Hepatitis C
Conditions
Keywords
PegInterferon alpha-2a, Ribavirin, Hepatitis C Virus, Sustained Virological Response, End of Treatment Response, Unipeg, Ribazole
Brief summary
Hepatitis C is a global problem, prevalent in developed as well as in the developing countries. New treatment regimens using PegInterferon in combination with ribavirin has led to improved sustained viral response rates for some genotypes. A single arm, open labeled, multicentre trial was conducted to evaluate the response rate and safety of PegInterferon alfa-2a (Unipeg®) plus ribavirin (Ribazole®) for the treatment of patients with chronic hepatitis C infection. RVR at 4 weeks, ETR at 24 weeks for genotype 3 and at 48 weeks for genotype 1 patients and SVR was determined at 24 weeks after completion of treatment. Quality of life at baseline and at follow-up visits were determined using SF-36.
Detailed description
A multicenter, phase IV, open labeled, single arm study was conducted. Total 110 patients were screened for recruitment. Out of which 67 subjects met the inclusion criteria, 3 failed to give the informed consent and were excluded. The final sample size of the study was 64 patients. The duration of study was August 2010 to September 2013. Peginterferon alfa-2a 180µg 20kDa (Unipeg®) solution for injection was administered as single dose sub-cutaneous once weekly for 24 weeks to patients with genotype 3 and 48 weeks in patients with genotype 1 at the site of recruitment. Ribavirin (Ribazole) orally were given in divided daily dose according to body weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Quality of life related Physical Component Score (PCS) & Mental Component Score (MCS) were measured through Health-Related Quality of Life (HRQOL) Questionnaire (SF-36). The SF-36 questionnaire was completed for all patients during their evaluations before treatment, at 4 weeks, at the end of treatment and at 24 weeks after completion of treatment.
Interventions
DRUGPeginterferon alfa-2a
PegInterferon alfa-2a 180mcg 20kDa administered subcutaneously once weekly for 24 weeks in genotype 3 and for 48 weeks in genotype 1 patients.
DRUGRibavirin
Ribavirin administered orally in a divided daily dose according to body weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
Sponsors
Dimension Research
Getz Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Written Informed consent 2. Treatment naïve patients 3. Serological evidence of hepatitis C infection by an anti-HCV antibody test 4. HCV positive by PCR 5. Genotype 1,2 and 3 6. BMI 20-28 7. Participants were the resident of city where he /she enrolled at their respective centre 8. No evidence of liver cirrhosis 9. No other significant hepatic or systemic disease 10. No evidence of hepatic encephalopathy 11. Normal thyroid functions (By testing TSH) 12. Adequate bone marrow, liver and renal functions test * Hematology: ANC≥1,000/mm3, Platelet count ≥100,000 mm3, Hemoglobin≥11.0g/dl in female and ≥ 12.0 g/dl in male * Blood Chemistry: Total Bilirubin≤2.0mg/dl, AST and ALT \<3 times normal * Creatinine Clearance \>50 ml/min * Proteinuria: ≤ 0.5 g per 24h. * Prothrombin Time or partial-thromboplastin time if ≤1.5 times the upper limit of the normal range.
