Hepatitis C, Chronic
Conditions
Brief summary
Study P02538 Part 2 is a 5-year long term follow-up (LTFU) study in pediatric participants who were treated with at least one dose of peginterferon alfa-2b (PEG-IFN) and ribavirin (RBV) and who completed the follow-up in the P02538 Part 1 study (NCT00104052). No study drug therapy will be administered during the P02538 Part 2 study. Durability of virologic response will be assessed for participants who attained sustained virologic response (SVR) in Part I of this study by performing annual Hepatitis C Virus ribonucleic acid (HCV-RNA) testing. In addition, this study will characterize long-term safety in all participants who received PEG-IFN plus RBV treatment.
Detailed description
During the Part 2 LTFU, participants will be evaluated at Years 1, 2, 3, 4, and 5. Each participant's first LTFU visit will be scheduled approximately 1 year after the post-treatment Follow-up Week 24 visit in Part 1 of this study (NCT00104052).
Interventions
BIOLOGICALPeginterferon alfa-2b
In the previous treatment protocol (P02538 Part 1), peginterferon alfa-2b was administered at a dose of 60 μg/m\^2 by subcutaneous injection weekly for up to 48 weeks. No treatment was administered on the current follow-up study (P02538 Part 2).
DRUGRibavirin
In the previous treatment protocol (P02538 Part 1), ribavirin was administered at a dose of 15 mg/kg/day orally in two divided doses for up to 48 weeks. No treatment was administered on the current follow-up study (P02538 Part 2).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent must be obtained from the participant or the participant's parent or legal guardian prior to any long-term follow-up study-related procedures. According to local laws and/or IRB/IEC requirements, participants may also need to provide written assent. * The participant must have received at least one dose of peginterferon alfa-2b and ribavirin in the Protocol No. P02538 study. * The participant must have completed the 24-week post-treatment follow-up in the P02538 Part 1 study. All participants whether sustained responders, relapsers, or nonresponders are eligible to participate.
Exclusion criteria
* Concurrent participation in any other clinical study. * Retreatment with any antiviral or immunomodulatory drug for chronic hepatitis C after completion of, or discontinuation from, the treatment phase of the P02538 Part 1 study. * Any condition that in the opinion of the Investigator would make the participant unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Relapsed At End of LTFU Year 5 | Part 2 LTFU Year 5 | Relapse was defined as Hepatitis C Virus ribonucleic acid (HCV-RNA) that was above the lower limit of quantitation at Year 5 of the LTFU. |
| Mean Height Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years) | To determine long-term effects of the Part 1 treatment on height, changes in height during the Part 2 LTFU were evaluated using height percentiles based on 2000 Center For Disease Control growth charts for the general population. |
| Mean Weight Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years) | To determine long-term effects of the Part 1 treatment on weight, changes in weight during the Part 2 LTFU were evaluated using weight percentiles based on 2000 Center For Disease Control growth charts for the general population. |
| Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years) | To determine long-term effects of the Part 1 treatment on BMI, changes in BMI during the Part 2 LTFU were evaluated using BMI percentiles based on 2000 Center For Disease Control growth charts for the general population. |
| Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Last assessment of the Part 2 LTFU (up to 5 years) | The Tanner Stage (TS) defines physical measurements of sexual development based on external primary and secondary sex characteristics. Female participants are evaluated for breast development and pubic hair distribution and male participants are evaluated for genital development and pubic hair distribution, based on a 5-stage ordinal scale ranging from TS 1 (prepubertal/preadolescent characteristics) to TS 5 (mature or adult characteristics). Mean ages for attaining each TS in the normal population have been previously established based on measuring correlating reproductive hormone levels, and are expressed in years as follows for females (F) and males (M): TS 1= 7.1 (F+M); TS 2= 10.5 (F), 12.1 (M); TS 3= 11.6 (F), 13.6 (M); TS 4=, 12.3 (F), 15.1 (M); TS 5= 14.5 (F), 18 (M). To assess sexual maturation at the end of the LTFU (last observation), females and males were staged and the mean age at each TS attained was reported. |
Participant flow
Pre-assignment details
Of 107 participants who enrolled in Part 1 of this study and were potentially eligible for the Part 2 Long Term Follow-up (LTFU), 94 participants enrolled in the current LTFU study (Part 2).
