Hepatitis C
Conditions
Brief summary
The objective of this study is to evaluate the efficacy of three regimens of pegylated interferon-alfa 2b (PEG-IFN) either as monotherapy or in combination with ribavirin in participants with acute hepatitis C. After 12 weeks of observation from disease onset, participants will receive one of the following regimens: (1) a 24-week course of PEG-IFN monotherapy (PEG-IFN 24); or (2) a 12-week course of PEG-IFN monotherapy (PEG-IFN-12); or (3) a 12-week course of PEG-IFN in combination with ribavirin (PEG-IFN + RVB 12). After the treatment period, participants will enter a 12-month follow-up.
Interventions
BIOLOGICALPegylated interferon alfa-2b
1.5 ug/kg/week SC for 12 or 24 weeks
DRUGRibavirin
Ribavirin at the dose of 10.6 mg/kg/day for 12 weeks
Sponsors
Bioikos Ambiente Srl
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with acute hepatitis C virus (HCV). * Normal and Elevated serum alanine transferase (ALT) levels * Positive serum HCV-RNA. * Aged between 18 and 65 years. * Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of the drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and additionally for participants treated with ribavirin, for 6 months (for woman) and 7 months (for man and his partner) after treatment completion
Exclusion criteria
* Liver disease unrelated to HCV infection * Hemoglobin (Hgb) \<12g/dL in women and \<13g/dL in men; white blood cells (WBC) \<3,000/uL; platelets (PLTs) \<100,000/ul * Women with ongoing pregnancy or who are breast feeding * History of severe psychiatric disease, especially depression * History of neurologic disease, especially epilepsy * History or evidence of symptoms of severe cardiac, gastrointestinal and kidney disease * Positive anti-Human Immunodeficiency Virus (HIV) antibodies * Positive anti-nuclear antibodies (ANA) and/or Anti-Smooth Muscle Antibody (ASMA) (\>1/80) * Positive Hepatitis B surface antigen (HBsAg) * History of having received any systemic anti-neoplastic or immunomodulatory treatment in the previous 6 months * History or other evidence of severe illness or any other conditions which would make the participants, in the opinion of investigator, unsuitable for the study (active drug addict except those under methadone treatment, thalassemic, dyalized included)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period | Evaluated at the end of 6 months | SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Response at the End of Treatment Follow-up (ETR) | At the end of treatment (either 12 weeks or 24 weeks depending on randomization). | 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. |
| Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). | At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization). | LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was \<15 IU/mL. |
| Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 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. | 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. |
| Number of Participants With Rapid Virologic Response (RVR) | Evaluated at 2 and 4 weeks of treatment | 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. |
| Number of Peripheral Blood Mononuclear Cells (PBMCs) | Treatment Weeks 2, 4, 8, and 12 | Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12. |
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| PEG-IFN 24 Pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks | 44 |
| PEG-IFN 12 Pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks | 43 |
| 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 | 43 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment | Adverse Event | 2 | 0 | 0 |
| Treatment | Poor Protocol Compliance | 1 | 0 | 0 |
| Treatment | Protocol Violation | 2 | 1 | 0 |
| Treatment | Serious Adverse Event | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | PEG-IFN 24 | PEG-IFN 12 | PEG-IFN + RVB 12 | Total |
|---|---|---|---|---|
| Age, Continuous | 36.55 years STANDARD_DEVIATION 13.86 | 38.32 years STANDARD_DEVIATION 13.95 | 38.52 years STANDARD_DEVIATION 12.48 | 37.79 years STANDARD_DEVIATION 13.37 |
| Region of Enrollment Italy | 44 participants | 43 participants | 43 participants | 130 participants |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 6 Participants | 37 Participants |
| Sex: Female, Male Male | 29 Participants | 27 Participants | 37 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 43 | 43 / 44 | 42 / 43 |
| serious Total, serious adverse events | 3 / 43 | 4 / 44 | 4 / 43 |
Outcome results
Primary
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.
Time frame: Evaluated at the end of 6 months
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN 24 | Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period | 23 participants |
| PEG-IFN 12 | Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period | 20 participants |
| PEG-IFN + RVB 12 | Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period | 21 participants |
Secondary
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN 24 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | End of Treatment | 28 participants |
| PEG-IFN 24 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 12-month Follow-up Period | 27 participants |
| PEG-IFN 24 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 6-month Follow-up Period | 31 participants |
| PEG-IFN 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | End of Treatment | 31 participants |
| PEG-IFN 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 6-month Follow-up Period | 27 participants |
| PEG-IFN 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 12-month Follow-up Period | 23 participants |
| PEG-IFN + RVB 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | End of Treatment | 32 participants |
| PEG-IFN + RVB 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 12-month Follow-up Period | 23 participants |
| PEG-IFN + RVB 12 | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 6-month Follow-up Period | 28 participants |
Secondary
Number of Participants With Rapid Virologic Response (RVR)
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.
Time frame: Evaluated at 2 and 4 weeks of treatment
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN 24 | Number of Participants With Rapid Virologic Response (RVR) | 2 weeks after start of treatment | 24 participants |
| PEG-IFN 24 | Number of Participants With Rapid Virologic Response (RVR) | 4 weeks after start of treatment | 28 participants |
| PEG-IFN 12 | Number of Participants With Rapid Virologic Response (RVR) | 2 weeks after start of treatment | 25 participants |
| PEG-IFN 12 | Number of Participants With Rapid Virologic Response (RVR) | 4 weeks after start of treatment | 35 participants |
| PEG-IFN + RVB 12 | Number of Participants With Rapid Virologic Response (RVR) | 2 weeks after start of treatment | 23 participants |
| PEG-IFN + RVB 12 | Number of Participants With Rapid Virologic Response (RVR) | 4 weeks after start of treatment | 34 participants |
Secondary
Number of Peripheral Blood Mononuclear Cells (PBMCs)
Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12.
Time frame: Treatment Weeks 2, 4, 8, and 12
Population: 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.
Secondary
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).
LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was \<15 IU/mL.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN 24 | Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). | 20 participants |
| PEG-IFN 12 | Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). | 19 participants |
| PEG-IFN + RVB 12 | Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). | 19 participants |
Secondary
Virologic Response at the End of Treatment Follow-up (ETR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN 24 | Virologic Response at the End of Treatment Follow-up (ETR) | 26 participants |
| PEG-IFN 12 | Virologic Response at the End of Treatment Follow-up (ETR) | 28 participants |
| PEG-IFN + RVB 12 | Virologic Response at the End of Treatment Follow-up (ETR) | 27 participants |