Hepatitis C, Chronic
Conditions
Brief summary
This single arm study will assess the efficacy and safety of PEGASYS in patients with chronic hepatitis C and end-stage renal disease, including patients on hemodialysis. Patients will receive PEGASYS at a dose of 180 micrograms weekly; those with a calculated glomerular filtration rate of \<15mL/min will receive a reduced dose of 135 micrograms weekly. Following 48 weeks of treatment there will be a 24 week period of treatment-free follow-up. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGpeginterferon alfa-2a [Pegasys]
180 micrograms or 135 micrograms sc weekly for 48 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-60 years of age; * chronic hepatitis C; * chronic renal failure, including patients on hemodialysis therapy; * detectable HCV RNA levels (\>500IU/mL).
Exclusion criteria
* concurrent active hepatitis A or B; * history or evidence of a medical condition associated with chronic liver disease other than HCV; * history or other evidence of decompensated liver disease; * therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment \<=6 months prior to study; * acute renal failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks Following Treatment Completion | At Week 72 | Sustained virologic response is defined as undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) levels (\<50 international units \[IU\]/mL) at 24 weeks following the completion of 48 weeks treatment period (Week 72). |
| Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid Level at Week 24 and Week 48 | At Week 24 and Week 48 | HCV RNA level less than 50 IU/mL was considered to be undetectable. |
| Percentage of Participants With At Least a 2log10 Drop in Hepatitis C Virus Ribonucleic Acid at Week 24 as Compared to Baseline | From Baseline (Days -30 to -1) and Week 24 | The table below shows the percentage of participants with at least 2log10 drop in HCV RNA level at Week 24 as compared to Baseline (Screening visit \[Days -30 to -1\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Blood Pressure up to Week 72 | From Baseline (Days -30 to -1) to Week 72 | Mean change from Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP) was recorded at Baseline (Screening visit \[Days -30 to -1\]) and at various Visits (V): Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7) and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10). |
| Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Up to Week 72 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect |
| Mean Change From Baseline in Heart Rate up to Week 72 | From Baseline (Days -30 to -1) to Week 72 | Mean change from baseline in heart rate was recorded at Baseline (Screening visit \[Days -30 to -1\]), and at various Visits (V): Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7), and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10). |
| Number of Participants Who Prematurely Withdrew From the Treatment Over a Period of 48 Weeks | Up to Week 48 | Participants who prematurely withdrew from the treatment for the following reasons: personal reasons (not related to the study), adverse events, and drug unavailability, are presented. |
| Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Up to Week 72 | Marked abnormal laboratory parameters included serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGTP), total bilirubin, alkaline phosphatase (ALP), ferritin and transferrin saturation. These laboratory parameters were evaluated at Baseline (Screening visit \[Days -30 to -1\]) and at various Visits (V): Week 0 (V1), Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7) and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10). |
Countries
Russia
Participant flow
Recruitment details
A total of 27 participants were enrolled in this study conducted from 2006 to 2011 at 5 centers in Russian Federation.
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alpha-2a Eligible participants were administered peginterferon alpha-2a (40 kDa), 180 mcg as a subcutaneous injection, once in a week, for 48 weeks. Participants with a calculated GFR of \<15 mL/min were administered a reduced dose of 135 mcg as a subcutaneous injection, once in a week, for 48 weeks. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Drug unavailability | 1 |
| Overall Study | Personal reasons | 5 |
Baseline characteristics
| Characteristic | Peginterferon Alpha-2a |
|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 27 |
| serious Total, serious adverse events | 2 / 27 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks Following Treatment Completion
Sustained virologic response is defined as undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) levels (\<50 international units \[IU\]/mL) at 24 weeks following the completion of 48 weeks treatment period (Week 72).
Time frame: At Week 72
Population: ITT population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a | Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks Following Treatment Completion | 55.6 Percentage of participants |
Primary
Percentage of Participants With At Least a 2log10 Drop in Hepatitis C Virus Ribonucleic Acid at Week 24 as Compared to Baseline
The table below shows the percentage of participants with at least 2log10 drop in HCV RNA level at Week 24 as compared to Baseline (Screening visit \[Days -30 to -1\]).
Time frame: From Baseline (Days -30 to -1) and Week 24
Population: ITT population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a | Percentage of Participants With At Least a 2log10 Drop in Hepatitis C Virus Ribonucleic Acid at Week 24 as Compared to Baseline | 33.3 Percentage of participants |
Primary
Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid Level at Week 24 and Week 48
HCV RNA level less than 50 IU/mL was considered to be undetectable.
Time frame: At Week 24 and Week 48
Population: ITT population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a | Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid Level at Week 24 and Week 48 | At Week 24 | 59.3 Percentage of participants |
| Peginterferon Alpha-2a | Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid Level at Week 24 and Week 48 | At Week 48 | 48.1 Percentage of participants |
Secondary
Mean Change From Baseline in Blood Pressure up to Week 72
Mean change from Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP) was recorded at Baseline (Screening visit \[Days -30 to -1\]) and at various Visits (V): Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7) and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10).