Participants by arm
| Arm | Count |
|---|---|
| PEG-IFN + RBV: LTFU Pediatric participants who completed treatment with peginterferon alfa-2b (PEG-IFN) plus ribavirin (RBV) in P02538 Part 1 of this study (NCT00104052) were enrolled in a 5-year Long Term Follow-Up (LTFU) during P02538 Part 2 (NCT00761735). No study treatment was administered in Part 2. | 94 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative | 1 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Non-compliance with protocol | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | PEG-IFN + RBV: LTFU |
|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 3.9 |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 3 / 94 |
Outcome results
Primary
Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender
The Tanner Stage (TS) defines physical measurements of sexual development based on external primary and secondary sex characteristics. Female participants are evaluated for breast development and pubic hair distribution and male participants are evaluated for genital development and pubic hair distribution, based on a 5-stage ordinal scale ranging from TS 1 (prepubertal/preadolescent characteristics) to TS 5 (mature or adult characteristics). Mean ages for attaining each TS in the normal population have been previously established based on measuring correlating reproductive hormone levels, and are expressed in years as follows for females (F) and males (M): TS 1= 7.1 (F+M); TS 2= 10.5 (F), 12.1 (M); TS 3= 11.6 (F), 13.6 (M); TS 4=, 12.3 (F), 15.1 (M); TS 5= 14.5 (F), 18 (M). To assess sexual maturation at the end of the LTFU (last observation), females and males were staged and the mean age at each TS attained was reported.
Time frame: Last assessment of the Part 2 LTFU (up to 5 years)
Population: All participants enrolled in the P02538 Part 2 LTFU with non-missing Tanner Stage data at the last observation (up to Year 5 of the LTFU) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PEG-IFN + RBV: LTFU (All) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 2 participants (n=5, n=3) | 11.86 years | Standard Deviation 0.78 |
| PEG-IFN + RBV: LTFU (All) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 4 participants (n=4, n=6) | 16.00 years | Standard Deviation 4.31 |
| PEG-IFN + RBV: LTFU (All) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 3 participants (n=7, n=1) | 15.26 years | Standard Deviation 4.64 |
| PEG-IFN + RBV: LTFU (All) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 5 participants (n=21, n=27) | 17.37 years | Standard Deviation 2.71 |
| PEG-IFN + RBV: LTFU (All) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 1 participants (n=4, n=5) | 9.75 years | Standard Deviation 1.13 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 5 participants (n=21, n=27) | 19.18 years | Standard Deviation 2.48 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 1 participants (n=4, n=5) | 11.00 years | Standard Deviation 0.8 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 2 participants (n=5, n=3) | 12.53 years | Standard Deviation 1.27 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 3 participants (n=7, n=1) | 13.60 years | Standard Deviation 0 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender | Age of TS 4 participants (n=4, n=6) | 14.75 years | Standard Deviation 1.47 |
Primary
Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU
To determine long-term effects of the Part 1 treatment on BMI, changes in BMI during the Part 2 LTFU were evaluated using BMI percentiles based on 2000 Center For Disease Control growth charts for the general population.
