Hepatitis C
Conditions
Brief summary
A Study to assess the general safety and tolerability of the administration of a 3-dose prime/boost regimen of the MRKAd5 HIV-1 gag vaccine (V520) in subjects with chronic hepatitis C virus infection.
Interventions
BIOLOGICALMRKAd5 HIV-1 gag vaccine (V520)
3-dose prime boosting regimen of 1.0-mL intramuscular injections of 1x10\^9 viral particles/dose of MRKAd5 HIV-1 gag vaccine (V520) at Day 1 and Weeks 4 and 26
BIOLOGICALComparator: Placebo
1.0 mL intramuscular injection of Placebo at Day 1 and Weeks 4 and 26
BIOLOGICALComparator: Open Label Tetanus and Diptheria Toxoids Adsorbed
0.5 mL Open Label Tetanus and Diptheria Toxoids Adsorbed (Td) intramuscular injection at Day 1 only
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 55 Years
Healthy volunteers
No
Inclusion criteria
* Subject who is of reproductive potential agrees to use a acceptable method of birth control through week 52 of the study
Exclusion criteria
* Subject weighs less than 110 lbs. * Subject has received treatment for hepatitis C virus infection in the 3 months before enrollment in this study or is anticipated to begin treatment with in 1 year after enrollment * Subject has any history of anaphylaxis or allergy to vaccine components * Subject has any history of anaphylaxis or allergy to Tetanus and Diphtheria Toxoids Adsorbed (Td) * Subject has clinical signs suggestive of cirrhosis * Subject has had a liver biopsy showing bridging fibrosis or cirrhosis * Subject is HBsAg positive * Subject has other known chronic liver disease * Subject has evidence of hepatocellular carcinoma on liver biopsy * Subject has had a liver transplant or is anticipated to have a liver transplant within 1 year of enrollment * Subject has been vaccinated with a live virus vaccine in the past 30 days * Subject has been vaccinated with an inactive virus vaccine in the past 14 days * Female subject is pregnant or breast-feeding, Male subject is planning to impregnate * Subject has active drug or alcohol abuse * Subject is at high risk for HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | up to Week 78 (52 weeks after boost injection) for systemic AEs, 29 days after any dose for laboratory AEs, and 5 days after any dose for injection-site AEs | Serious and non serious clinical (systemic and injection-site AEs), and laboratory AEs were collected. Systemic and laboratory AEs reflect any unfavorable & unintended change in the structure, function, or chemistry of the body. Injection-site AEs include any swelling, redness, pain or tenderness at the injection site. Vaccine-related AEs are those determined by the investigator to be possibly, probably, or definitely related to the administration of the vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Systemic and Laboratory Adverse Events (AE) | up to Week 260 (234 weeks after boost injection) for systemic AEs, 29 days after any dose for laboratory AEs, and 5 days after any dose for injection-site AEs | Adverse experiences collected include serious and non serious systemic AEs, injection-site AEs, and laboratory AEs. Systemic and laboratory AEs include any unfavorable & unintended change in the structure, function, or chemistry of the body. Injection-site AEs include any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to 5 days after any vaccine dose. |
| Immune Response by Levels of Unfractionated Gag-specific IFN-gamma Following a 3-dose Vaccine Regimen | Week 30 (4 weeks after boost injection) | Participants expressing HIV antigens (gag) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag-specific IFN-gamma were to be measured using an Enzyme Linked Immunospot Assay (ELISPOT), which measures spot forming cells per 10\^6 peripheral blood mononuclear cells (SFC per million PBMCs). No immunogenicity analyses were performed because the results from a previous study, V520-023 (NCT00095576), which used the same vaccine as the one used in this study (NCT00857311) proved it was not efficacious. |
Participant flow
Recruitment details
All participants had to be at low risk of acquiring human immunodeficiency virus (HIV) infection, and had to meet a number of laboratory criteria. They could not have received treatment for hepatitis C virus infection in the 3 months prior to enrollment and must not anticipate to begin treatment with in 1 year after enrollment.
Participants by arm
| Arm | Count |
|---|---|
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose Participants administered MRKAd5 HIV-1 gag vaccine 1x10\^9 viral particles (vp)/dose (V520), on Day 1, Week 4, and Week 26. | 9 |
| MRKAd5 HIV-1 Gag Vaccine 1x10^10 vp/Dose Participants were to be administered MRKAd5 HIV-1 gag 1x10\^10 vp/dose (V520) on Day 1, Week 4, and Week 26.