Time frame: From Baseline (Days -30 to -1) to Week 72
Population: ITT population included all enrolled participants who received at least one dose of study medication. Number of participants evaluable at a particular visit was determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V2, n=27 | -0.7 Millimeter (mm) of Mercury | Standard Deviation 8.6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V3, n=27 | 0.6 Millimeter (mm) of Mercury | Standard Deviation 12.1 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V4, n=26 | -2.9 Millimeter (mm) of Mercury | Standard Deviation 7.2 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V5, n=23 | -1.3 Millimeter (mm) of Mercury | Standard Deviation 10.1 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V6, n=23 | -2.6 Millimeter (mm) of Mercury | Standard Deviation 9 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V7, n=19 | -3.7 Millimeter (mm) of Mercury | Standard Deviation 9.6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V8, n=27 | -4.6 Millimeter (mm) of Mercury | Standard Deviation 8.1 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V9, n=21 | -3.6 Millimeter (mm) of Mercury | Standard Deviation 9.1 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | DBP, V10, n=21 | -3.8 Millimeter (mm) of Mercury | Standard Deviation 9.2 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V2, n=27 | -2.8 Millimeter (mm) of Mercury | Standard Deviation 12.9 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V3, n=27 | 1.3 Millimeter (mm) of Mercury | Standard Deviation 15.6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V4, n=26 | -4.0 Millimeter (mm) of Mercury | Standard Deviation 11.6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V5, n=23 | -0.7 Millimeter (mm) of Mercury | Standard Deviation 12 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V6, n=23 | -0.4 Millimeter (mm) of Mercury | Standard Deviation 10.3 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V7, n=19 | -4.2 Millimeter (mm) of Mercury | Standard Deviation 13.2 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V8, n=27 | -5.2 Millimeter (mm) of Mercury | Standard Deviation 11.3 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V9, n=21 | -3.1 Millimeter (mm) of Mercury | Standard Deviation 17.4 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Blood Pressure up to Week 72 | SBP, V10, n=21 | -4.5 Millimeter (mm) of Mercury | Standard Deviation 14.7 |
Secondary
Mean Change From Baseline in Heart Rate up to Week 72
Mean change from baseline in heart rate was recorded at Baseline (Screening visit \[Days -30 to -1\]), and at various Visits (V): Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7), and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10).
Time frame: From Baseline (Days -30 to -1) to Week 72
Population: ITT population included all enrolled participants who received at least one dose of study medication. Number of participants evaluable at a particular visit was determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V2, n=27 | 0.7 Beats per minute (bpm) | Standard Deviation 4.9 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V3, n=27 | 1.5 Beats per minute (bpm) | Standard Deviation 4.2 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V4, n=26 | 2.6 Beats per minute (bpm) | Standard Deviation 7.9 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V5, n=23 | 1.1 Beats per minute (bpm) | Standard Deviation 5.6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V6, n=23 | 0.5 Beats per minute (bpm) | Standard Deviation 6 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V7, n=19 | 1.3 Beats per minute (bpm) | Standard Deviation 6.4 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V8, n=27 | 2.0 Beats per minute (bpm) | Standard Deviation 5.2 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V9, n=21 | 1.4 Beats per minute (bpm) | Standard Deviation 3.1 |
| Peginterferon Alpha-2a | Mean Change From Baseline in Heart Rate up to Week 72 | V10, n=21 | -0.2 Beats per minute (bpm) | Standard Deviation 4.4 |
Secondary
Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect
Time frame: Up to Week 72
Population: Safety population included all enrolled participants who received at least one dose of study medication, whether withdrawn prematurely or not, and who had at least one follow-up data point were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Participants with any AEs | 10 Participants |
| Peginterferon Alpha-2a | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Participants with any SAEs | 2 Participants |
Secondary
Number of Participants Who Prematurely Withdrew From the Treatment Over a Period of 48 Weeks
Participants who prematurely withdrew from the treatment for the following reasons: personal reasons (not related to the study), adverse events, and drug unavailability, are presented.
Time frame: Up to Week 48
Population: ITT population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a | Number of Participants Who Prematurely Withdrew From the Treatment Over a Period of 48 Weeks | Personal reasons (not related to the study) | 5 Participants |
| Peginterferon Alpha-2a | Number of Participants Who Prematurely Withdrew From the Treatment Over a Period of 48 Weeks | Adverse events | 2 Participants |
| Peginterferon Alpha-2a | Number of Participants Who Prematurely Withdrew From the Treatment Over a Period of 48 Weeks | Drug unavailability | 1 Participants |
Secondary
Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks
Marked abnormal laboratory parameters included serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGTP), total bilirubin, alkaline phosphatase (ALP), ferritin and transferrin saturation. These laboratory parameters were evaluated at Baseline (Screening visit \[Days -30 to -1\]) and at various Visits (V): Week 0 (V1), Week 2 (V2), Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6) and Week 48 (V7) and after treatment completion at follow-up (FU) Week 4 (Week 52, V8), FU Week 12 (Week 60, V9), and FU Week 24 (Week 72, V10).
Time frame: Up to Week 72
Population: ITT population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, Baseline | 6 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V1 | 5 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V2 | 4 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V3 | 4 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V4 | 6 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V5 | 8 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V6 | 5 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V7 | 2 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V8 | 4 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V9 | 3 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGPT Increased, V10 | 3 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGOT Increased, Baseline | 4 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | SGOT Increased, V3 | 2 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | GGTP Increased, V3 | 1 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Total bilirubin Increased, Baseline | 1 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | ALP Increased Baseline | 7 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | ALP Increased, V3 | 9 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Increased, Baseline | 18 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Decreased, Baseline | 1 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Increased, V1 | 18 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Increased, V4 | 17 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Increased, V5 | 14 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Ferritin Increased, V7 | 14 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Increased, Baseline | 7 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Decreased, Baseline | 2 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Increased, V1 | 8 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Decreased, V1 | 1 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Increased, V4 | 7 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Increased, V5 | 4 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Decreased, V5 | 1 Participants |
| Peginterferon Alpha-2a | Number of Participants With Any Marked Abnormality in Laboratory Parameters Over a Period of 72 Weeks | Transferrin saturation Increased, V7 | 7 Participants |