Hepatitis C, Chronic, Hepatitis C Virus
Conditions
Brief summary
Naïve patients with chronic hepatitis C (CHC) of any genotype will be treated with a standard treatment regimen (pegylated interferon and ribavirin) according to routine clinical practice in Russia. The objective of this study is to examine the influence of insulin resistance on the safety and efficacy of treatment with pegylated interferon and ribavirin and to determine the prevalence of insulin resistance in different populations of CHC patients.
Detailed description
consecutive patient sampling
Interventions
BIOLOGICALPegylated Interferon
Routine treatment with a combination of any pegylated interferon and ribavirin was used according to the label/local practice in Russia. The treatment course duration complied with the labeled dosage regimen. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. Therapy duration varied from 24 to 48 weeks depending on Hepatitis C virus (HCV) genotype, viral load, activity and stage of hepatitis C. The Sponsor did not provide formal drug supply.
DRUGRibavirin
Routine treatment with a combination of any pegylated interferon and ribavirin was used according to the label/local practice in Russia. The treatment course duration complied with the labeled dosage regimen. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C. The Sponsor did not provide formal drug supply.
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CHC according to local regulations * Naïve Pegylated Interferon (PEG-IFN) CHC patient * No contraindications for PEG-IFN CHC therapy * Negative urine pregnancy test result (for females of childbearing potential) documented within the 24-hour period prior to the first dose of study drugs. Additionally, all female patients of childbearing potential and all males with female partners of childbearing potential must use two forms of effective contraception (combined) during treatment and 6 months after treatment end * Willingness to give written informed consent and willingness to participate in and comply with the study requirements.
Exclusion criteria
* PEG-IFN treatment in history * Contraindications for PEG-IFN CHC therapy * Females who are pregnant or breast-feeding * Male partners of females who are pregnant * Potentially unreliable participants, and those judged by the investigator to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study | 24 weeks following completion of 24 or 48 weeks of therapy | Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as Homeostasis model assessment - of insulin-resistance \[HOMA-IR\] \>3) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively. |
| Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Week 24 or 48 after treatment start | Response following treatment (RFT) was assessed at the end of treatment (Visit 3) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the presence or absence of RFT. RFT was defined as undetectable plasma HCV-RNA at end of treatment. Visit 3 was considered Week 24 or Week 48 after treatment start depending on treatment duration. |
| Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | Virological relapse (VR) was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the percentage of participants who demonstrated VR. VR was defined as undetectable plasma HCV-RNA (RFT +) at end of treatment (Visit 3- considered Week 24 or Week 48 after treatment start depending on treatment duration), but lost RFT (considered sustained non-Responders) at end of study (Visit 4- considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively). |
| Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Week 12 after treatment start | Early Virological response (EVR) was assessed at 12 weeks after treatment start (Visit 2) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the percentage of participants who achieved EVR. EVR was defined as a substantial (greater than 2 log10) decrease in viral load (measured as International Units/milliliter) and/or negative Polymerase chain reaction (PCR)-based viral load qualitative result as assessed at visit 2 of the study. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon and Ribavirin Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous
injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the
morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C. | 250 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Pegylated Interferon and Ribavirin |
|---|---|
| Age, Continuous | 36.0 years STANDARD_DEVIATION 9.78 |
| Sex: Female, Male Female | 104 Participants |
| Sex: Female, Male Male | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 177 / 250 |
| serious Total, serious adverse events | 2 / 250 |
Outcome results
Primary
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study
Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Completer set for the primary analysis included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study | 81.2 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline
Early Virological response (EVR) was assessed at 12 weeks after treatment start (Visit 2) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the percentage of participants who achieved EVR. EVR was defined as a substantial (greater than 2 log10) decrease in viral load (measured as International Units/milliliter) and/or negative Polymerase chain reaction (PCR)-based viral load qualitative result as assessed at visit 2 of the study.
Time frame: Week 12 after treatment start
Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 210 participants demonstrated early virological response (N=158 and N=50). 2 participants of the 210 had missing values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 34.8 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 12.7 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 1.3 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 51.3 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 6.0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 40.0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 54.0 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline
Response following treatment (RFT) was assessed at the end of treatment (Visit 3) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the presence or absence of RFT. RFT was defined as undetectable plasma HCV-RNA at end of treatment. Visit 3 was considered Week 24 or Week 48 after treatment start depending on treatment duration.
Time frame: Week 24 or 48 after treatment start
Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 208 achieved RFT (N=156 and N=51) and were therefore included in this analysis. 1 participant of the 208 had missing values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 50.6 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 12.2 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 35.9 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 1.3 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 52.9 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 41.2 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 5.9 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline
SVR was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as Homeostasis model assessment - of insulin-resistance \[HOMA-IR\] \>3) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 181 achieved SVR (N=140 and N=40) and were therefore included in this analysis. 1 participant of the 181 had missing values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 45.7 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 38.6 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 14.3 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 1.4 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 7.5 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 47.5 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 45.0 Percentage of Participants |
Secondary
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline
Virological relapse (VR) was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR \>3) to investigate the percentage of participants who demonstrated VR. VR was defined as undetectable plasma HCV-RNA (RFT +) at end of treatment (Visit 3- considered Week 24 or Week 48 after treatment start depending on treatment duration), but lost RFT (considered sustained non-Responders) at end of study (Visit 4- considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 29 participants demonstrated virological relapse (N=18 and N=11) and were therefore included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 0 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 0 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 16.7 Percentage of Participants |
| Pegylated Interferon and Ribavirin | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 83.3 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Other | 0 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype III | 27.3 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype I | 72.7 Percentage of Participants |
| HOMA-IR >3 | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline | Genotype II | 0 Percentage of Participants |