Hepatitis C, Chronic
Conditions
Brief summary
This study evaluated the safety and efficacy of peginterferon alfa-2a monotherapy in participants with Chronic Hepatitis C (CHC) who have End-Stage Renal Disease (ESRD) and were undergoing hemodialysis.
Interventions
DRUGPeginterferon alfa-2a
Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a either 135 or 90 mcg SC once weekly up to Week 48.
Sponsors
Hoffmann-La Roche
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
* Serum hepatitis C virus ribonucleic acid (HCV RNA) quantifiable at greater than (\>) 600 IU/mL * Liver biopsy consistent with chronic hepatitis C infection obtained within 2 years of enrollment * Compensated liver disease without cirrhosis * Participants with end-stage renal disease undergoing hemodialysis * Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug * All fertile participants must have been using effective contraception during treatment with study drug
Exclusion criteria
* Interferon therapy at any previous time * Liver cirrhosis * Signs and symptoms of hepatocellular carcinoma * History or other evidence of decompensated liver disease * Any investigational drug less than or equal to 6 weeks prior to the first dose of study drug * History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) * Poorly controlled diabetes * Thyroid dysfunction not adequately controlled * Evidence of severe retinopathy or clinically relevant ophthalmological disorder * Severe hyperparathyroidism defined as intact Parathyroid Hormone (PTH) \> 800 picogram/milliliter (pg/mL) * Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment ≤ 6 months prior to the first dose of study drug * Acute renal failure * Women with ongoing pregnancy or breast feeding * Positive test at screening for anti-HAV IgM Ab (hepatitis A virus immunoglobulin M antibody), hepatitis B surface antigen (HBsAg), anti-HBc (hepatitis B core) IgM Ab, anti-HIV (human immunodeficiency virus) Ab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Treatment | 24 weeks after end of treatment (Week 72) | SVR was defined as the percentage of patients with undetectable HCV RNA. SVR rate was calculated as the number of participants with an undetectable HCV RNA divided by the number of participants of the respective participant population. The last single HCV RNA less than (\<) 50 international units per millilitre (IU/mL) measured \>=140 days after treatment end (i.e., \>= 20 weeks after treatment end) was used to determine SVR. Participants without measurements in this time window were considered to be nonresponders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Virological Response (Non-detectable Hepatitis C Virus-ribonucleic Acid [HCV RNA]) at End of Treatment (EOT) | EOT (Week 48) | Virological response at the end of study treatment was defined as the percentage of participants with undetectable HCV RNA. This response rate at end of treatment was calculated as the number of participants with undetectable HCV RNA divided by the number of participants of the respective participant population. |
| Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 | Weeks 12 and 24 | Virological response at Weeks 12 and 24 was computed as the percentage of participants with at least a 2-log 10 decrease in HCV RNA at Weeks 12 and 24 as compared with baseline or with an unquantifiable (\< 600 IU/mL) or an undetectable HCV RNA test result (\< 50 IU/mL) at Week 12 and at Week 24, calculated as the number of participants meeting this criterion divided by the number of participants of the respective participant population. |
Countries
Austria, Brazil, France, Greece, Indonesia, Italy, Turkey (Türkiye), United Arab Emirates
Participant flow
Pre-assignment details
A total of 85 participants were randomly assigned to the two treatment groups (Peginterferon alfa-2a 135 mcg/week and Peginterferon alfa-2a 90 mcg/week). A total of 4 randomized participants did not receive any study drug.
