Hepatitis C, Chronic
Conditions
Brief summary
This is a single-arm, multicenter study of boceprevir (BOC) in combination with peginterferon plus ribavirin (PEG/RBV) in adult chronic hepatitis C (CHC) genotype 1 participants who completed their per-protocol defined treatment and did not achieve sustained viral response (SVR) while in the PEG/RBV control arm(s) of an Schering-Plough Research Institute (SPRI) study of BOC combination therapy. Participants who are able to enroll in this study within 2 weeks after the last dose of PEG/RBV in previous protocol are to receive BOC+ PEG/RBV for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who are not able to enroll in this study within 2 weeks after the last dose of PEG/RBV in previous protocol are to receive PEG/RBV for 4 weeks followed by BOC+ PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up.
Interventions
DRUGBoceprevir
Boceprevir, 200-mg capsules, 800 mg three times a day (TID) orally (PO)
BIOLOGICALPeginterferon alfa-2b (SCH 54031)
Peginterferon alfa-2b 1.5 µg/kg/week subcutaneously (SC)
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have been assigned to a PEG/RBV control arm in a previous SPRI study of BOC, must have completed treatment as per protocol, and have been compliant with all study treatment and scheduled procedures within the previous study. * Participant must have received at least 12 weeks of treatment with PEG/RBV and must have discontinued treatment in the previous study due to the futility rule (as defined in the previous protocol), had virologic breakthrough, or relapse. * Participant must have had detectable HCV-RNA upon completion of the previous study. * Participant and participant partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to starting any study treatment and to continue until at least 6 months after the last doses of study drugs, or longer if dictated by local regulations. * Participant must be willing to give written informed consent.
Exclusion criteria
* All participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24); | From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through Follow-Up Week (FW) 24 (up to 68 weeks) | SVR24 was defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week (FW) 24. SVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies. |
| Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through FW 24 (up to 68 weeks) | AE= any untoward medical occurrence in a participant administered a pharmaceutical product/biologic (at any dose), whether or not considered related to the use of that product. Included the onset of new illness and the exacerbation of pre-existing conditions. Clinically significant laboratory abnormalities that required intervention/additional therapy, required a dose modification, or were associated with a clinical manifestation were considered AEs. SAE= any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, or was a congenital anomaly or birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Early Virologic Response (EVR) | From TW 1 to TW 12 | EVR was defined as undetectable HCV-RNA at TW 12 of BOC + PEG/RBV. EVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies. |
Participant flow
Pre-assignment details
168 participants enrolled and received at least one dose of study medication. Participants were categorized by prior treatment response on the referring study: prior null response, prior partial response, prior relapse, or other.
Participants by arm
| Arm | Count |
|---|---|
| BOC + PEG/RBV: Prior Null Responders Participants who achieved null response (defined as \<2-log10 decrease and detectable HCV RNA at TW 12 of PEG/RBV) after completing treatment on the PEG/RBV control arm on a previous SPRI study received BOC + PEG/RBV on the current study for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who were not able to enroll on the current study within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. | 52 |
| BOC + PEG/RBV: Prior Partial Responders Participants who achieved partial response (defined as ≥2-log10 decrease in HCV-RNA by TW 12 and detectable HCV-RNA at end of PEG/RBV) after completing treatment on the PEG/RBV control arm on a previous SPRI study received BOC + PEG/RBV on the current study for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who were not able to enroll on the current study within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. | 85 |
| BOC + PEG/RBV: Prior Relapsers Participants who achieved prior relapse (defined as undetectable HCV-RNA at end of treatment, and detectable HCV-RNA during follow-up period) after completing treatment on the PEG/RBV control arm on a previous SPRI study received BOC + PEG/RBV on the current study for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who were not able to enroll on the current study within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. | 29 |
| BOC + PEG/RBV: Other Participants who were characterized as Other (not in the categories of prior treatment failure as defined by this protocol), after completing treatment on the PEG/RBV control arm on a previous SPRI study, received BOC + PEG/RBV on the current study for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who were not able to enroll on the current study within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. | 2 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up Phase | Administrative | 0 | 1 | 1 | 0 |
