Trial Outcomes & Findings for Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137) (NCT NCT00686517)
NCT ID: NCT00686517
Last Updated: 2017-04-05
Results Overview
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.
COMPLETED
PHASE3
130 participants
Evaluated at the end of 6 months
2017-04-05
Participant Flow
130 participants were randomized to pegylated-interferon alpha-2b at the dose of 1.5 mcg/kg/week for 24 weeks (PEG-IFN 24), pegylated-interferon alpha-2b at the dose of 1.5 mcg/kg/week for 12 weeks (PEG-IFN 12), or pegylated-interferon alpha-2b at the dose of 1.5 mcg/kg/week + ribavirin at the dose of 10.6 mg/kg/day for 12 weeks (PEG-IFN + RVB 12).
Participant milestones
| Measure |
PEG-IFN 24
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Treatment
STARTED
|
44
|
43
|
43
|
|
Treatment
Completed Final Treatment Visit
|
44
|
43
|
43
|
|
Treatment
COMPLETED
|
38
|
40
|
42
|
|
Treatment
NOT COMPLETED
|
6
|
3
|
1
|
|
Follow-up
STARTED
|
37
|
38
|
39
|
|
Follow-up
COMPLETED
|
29
|
28
|
29
|
|
Follow-up
NOT COMPLETED
|
8
|
10
|
10
|
Reasons for withdrawal
| Measure |
PEG-IFN 24
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Treatment
Serious Adverse Event
|
1
|
2
|
1
|
|
Treatment
Adverse Event
|
2
|
0
|
0
|
|
Treatment
Poor Protocol Compliance
|
1
|
0
|
0
|
|
Treatment
Protocol Violation
|
2
|
1
|
0
|
Baseline Characteristics
Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137)
Baseline characteristics by cohort
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
Total
n=130 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.55 years
STANDARD_DEVIATION 13.86 • n=5 Participants
|
38.32 years
STANDARD_DEVIATION 13.95 • n=7 Participants
|
38.52 years
STANDARD_DEVIATION 12.48 • n=5 Participants
|
37.79 years
STANDARD_DEVIATION 13.37 • n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
93 Participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
44 participants
n=5 Participants
|
43 participants
n=7 Participants
|
43 participants
n=5 Participants
|
130 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Evaluated at the end of 6 monthsPopulation: Intent-to-treat population (ITT): including all randomized participants who received at least one dose of study medication. Participants without measurements at the end of treatment or who discontinued the study for any reason before the end of the treatment were considered as non-responders.
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.
Outcome measures
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period
|
23 participants
|
20 participants
|
21 participants
|
SECONDARY outcome
Timeframe: At the end of treatment (either 12 weeks or 24 weeks depending on randomization).Population: Intent-to-treat population (ITT): including all randomized participants who received at least one dose of study medication. Participants without measurements at the end of treatment or who discontinued the study for any reason before the end of the treatment were considered as non-responders.
ETR was achieved if serum HCV RNA level at the end of 12 or 24 weeks treatment (depending on treatment arm) was \<15 IU/mL.
Outcome measures
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Virologic Response at the End of Treatment Follow-up (ETR)
|
26 participants
|
28 participants
|
27 participants
|
SECONDARY outcome
Timeframe: At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization).Population: Intent-to-treat population (ITT): including all randomized participants who received at least one dose of study medication. Participants without measurements at the end of treatment or who discontinued the study for any reason before the end of the treatment were considered as non-responders.
LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was \<15 IU/mL.
Outcome measures
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).
|
20 participants
|
19 participants
|
19 participants
|
SECONDARY outcome
Timeframe: Evaluated at end of treatment (either 12 weeks or 24 weeks, depending on randomization), at 6-month follow-up visit, or at 12-month follow-up visit.Population: Intent-to-treat population (ITT): including all randomized participants who received at least one dose of study medication. Participants without measurements at the end of treatment or who discontinued the study for any reason before the end of the treatment were considered as non-responders.
ALT normalization was used as a measure of biochemical response to treatment. ALT levels were assessed at each study visit by the local laboratory, and efficacy measurements at the end of treatment, at 6 and 12 months post treatment follow-up were reported.
Outcome measures
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
12-month Follow-up Period
|
27 participants
|
23 participants
|
23 participants
|
|
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
End of Treatment
|
28 participants
|
31 participants
|
32 participants
|
|
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
6-month Follow-up Period
|
31 participants
|
27 participants
|
28 participants
|
SECONDARY outcome
Timeframe: Evaluated at 2 and 4 weeks of treatmentPopulation: Intent-to-treat population (ITT): including all randomized participants who received at least one dose of study medication. Participants without measurements at the end of treatment or who discontinued the study for any reason before the end of the treatment were considered as non-responders.
Participants were considered to have RVR if serum HCV RNA level at 2 or 4 weeks of treatment was below the cut off value of the referring local laboratory of each participating site.
Outcome measures
| Measure |
PEG-IFN 24
n=44 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN + RVB 12
n=43 Participants
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Number of Participants With Rapid Virologic Response (RVR)
2 weeks after start of treatment
|
24 participants
|
25 participants
|
23 participants
|
|
Number of Participants With Rapid Virologic Response (RVR)
4 weeks after start of treatment
|
28 participants
|
35 participants
|
34 participants
|
SECONDARY outcome
Timeframe: Treatment Weeks 2, 4, 8, and 12Population: The association between HCV specific immune and SR to be assessed applying descriptive methods could not be evaluated as PBMC measurements were not carried out.
Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12.