Time frame: Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)
Population: All participants enrolled in the P02538 Part 2 LTFU were evaluated in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 48.11 percentile | Standard Deviation 29.59 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 48.44 percentile | Standard Deviation 30.46 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 51.15 percentile | Standard Deviation 30.27 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 48.61 percentile | Standard Deviation 29.72 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 52.14 percentile | Standard Deviation 31 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 48.79 percentile | Standard Deviation 29.4 |
| PEG-IFN + RBV: LTFU (All) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 50.4 percentile | Standard Deviation 29.63 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 55.38 percentile | Standard Deviation 31.48 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 59.76 percentile | Standard Deviation 31.52 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 59.91 percentile | Standard Deviation 31.55 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 52.89 percentile | Standard Deviation 30.82 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 54.96 percentile | Standard Deviation 30.89 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 48.69 percentile | Standard Deviation 31.52 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 52.34 percentile | Standard Deviation 31.87 |
Primary
Mean Height Percentiles of Participants Over LTFU
To determine long-term effects of the Part 1 treatment on height, changes in height during the Part 2 LTFU were evaluated using height percentiles based on 2000 Center For Disease Control growth charts for the general population.
Time frame: Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)
Population: All participants enrolled in the P02538 Part 2 LTFU were evaluated in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 50.56 percentile | Standard Deviation 29.18 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 49.62 percentile | Standard Deviation 30.87 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 49.21 percentile | Standard Deviation 29.03 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 47.61 percentile | Standard Deviation 29.57 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 48.05 percentile | Standard Deviation 28.38 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 45.96 percentile | Standard Deviation 30.45 |
| PEG-IFN + RBV: LTFU (All) | Mean Height Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 48.94 percentile | Standard Deviation 27.38 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 43.56 percentile | Standard Deviation 27.19 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 52.5 percentile | Standard Deviation 29.98 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 43.37 percentile | Standard Deviation 27.87 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 46.24 percentile | Standard Deviation 29.19 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 46.00 percentile | Standard Deviation 28.24 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 45.27 percentile | Standard Deviation 29.44 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Height Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 43.51 percentile | Standard Deviation 27.57 |
Primary
Mean Weight Percentiles of Participants Over LTFU
To determine long-term effects of the Part 1 treatment on weight, changes in weight during the Part 2 LTFU were evaluated using weight percentiles based on 2000 Center For Disease Control growth charts for the general population.
Time frame: Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)
Population: All participants enrolled in the P02538 Part 2 LTFU were evaluated in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 53.62 percentile | Standard Deviation 26.75 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 51.75 percentile | Standard Deviation 28.9 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 52.5 percentile | Standard Deviation 26.83 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 51.16 percentile | Standard Deviation 27.16 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 51.73 percentile | Standard Deviation 26.89 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 50.15 percentile | Standard Deviation 28.44 |
| PEG-IFN + RBV: LTFU (All) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 53.18 percentile | Standard Deviation 29.12 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | Last Available LTFU Visit (n=46, n=48) | 55.53 percentile | Standard Deviation 30.67 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | Part 1 Pre-treatment Baseline | 58.56 percentile | Standard Deviation 30.56 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 1 (n=40, n=44) | 56.38 percentile | Standard Deviation 30.55 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 3 (n=39, n=44) | 54.26 percentile | Standard Deviation 30.37 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 4 (n=40, n=38) | 49.50 percentile | Standard Deviation 30.37 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 5 (n=38, n=42) | 53.12 percentile | Standard Deviation 31.38 |
| PEG-IFN + RBV: LTFU (48 Weeks) | Mean Weight Percentiles of Participants Over LTFU | LTFU Year 2 (n=39, n=39) | 52.03 percentile | Standard Deviation 30.47 |
Primary
Number of Participants Who Relapsed At End of LTFU Year 5
Relapse was defined as Hepatitis C Virus ribonucleic acid (HCV-RNA) that was above the lower limit of quantitation at Year 5 of the LTFU.
Time frame: Part 2 LTFU Year 5
Population: Of 94 participants entering the P02538 Part 2 LTFU, 63 participants had achieved sustained virologic response (SVR) while in Part 1 of the study. 54 of these 63 participants completed 5 years of LTFU and were evaluated for relapse.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN + RBV: LTFU (All) | Number of Participants Who Relapsed At End of LTFU Year 5 | 0 participants |