Hepatitis C, Chronic
Conditions
Keywords
Prevention of Relapse, HCV genotype 1b, Recurrence
Brief summary
The purpose of this study is to determine whether lozenges of interferon-alpha that are dissolved in the mouth can prevent relapse in patients with hepatitis C virus infection who had a complete virologic response after receiving a combination of injected interferon-alpha and oral ribavirin.
Interventions
500 IU lozenges of natural human interferon-alpha for oral dissolution given once or three times per day for 24 weeks
DRUGplacebo lozenges
200 mg matching placebo lozenges
Sponsors
CytoPharm, Inc.
Ainos, Inc. (f/k/a Amarillo Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HCV genotype 1b * Will be completing pegylated IFN-alpha and ribavirin therapy within 4 weeks * Serum HCV RNA negative within 4 weeks of study entry
Exclusion criteria
* Child-Pugh score of B or C * Decompensated liver function * History of malignancy within past 5 years * Other causes of liver disease besides HCV infection * Uncontrolled diabetes or hypertension * Unwilling to use two forms of birth control during study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Rate | 48 weeks | Percentage of participants with a positive seum HCV RNA level at any post-baseline evaluation Serum HCV RNA was tested using a commercially available real-time polymerase-chain-reaction (PCR) assay kit (Roche Cobas TaqMan HCV assay kit) with a limit of detection of 15 IU/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normalization of ALT | 48 weeks | Percentage of participants with a normal serum ALT level at the end of the study |
| Change in Serum HCV RNA Concentration | 48 weeks | Change in serum HCV RNA concentration (log10 IU) from baseline to week 48 |
| Sustained Virologic Response Rate | 48 weeks | Percentage of participants who remained HCV RNA negative throughout the study |
| Change in Social Functioning | 48 weeks | Change in the Social Functioning domain of the SF-36 quality-of-life questionnaire from baseline to week 48 Social Functioning (SF) scores range from 0-100, with lower scores indicating that health/emotional problems have had a greater negative impact on social activities, compared to higher scores. SF scores are calculated using a proprietary algorithm based on responses to questions #6 and #10 on the SF-36, which are 5-point likert scales about the extent to which, and the amount of time with which physical or emotional problems have interfered with social activities. |
| Change in Fibrotest Score | 48 weeks | Change in fibrotest score from baseline to week 48 |
| Change in Serum ALT | 48 weeks | Change in Serum ALT concentration from baseline to week 48 |
Countries
Taiwan
Participant flow
Recruitment details
Subjects undergoing treatment for HCV infection at one of the 9 participating hospitals were approached, and those willing to sign informed consent were screened for eligibility.
Pre-assignment details
A total of 196 subjects were screened. All 169 subjects meeting eligibility criteria were randomized to one of the 3 treatment groups and all 169 were included in the intent-to-treat analysis.
Participants by arm
| Arm | Count |
|---|---|
| 500 IU qd 500 IU Interferon-alpha lozenge taken once per day plus 2 placebo lozenges | 59 |
| 500 IU Tid 500 IU interferon-alpha lozenge taken 3 times per day | 53 |
| Placebo placebo lozenges taken 3 times per day | 57 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 3 | 1 |
| Overall Study | Various | 4 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 8 | 6 | 4 |
Baseline characteristics
| Characteristic | 500 IU Tid | Placebo | 500 IU qd | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 10 Participants | 12 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 47 Participants | 47 Participants | 138 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 10.8 | 56.8 years STANDARD_DEVIATION 9.5 | 54.9 years STANDARD_DEVIATION 11.9 | 55.8 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment Taiwan | 53 participants | 57 participants | 59 participants | 169 participants |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 27 Participants | 78 Participants |
| Sex: Female, Male Male | 27 Participants | 32 Participants | 32 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 59 | 46 / 53 | 41 / 57 |
| serious Total, serious adverse events | 2 / 59 | 6 / 53 | 6 / 57 |
Outcome results
Primary
Relapse Rate
Percentage of participants with a positive seum HCV RNA level at any post-baseline evaluation Serum HCV RNA was tested using a commercially available real-time polymerase-chain-reaction (PCR) assay kit (Roche Cobas TaqMan HCV assay kit) with a limit of detection of 15 IU/ml.