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alfa-2a 135 Microgram (mcg) Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48. | 38 |
| Peginterferon Alfa-2a 90 mcg Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48. | 43 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event/intercurrent illness | 1 | 3 |
| Overall Study | Death | 4 | 0 |
| Overall Study | Did not cooperate/refused treatment | 3 | 3 |
| Overall Study | Failure to return | 0 | 1 |
| Overall Study | Insufficient therapeutic response | 2 | 4 |
Baseline characteristics
| Characteristic | Peginterferon Alfa-2a 135 Microgram (mcg) | Peginterferon Alfa-2a 90 mcg | Total |
|---|---|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 11.26 | 42.9 years STANDARD_DEVIATION 11.26 | 43.5 years STANDARD_DEVIATION 11.21 |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 23 Participants | 34 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 38 | 38 / 43 |
| serious Total, serious adverse events | 14 / 38 | 14 / 43 |
Outcome results
Primary
Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Treatment
SVR was defined as the percentage of patients with undetectable HCV RNA. SVR rate was calculated as the number of participants with an undetectable HCV RNA divided by the number of participants of the respective participant population. The last single HCV RNA less than (\<) 50 international units per millilitre (IU/mL) measured \>=140 days after treatment end (i.e., \>= 20 weeks after treatment end) was used to determine SVR. Participants without measurements in this time window were considered to be nonresponders.
Time frame: 24 weeks after end of treatment (Week 72)
Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alfa-2a 135 Microgram (mcg) | Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Treatment | 39.5 percentage of participants |
| Peginterferon Alfa-2a 90 mcg | Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Treatment | 34.9 percentage of participants |
Comparison: The odds ratio is the ratio of the odds of a response in the Peginterferon alfa-2a 135 mcg group with the odds of a response in the Peginterferon alfa-2a 90 mcg group.p-value: 0.674695% CI: [0.49, 3.06]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24
Virological response at Weeks 12 and 24 was computed as the percentage of participants with at least a 2-log 10 decrease in HCV RNA at Weeks 12 and 24 as compared with baseline or with an unquantifiable (\< 600 IU/mL) or an undetectable HCV RNA test result (\< 50 IU/mL) at Week 12 and at Week 24, calculated as the number of participants meeting this criterion divided by the number of participants of the respective participant population.
Time frame: Weeks 12 and 24
Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alfa-2a 135 Microgram (mcg) | Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 | Week 12 | 71.1 percentage of participants |
| Peginterferon Alfa-2a 135 Microgram (mcg) | Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 | Week 24 | 65.8 percentage of participants |
| Peginterferon Alfa-2a 90 mcg | Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 | Week 12 | 69.8 percentage of participants |
| Peginterferon Alfa-2a 90 mcg | Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 | Week 24 | 72.1 percentage of participants |
Comparison: Week 12: The odds ratio is the ratio of the odds of a response in the Peginterferon alfa-2a 135 mcg group with the odds of a response in the Peginterferon alfa-2a 90 mcg group.p-value: 0.884395% CI: [0.43, 2.68]Cochran-Mantel-Haenszel
Comparison: Week 24: The odds ratio is the ratio of the odds of a response in the Peginterferon alfa-2a 135 mcg group with the odds of a response in the Peginterferon alfa-2a 90 mcg group.p-value: 0.586695% CI: [0.28, 2.04]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Virological Response (Non-detectable Hepatitis C Virus-ribonucleic Acid [HCV RNA]) at End of Treatment (EOT)
Virological response at the end of study treatment was defined as the percentage of participants with undetectable HCV RNA. This response rate at end of treatment was calculated as the number of participants with undetectable HCV RNA divided by the number of participants of the respective participant population.
Time frame: EOT (Week 48)
Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alfa-2a 135 Microgram (mcg) | Percentage of Participants With Virological Response (Non-detectable Hepatitis C Virus-ribonucleic Acid [HCV RNA]) at End of Treatment (EOT) | 57.9 percentage of participants |
| Peginterferon Alfa-2a 90 mcg | Percentage of Participants With Virological Response (Non-detectable Hepatitis C Virus-ribonucleic Acid [HCV RNA]) at End of Treatment (EOT) | 48.8 percentage of participants |
Comparison: The odds ratio is the ratio of the odds of a response in the Peginterferon alfa-2a 135 mcg group with the odds of a response in the Peginterferon alfa-2a 90 mcg group.p-value: 0.392395% CI: [0.6, 3.76]Cochran-Mantel-Haenszel