Exclusion criteria
1. Unable to give consent 2. Prior treatment for Hepatitis C 3. Co-infection with HBV and HCV 4. Obesity 5. Iron overload 6. Other Genotypes e.g. 4, 5, 6 with their sub-types 7. Pregnant and lactating women 8. History of medical condition associated with chronic liver disease other than CHC (e.g. hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposure) 9. Uncontrolled Hypertension 10. Uncontrolled Diabetes 11. Severe Depression 12. Clinically significant cardio-vascular disease 13. Symptomatic peripheral vascular disease 14. Oral or parenteral anticoagulants or anti platelet agents 15. History of systemic anti-viral therapy at least three months prior to first dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Virological Response (SVR) | Post treatment Week 24 | To determine the SVR at 24 weeks after completion of treatment, among those who achieved ETR |
| Number of Participants With End Treatment Response | Upto 48 weeks | To determine the End Treatment Response (ETR) rate of all patients treated with PegInterferon alfa-2a plus Ribavirin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reported Adverse Events | Upto 48 weeks | To determine the number of patients treated with PegInterferon Alfa-2a plus Ribavirin who experience any adverse drug reaction. All ADR are reported as per patient information leaflet |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Rapid Virological Response (RVR) | 4 weeks | To evaluate the Rapid Virological Response (RVR) of all patients treated with PegInterferon Alfa-2a plus Ribavirin at 4 weeks of treatment |
| Mean of Physical Component Score & Mental Component Score to Determine Quality of Life | Upto 48 weeks | To determine and compare the changes in quality of life (QOL) from baseline to end of the treatment. Health-Related Quality of Life (HRQOL) Questionnaire (SF-36) was used to measure the quality of life. The SF-36 is a widely used questionnaire, and consists of 36 questions measuring eight concepts: Physical Function (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Role Emotional (RE), and Mental Health (MH). The scoring of the SF-36 questionnaire in our study was conducted upon a 0-100 scale, with higher scores reflecting better health status. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PegInterferon Alfa-2a and Ribavirin PegInterferon alfa-2a subcutaneously once weekly Ribavirin administered orally according to the body weight
Peginterferon alfa-2a: PegInterferon alfa-2a 180mcg 20kDa administered subcutaneously once weekly for 24 weeks in genotype 3 and for 48 weeks in genotype 1 patients.
Ribavirin: Ribavirin administered orally in a divided daily dose according to body weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) | 64 |
| Total | 64 |
Baseline characteristics
| Characteristic | PegInterferon Alfa-2a and Ribavirin |
|---|---|
| Age, Customized Count | 35.4 participants STANDARD_DEVIATION 9.5 |
| Number of HCV Patients confirmed through Polymerase Chain Reaction | 64 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 64 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Pakistan | 64 Participants |
| Sex: Female, Male Count Female | 28 Participants |
| Sex: Female, Male Count Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 64 |
| other Total, other adverse events | 10 / 64 |
| serious Total, serious adverse events | 0 / 64 |
Outcome results
Primary
Number of Participants With End Treatment Response
To determine the End Treatment Response (ETR) rate of all patients treated with PegInterferon alfa-2a plus Ribavirin
Time frame: Upto 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegInterferon Alfa-2a and Ribavirin | Number of Participants With End Treatment Response | 56 Participants |
Primary
Number of Participants With Sustained Virological Response (SVR)
To determine the SVR at 24 weeks after completion of treatment, among those who achieved ETR
Time frame: Post treatment Week 24
Population: Among those who achieved ETR (i.e. 56 participants) were eligible for SVR analysis after 24 weeks of post treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegInterferon Alfa-2a and Ribavirin | Number of Participants With Sustained Virological Response (SVR) | 49 Participants |
Secondary
Number of Participants Who Reported Adverse Events
To determine the number of patients treated with PegInterferon Alfa-2a plus Ribavirin who experience any adverse drug reaction. All ADR are reported as per patient information leaflet
Time frame: Upto 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegInterferon Alfa-2a and Ribavirin | Number of Participants Who Reported Adverse Events | 10 Participants |
Other Pre-specified
Mean of Physical Component Score & Mental Component Score to Determine Quality of Life
To determine and compare the changes in quality of life (QOL) from baseline to end of the treatment. Health-Related Quality of Life (HRQOL) Questionnaire (SF-36) was used to measure the quality of life. The SF-36 is a widely used questionnaire, and consists of 36 questions measuring eight concepts: Physical Function (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Role Emotional (RE), and Mental Health (MH). The scoring of the SF-36 questionnaire in our study was conducted upon a 0-100 scale, with higher scores reflecting better health status.
Time frame: Upto 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PegInterferon Alfa-2a and Ribavirin | Mean of Physical Component Score & Mental Component Score to Determine Quality of Life | Physical Component Score | 50.62 score on a scale | Standard Deviation 8.22 |
| PegInterferon Alfa-2a and Ribavirin | Mean of Physical Component Score & Mental Component Score to Determine Quality of Life | Mental Component Score | 54.89 score on a scale | Standard Deviation 9.61 |
Other Pre-specified
Number of Participants With Rapid Virological Response (RVR)
To evaluate the Rapid Virological Response (RVR) of all patients treated with PegInterferon Alfa-2a plus Ribavirin at 4 weeks of treatment
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegInterferon Alfa-2a and Ribavirin | Number of Participants With Rapid Virological Response (RVR) | 48 Participants |