Outcome measures
Outcome data not reported
Adverse Events
PEG-IFN 12
PEG-IFN 24
PEG-IFN + RVB 12
Serious adverse events
| Measure |
PEG-IFN 12
n=43 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN 24
n=44 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN + RVB 12
n=43 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Ear and labyrinth disorders
HypoAcusis
|
2.3%
1/43 • Number of events 1
|
0.00%
0/44
|
0.00%
0/43
|
|
Endocrine disorders
Autoimmune thyroiditis
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Dacryocystitis
|
0.00%
0/43
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Wound Infection
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
|
Investigations
Transaminases Increased
|
2.3%
1/43 • Number of events 1
|
0.00%
0/44
|
0.00%
0/43
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
|
0.00%
0/43
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
|
Nervous system disorders
Headache
|
2.3%
1/43 • Number of events 1
|
0.00%
0/44
|
0.00%
0/43
|
|
Nervous system disorders
Optic Neuritis
|
0.00%
0/43
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
|
Psychiatric disorders
Mania
|
0.00%
0/43
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
|
Psychiatric disorders
Pyschotic Disorder
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
Other adverse events
| Measure |
PEG-IFN 12
n=43 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
|
PEG-IFN 24
n=44 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
|
PEG-IFN + RVB 12
n=43 participants at risk
Pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin 10.6 mg/kg/day for 12 weeks
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
9.3%
4/43 • Number of events 4
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
51.2%
22/43 • Number of events 25
|
72.7%
32/44 • Number of events 44
|
60.5%
26/43 • Number of events 34
|
|
Blood and lymphatic system disorders
Leukopenia
|
72.1%
31/43 • Number of events 36
|
68.2%
30/44 • Number of events 45
|
72.1%
31/43 • Number of events 37
|
|
Blood and lymphatic system disorders
Neutropenia
|
14.0%
6/43 • Number of events 7
|
6.8%
3/44 • Number of events 3
|
4.7%
2/43 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/43
|
9.1%
4/44 • Number of events 4
|
4.7%
2/43 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/43
|
2.3%
1/44 • Number of events 1
|
7.0%
3/43 • Number of events 3
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/43
|
6.8%
3/44 • Number of events 3
|
0.00%
0/43
|
|
Gastrointestinal disorders
Dyspepsia
|
9.3%
4/43 • Number of events 4
|
0.00%
0/44
|
7.0%
3/43 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
4.7%
2/43 • Number of events 2
|
15.9%
7/44 • Number of events 9
|
7.0%
3/43 • Number of events 4
|
|
General disorders
Asthenia
|
27.9%
12/43 • Number of events 12
|
25.0%
11/44 • Number of events 11
|
16.3%
7/43 • Number of events 7
|
|
General disorders
Chills
|
9.3%
4/43 • Number of events 4
|
2.3%
1/44 • Number of events 1
|
14.0%
6/43 • Number of events 6
|
|
General disorders
Irritability
|
4.7%
2/43 • Number of events 2
|
9.1%
4/44 • Number of events 4
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Pain
|
18.6%
8/43 • Number of events 8
|
20.5%
9/44 • Number of events 9
|
16.3%
7/43 • Number of events 8
|
|
General disorders
Pyrexia
|
62.8%
27/43 • Number of events 31
|
68.2%
30/44 • Number of events 35
|
65.1%
28/43 • Number of events 34
|
|
Investigations
Hemoglobin Decreased
|
2.3%
1/43 • Number of events 1
|
15.9%
7/44 • Number of events 7
|
11.6%
5/43 • Number of events 5
|
|
Investigations
Platelet Count Decreased
|
16.3%
7/43 • Number of events 7
|
11.4%
5/44 • Number of events 6
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Transaminases Increased
|
9.3%
4/43 • Number of events 4
|
18.2%
8/44 • Number of events 9
|
4.7%
2/43 • Number of events 2
|
|
Investigations
Weight Decreased
|
0.00%
0/43
|
9.1%
4/44 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
2.3%
1/43 • Number of events 1
|
15.9%
7/44 • Number of events 7
|
2.3%
1/43 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.6%
11/43 • Number of events 15
|
29.5%
13/44 • Number of events 14
|
30.2%
13/43 • Number of events 13
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.3%
1/43 • Number of events 1
|
6.8%
3/44 • Number of events 3
|
9.3%
4/43 • Number of events 4
|
|
Nervous system disorders
Headache
|
25.6%
11/43 • Number of events 11
|
29.5%
13/44 • Number of events 15
|
27.9%
12/43 • Number of events 14
|
|
Psychiatric disorders
Anxiety
|
2.3%
1/43 • Number of events 1
|
4.5%
2/44 • Number of events 2
|
7.0%
3/43 • Number of events 3
|
|
Psychiatric disorders
Depression
|
4.7%
2/43 • Number of events 2
|
13.6%
6/44 • Number of events 6
|
11.6%
5/43 • Number of events 6
|
|
Psychiatric disorders
Insomia
|
2.3%
1/43 • Number of events 1
|
11.4%
5/44 • Number of events 5
|
7.0%
3/43 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.3%
4/43 • Number of events 4
|
15.9%
7/44 • Number of events 7
|
4.7%
2/43 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythrema
|
0.00%
0/43
|
6.8%
3/44 • Number of events 4
|
7.0%
3/43 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.3%
1/43 • Number of events 1
|
2.3%
1/44 • Number of events 1
|
9.3%
4/43 • Number of events 6
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator agrees not to publish or publish or present any results of the study without the prior written permission of Schering-Plough The principal investigator further agrees to allow the Sponsor to review, 30 days prior to submission for publication or presentation, copies of abstracts or manuscripts for publication (including texts of oral presentations) which report any results of the study.
- Publication restrictions are in place
Restriction type: OTHER