Per a letter dated 30-Aug-2005 all sites were notified that due to recruitment challenges enrollment would be halted as of 01-Oct-2005. Consequently, no participants were enrolled in the group MRKAd5 HIV-1 gag 1x10\^10 vp/dose. | 0 |
| Placebo Participants administered placebo to MRKAd5 HIV-1 gag vaccine (V520) on Day 1, Week 4, and Week 26. | 8 |
| Open Label Tetanus and Diptheria Toxoids Adsorbed Participants were to be administered open label tetanus and diptheria toxoids adsorbed (Td) at Day 1 only.
Per a letter dated 30-Aug-2005 all sites were notified that due to recruitment challenges enrollment would be halted as of 01-Oct-2005. Consequently, no participants were enrolled in this group. | 0 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Placebo | Total |
|---|---|---|---|
| Age, Customized | 41.4 years | 39.3 years | 40.4 years |
| Gender Female | 5 participants | 4 participants | 9 participants |
| Gender Male | 4 participants | 4 participants | 8 participants |
| Region of Enrollment United States | 9 participants | 8 participants | 17 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 6 / 8 |
| serious Total, serious adverse events | 2 / 9 | 2 / 8 |
Outcome results
Primary
Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE)
Serious and non serious clinical (systemic and injection-site AEs), and laboratory AEs were collected. Systemic and laboratory AEs reflect any unfavorable & unintended change in the structure, function, or chemistry of the body. Injection-site AEs include any swelling, redness, pain or tenderness at the injection site. Vaccine-related AEs are those determined by the investigator to be possibly, probably, or definitely related to the administration of the vaccine.
Time frame: up to Week 78 (52 weeks after boost injection) for systemic AEs, 29 days after any dose for laboratory AEs, and 5 days after any dose for injection-site AEs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With non-serious vaccine-related (VR) clinical AEs | 5 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With non-serious VR systemic AEs | 3 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With non-serious VR injection-site AEs | 3 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With serious VR clinical AEs | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With serious VR systemic AEs | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With serious VR injection-site AEs | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With non-serious VR laboratory AEs | 2 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With serious VR laboratory AEs | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to non-serious VR clinical AE | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to serious VR clinical AE | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to VR non-serious laboratory AE | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to VR serious laboratory AE | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to VR non-serious laboratory AE | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With non-serious vaccine-related (VR) clinical AEs | 1 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With non-serious VR laboratory AEs | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With non-serious VR systemic AEs | 1 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to serious VR clinical AE | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With non-serious VR injection-site AEs | 1 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With serious VR laboratory AEs | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | With serious VR clinical AEs | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to VR serious laboratory AE | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With serious VR systemic AEs | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | discontinued due to non-serious VR clinical AE | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Clinical (Systemic and Injection-site), and Laboratory Adverse Events (AE) | ---With serious VR injection-site AEs | 0 Participants |
Secondary
Immune Response by Levels of Unfractionated Gag-specific IFN-gamma Following a 3-dose Vaccine Regimen
Participants expressing HIV antigens (gag) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag-specific IFN-gamma were to be measured using an Enzyme Linked Immunospot Assay (ELISPOT), which measures spot forming cells per 10\^6 peripheral blood mononuclear cells (SFC per million PBMCs). No immunogenicity analyses were performed because the results from a previous study, V520-023 (NCT00095576), which used the same vaccine as the one used in this study (NCT00857311) proved it was not efficacious.
Time frame: Week 30 (4 weeks after boost injection)
Population: No analysis was performed.
Secondary
Number of Participants With Systemic and Laboratory Adverse Events (AE)
Adverse experiences collected include serious and non serious systemic AEs, injection-site AEs, and laboratory AEs. Systemic and laboratory AEs include any unfavorable & unintended change in the structure, function, or chemistry of the body. Injection-site AEs include any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to 5 days after any vaccine dose.
Time frame: up to Week 260 (234 weeks after boost injection) for systemic AEs, 29 days after any dose for laboratory AEs, and 5 days after any dose for injection-site AEs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious systemic AEs | 2 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious injection-site AEs | 0 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious systemic AEs | 8 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious laboratory AEs | 4 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious injection-site AEs | 3 Participants |
| MRKAd5 HIV-1 Gag Vaccine 1x10^9 vp/Dose | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious laboratory AEs | 0 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious laboratory AEs | 0 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious systemic AEs | 6 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious systemic AEs | 2 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious injection-site AEs | 1 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With serious injection-site AEs | 0 Participants |
| Placebo | Number of Participants With Systemic and Laboratory Adverse Events (AE) | With non-serious laboratory AEs | 1 Participants |