Time frame: 48 weeks
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 IU qd | Relapse Rate | 30.5 percentage of participants |
| 500 IU Tid | Relapse Rate | 37.7 percentage of participants |
| Placebo | Relapse Rate | 35.1 percentage of participants |
p-value: 0.72Chi-squared
Secondary
Change in Fibrotest Score
Change in fibrotest score from baseline to week 48
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 IU qd | Change in Fibrotest Score | -0.37 units on a scale | Standard Deviation 0.48 |
| 500 IU Tid | Change in Fibrotest Score | -0.19 units on a scale | Standard Deviation 0.46 |
| Placebo | Change in Fibrotest Score | -0.31 units on a scale | Standard Deviation 0.37 |
Comparison: Fibrotest provides an estimate of liver fibrosis based on the values of 5 serum markers. Scores range from 0 to 1 with higher scores indicating a greater level of liver fibrosis. A negative change in Fibrotest score is therefore deemed to indicate improvement (reduction in fibrosis), while a positive change indicates worsening condition.p-value: 0.21Kruskal-Wallis
Secondary
Change in Serum ALT
Change in Serum ALT concentration from baseline to week 48
Time frame: 48 weeks
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 IU qd | Change in Serum ALT | 7.8 U/L | Standard Deviation 75.5 |
| 500 IU Tid | Change in Serum ALT | 0.6 U/L | Standard Deviation 36.6 |
| Placebo | Change in Serum ALT | 8.6 U/L | Standard Deviation 52.6 |
p-value: 0.3Kruskal-Wallis
Secondary
Change in Serum HCV RNA Concentration
Change in serum HCV RNA concentration (log10 IU) from baseline to week 48
Time frame: 48 weeks
Population: Intent-to-treat population
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| 500 IU qd | Change in Serum HCV RNA Concentration | 1.6 log10 IU | Standard Deviation 2.4 |
| 500 IU Tid | Change in Serum HCV RNA Concentration | 1.9 log10 IU | Standard Deviation 2.5 |
| Placebo | Change in Serum HCV RNA Concentration | 1.7 log10 IU | Standard Deviation 2.5 |
p-value: 0.77Kruskal-Wallis
Secondary
Change in Social Functioning
Change in the Social Functioning domain of the SF-36 quality-of-life questionnaire from baseline to week 48 Social Functioning (SF) scores range from 0-100, with lower scores indicating that health/emotional problems have had a greater negative impact on social activities, compared to higher scores. SF scores are calculated using a proprietary algorithm based on responses to questions #6 and #10 on the SF-36, which are 5-point likert scales about the extent to which, and the amount of time with which physical or emotional problems have interfered with social activities.
Time frame: 48 weeks
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 IU qd | Change in Social Functioning | 21.6 change in score | Standard Deviation 17.7 |
| 500 IU Tid | Change in Social Functioning | 16.3 change in score | Standard Deviation 20.9 |
| Placebo | Change in Social Functioning | 8.8 change in score | Standard Deviation 20.5 |
p-value: 0.0023Kruskal-Wallis
Secondary
Normalization of ALT
Percentage of participants with a normal serum ALT level at the end of the study
Time frame: 48 weeks
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 IU qd | Normalization of ALT | 71.2 percentage of participants |
| 500 IU Tid | Normalization of ALT | 60.4 percentage of participants |
| Placebo | Normalization of ALT | 64.9 percentage of participants |
p-value: 0.48Chi-squared
Secondary
Sustained Virologic Response Rate
Percentage of participants who remained HCV RNA negative throughout the study
Time frame: 48 weeks
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 IU qd | Sustained Virologic Response Rate | 71.2 percentage of participants |
| 500 IU Tid | Sustained Virologic Response Rate | 62.3 percentage of participants |
| Placebo | Sustained Virologic Response Rate | 66.7 percentage of participants |
p-value: 0.61Chi-squared
Post Hoc
Normalization of Platelets
Percentage of participants with a low platelet count at baseline who had a normal platelet count at the end of the study
Time frame: 48 weeks
Population: Participants with a baseline platelet count below 150 who were evaluable for response at week 48 were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 IU qd | Normalization of Platelets | 81.0 percentage of participants |
| 500 IU Tid | Normalization of Platelets | 50.0 percentage of participants |
| Placebo | Normalization of Platelets | 41.9 percentage of participants |
p-value: 0.03Chi-squared
p-value: 0.005Chi-squared