| Follow-Up Phase | Adverse Event | 0 | 0 | 1 | 0 |
| Follow-Up Phase | Lost to Follow-up | 3 | 1 | 2 | 0 |
| Follow-Up Phase | Reasons Unrelated To Assigned Treatment | 1 | 2 | 0 | 0 |
| Follow-Up Phase | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Follow-Up Phase | Withdrew Due To Retreatment Opportunity | 1 | 0 | 0 | 0 |
| Treatment Phase | Adverse Event | 2 | 6 | 6 | 0 |
| Treatment Phase | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Treatment Phase | Non-Compliance With Protocol | 0 | 1 | 1 | 0 |
| Treatment Phase | Reasons Unrelated To Assigned Treatment | 3 | 3 | 1 | 0 |
| Treatment Phase | Treatment Failure | 23 | 10 | 0 | 0 |
| Treatment Phase | Withdrawal by Subject | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | BOC + PEG/RBV: Prior Null Responders | BOC + PEG/RBV: Prior Partial Responders | BOC + PEG/RBV: Prior Relapsers | BOC + PEG/RBV: Other | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 7.7 | 52.6 years STANDARD_DEVIATION 8.4 | 53.6 years STANDARD_DEVIATION 6.4 | 52.0 years STANDARD_DEVIATION 1.4 | 52.3 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 19 Participants | 25 Participants | 10 Participants | 1 Participants | 55 Participants |
| Sex: Female, Male Male | 33 Participants | 60 Participants | 19 Participants | 1 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 161 / 168 |
| serious Total, serious adverse events | 18 / 168 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL
AE= any untoward medical occurrence in a participant administered a pharmaceutical product/biologic (at any dose), whether or not considered related to the use of that product. Included the onset of new illness and the exacerbation of pre-existing conditions. Clinically significant laboratory abnormalities that required intervention/additional therapy, required a dose modification, or were associated with a clinical manifestation were considered AEs. SAE= any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, or was a congenital anomaly or birth defect.
Time frame: From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through FW 24 (up to 68 weeks)
Population: All Treated Participants: All enrolled participants who received at least one dose of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | All Treatment-Related SAEs | 7 percentage of participants |
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | SAEs Related to BOC+PEG or BOC+P/R | 4 percentage of participants |
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | Neutrophil Count <0.75 × 10^9/L | 25 percentage of participants |
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | Hgb <10 g/dL | 53 percentage of participants |
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | AEs Leading to DC | 8 percentage of participants |
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | AEs Leading to DM | 35 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24);
SVR24 was defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week (FW) 24. SVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies.
Time frame: From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through Follow-Up Week (FW) 24 (up to 68 weeks)
Population: All BOC-Treated Participants: All enrolled participants who received at least 1 dose of BOC. Data for 2 Other participants were included in the calculations for BOC + PEG/RBV: All (n=164). 4 discontinued during the 4-week PEG/RBV lead-in and did not receive BOC and thus were excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24); | 41 percentage of participants |
| BOC + PEG/RBV: Prior Partial Responders | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24); | 67 percentage of participants |
| BOC + PEG/RBV: Prior Relapsers | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24); | 96 percentage of participants |
| BOC + PEG/RBV: All | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24); | 65 percentage of participants |
Secondary
Percentage of Participants With Early Virologic Response (EVR)
EVR was defined as undetectable HCV-RNA at TW 12 of BOC + PEG/RBV. EVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies.
Time frame: From TW 1 to TW 12
Population: All BOC-Treated Participants: All enrolled participants who received at least 1 dose of BOC. Data for 2 Other participants were included in the calculations for BOC + PEG/RBV: All (n=164). 4 discontinued during the 4-week PEG/RBV lead-in and did not receive BOC and thus were excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOC + PEG/RBV: Prior Null Responders | Percentage of Participants With Early Virologic Response (EVR) | 49 percentage of participants |
| BOC + PEG/RBV: Prior Partial Responders | Percentage of Participants With Early Virologic Response (EVR) | 76 percentage of participants |
| BOC + PEG/RBV: Prior Relapsers | Percentage of Participants With Early Virologic Response (EVR) | 100 percentage of participants |
| BOC + PEG/RBV: All | Percentage of Participants With Early Virologic Response (EVR) | 73 percentage of participants |