 5-55 U/L.

Outcome measures

Outcome measures
Measure	PegIntron n=32 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Number of Participants With a Combined Response Responders at 52 weeks	7 Participants
Number of Participants With a Combined Response Non-responders at 52 weeks	25 Participants
Number of Participants With a Combined Response Responders at 104 weeks	6 Participants
Number of Participants With a Combined Response Non-responders at 104 weeks	26 Participants

SECONDARY outcome

Timeframe: 52 week (EOT)

Serum samples collected from the participants were tested by PCR to detect HBV-DNA. HBV response was defined as the absence of HBV-deoxyribonucleic acid (HBV-DNA) in serum.

Outcome measures

Outcome measures
Measure	PegIntron n=36 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) Responders	6 Participants
Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) Non responders	30 Participants

SECONDARY outcome

Timeframe: Baseline and 52 week (EOT)

The liver histology response was defined as at least a 2 point decrease in the necrosis inflammation score (a sum of periportal necrosis \[0-10\], lobular inflammation \[0-4\], portal inflammation \[0-4\], with the total score of 18 representing the worst outcome) and no increase or regression of fibrosis (scored \[0-4\]) in the pre- and post-treatment liver biopsies. The efficacy of treatment based on histological response was assessed by the investigator as complete response, partial response, minimal response, progressive disease, and not assessable at EOT.

Outcome measures

Outcome measures
Measure	PegIntron n=36 Participants Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Number of Participants With a Liver Histology Response Complete response	10 Participants
Number of Participants With a Liver Histology Response Partial response	14 Participants
Number of Participants With a Liver Histology Response Minimal response	6 Participants
Number of Participants With a Liver Histology Response Progressive disease	3 Participants
Number of Participants With a Liver Histology Response Response not assessable	3 Participants

Adverse Events

PegIntron

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PegIntron n=49 participants at risk Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Gastrointestinal disorders PANCREATITIS	2.0% 1/49 • Number of events 1 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders PYREXIA	2.0% 1/49 • Number of events 1 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Investigations ALANINE AMINOTRANSFERASE INCREASED	2.0% 1/49 • Number of events 1 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	2.0% 1/49 • Number of events 1 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Respiratory, thoracic and mediastinal disorders INTERSTITIAL LUNG DISEASE	2.0% 1/49 • Number of events 1 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.

Other adverse events

Other adverse events
Measure	PegIntron n=49 participants at risk Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks
Ear and labyrinth disorders VERTIGO	18.4% 9/49 • Number of events 86 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Eye disorders VISION BLURRED	6.1% 3/49 • Number of events 15 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders ABDOMINAL PAIN	18.4% 9/49 • Number of events 32 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	6.1% 3/49 • Number of events 3 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders DIARRHOEA	10.2% 5/49 • Number of events 7 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders DRY MOUTH	6.1% 3/49 • Number of events 11 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders GINGIVAL BLEEDING	8.2% 4/49 • Number of events 8 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders NAUSEA	36.7% 18/49 • Number of events 94 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Gastrointestinal disorders VOMITING	14.3% 7/49 • Number of events 20 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders ASTHENIA	32.7% 16/49 • Number of events 76 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders CHEST PAIN	8.2% 4/49 • Number of events 13 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders CHILLS	65.3% 32/49 • Number of events 187 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders FATIGUE	53.1% 26/49 • Number of events 135 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders INFLUENZA LIKE ILLNESS	8.2% 4/49 • Number of events 21 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders IRRITABILITY	14.3% 7/49 • Number of events 24 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
General disorders PYREXIA	77.6% 38/49 • Number of events 310 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Metabolism and nutrition disorders ANOREXIA	28.6% 14/49 • Number of events 43 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Musculoskeletal and connective tissue disorders ARTHRALGIA	44.9% 22/49 • Number of events 231 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Musculoskeletal and connective tissue disorders BACK PAIN	8.2% 4/49 • Number of events 4 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Musculoskeletal and connective tissue disorders BONE PAIN	10.2% 5/49 • Number of events 56 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Musculoskeletal and connective tissue disorders MYALGIA	65.3% 32/49 • Number of events 253 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Nervous system disorders DIZZINESS	30.6% 15/49 • Number of events 94 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Nervous system disorders HEADACHE	77.6% 38/49 • Number of events 674 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Nervous system disorders SOMNOLENCE	10.2% 5/49 • Number of events 26 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Psychiatric disorders ANGER	10.2% 5/49 • Number of events 15 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Psychiatric disorders DEPRESSION	6.1% 3/49 • Number of events 5 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Psychiatric disorders INSOMNIA	12.2% 6/49 • Number of events 10 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	6.1% 3/49 • Number of events 3 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	12.2% 6/49 • Number of events 21 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Skin and subcutaneous tissue disorders ALOPECIA	16.3% 8/49 • Number of events 15 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Skin and subcutaneous tissue disorders ERYTHEMA	6.1% 3/49 • Number of events 7 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.
Skin and subcutaneous tissue disorders PRURITUS	8.2% 4/49 • Number of events 24 Adverse events are reported for all 48 participants that received study medication and included the ITT population, as well as one participant that was identified to be ineligible for the study after enrollment.

Additional Information

Vice President of Late Stage Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 30 days from the time submitted to the sponsor for review.
Publication restrictions are in place

Restriction type: OTHER