Chronic Hepatitis C (HCV)
Conditions
Keywords
Hepatitis C, HCV, treatment-naive
Brief summary
This is a proof-of-concept study which will provide data about the safety and antiviral activity of several doses of the investigational drug IDX184 given for 3 days in treatment-naive HCV genotype 1-infected subjects so that optimal doses can be chosen for testing in later studies.
Interventions
DRUGIDX184
oral dose, active or placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18-65 years old 2. Subject of childbearing potential must agree to use a consistent form of an acceptable double-barrier method of birth control. 3. Plasma HCV RNA ≥ 5 log10 IU/mL 4. HCV genotype 1
Exclusion criteria
1. Received prior antiviral treatment for hepatitis C infection 2. Subject is pregnant or breastfeeding 3. Body Mass Index (BMI) \> 32 4. Currently abusing alcohol or illicit drugs 5. Currently receiving methadone, buprenorphine or other drugs for the treatment of opioid addiction 6. Co-infected with hepatitis B virus (HBV, HBsAg positive) and/or human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | 17 days | Monitoring of adverse events, physical examination, routine safety laboratory parameters and electrocardiograms. 1=mild, 2=moderate, 3=severe, 4=potentially life-threatening |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | Baseline to 4 days | Measures how much virus is in the blood. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 8 |
| IDX184 25 mg | 8 |
| IDX184 50 mg | 8 |
| IDX184 75 mg | 8 |
| IDX184 100 mg | 9 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Non-compliance | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | IDX184 25 mg | IDX184 50 mg | IDX184 75 mg | IDX184 100 mg |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 9 Participants |
| Age, Continuous | 48.1 years STANDARD_DEVIATION 6.94 | 49.3 years STANDARD_DEVIATION 7.63 | 48.3 years STANDARD_DEVIATION 6.5 | 48.8 years STANDARD_DEVIATION 5.85 | 47.3 years STANDARD_DEVIATION 8.12 | 47.2 years STANDARD_DEVIATION 7.89 |
| Region of Enrollment Argentina | 3 participants | 1 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Austria | 2 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 36 participants | 6 participants | 8 participants | 8 participants | 7 participants | 7 participants |
| Sex: Female, Male Female | 12 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 29 Participants | 5 Participants | 6 Participants | 7 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 2 / 8 | 3 / 8 | 3 / 8 | 5 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 9 |
Outcome results
Primary
Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events
Monitoring of adverse events, physical examination, routine safety laboratory parameters and electrocardiograms. 1=mild, 2=moderate, 3=severe, 4=potentially life-threatening
Time frame: 17 days
Population: Safety population consisted of all subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of sub. with any Grade 3/4 lab abnormality | 1 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Time, high | 0 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Pancreatic Amylase, high | 1 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Urine Erythrocytes, high | 0 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of subjects with any adverse event | 5 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Triacylglycerol Lipase, high | 0 participants |
| Placebo | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Intl. Normalized Ratio, high | 0 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Triacylglycerol Lipase, high | 1 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Intl. Normalized Ratio, high | 0 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Urine Erythrocytes, high | 0 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of subjects with any adverse event | 2 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of sub. with any Grade 3/4 lab abnormality | 1 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Time, high | 0 participants |
| IDX184 25 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Pancreatic Amylase, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Urine Erythrocytes, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Pancreatic Amylase, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of sub. with any Grade 3/4 lab abnormality | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Triacylglycerol Lipase, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Intl. Normalized Ratio, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Time, high | 0 participants |
| IDX184 50 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of subjects with any adverse event | 3 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of sub. with any Grade 3/4 lab abnormality | 0 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of subjects with any adverse event | 3 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Time, high | 0 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Urine Erythrocytes, high | 0 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Pancreatic Amylase, high | 0 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Intl. Normalized Ratio, high | 0 participants |
| IDX184 75 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Triacylglycerol Lipase, high | 0 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Pancreatic Amylase, high | 0 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of subjects with any adverse event | 5 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Number of sub. with any Grade 3/4 lab abnormality | 2 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Intl. Normalized Ratio, high | 1 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Prothrombin Time, high | 1 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Urine Erythrocytes, high | 1 participants |
| IDX184 100 mg | Number of Subjects With Any Adverse Event (Side Effect) and the Severity of Those Adverse Events | Grade 3/4 Triacylglycerol Lipase, high | 1 participants |
Secondary
Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid)
Measures how much virus is in the blood.
Time frame: Baseline to 4 days
Population: efficacy evaluable population = a) must have received all 3 doses of study drug b) must have baseline and at least one post-baseline HCV RNA determination
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | -0.1 log10 IU/mL | Standard Deviation 0.3 |
| IDX184 25 mg | Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | -0.5 log10 IU/mL | Standard Deviation 0.6 |
| IDX184 50 mg | Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | -0.7 log10 IU/mL | Standard Deviation 0.2 |
| IDX184 75 mg | Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | -0.6 log10 IU/mL | Standard Deviation 0.3 |
| IDX184 100 mg | Antiviral Activity at Day 4. Change in Plasma HCV RNA (Hepatitis C Virus Ribonucleic Acid) | -0.7 log10 IU/mL | Standard Deviation 0.5 |