HIV-1, HIV Infections
Conditions
Keywords
HIV Seronegativity, Preventive Vaccine
Brief summary
The goal of this study is to understand the safety, tolerability and immunogenicity of the Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef Vaccine (MRKAd 5 HIV-1 gag/pol/nef) vaccine in healthy human volunteers compared to placebo. The study will also evaluate a number of dose levels and the necessity for and timing of booster injections.
Detailed description
The study will proceed in four stages. Following stages I, II and III, all subjects will have the Postdose 1 (PD1) clinical and laboratory safety data reviewed by the Safety Evaluation Committee (SEC). If these data are acceptable, the next stage will be initiated. * In Stage I, participants will be randomized to receive 3 doses of the 3x10\^9vp/dose level Trivalent vaccine or placebo. * In Stage II, participants will be randomized to receive 2 or 3 doses of the 3x10\^10vp/dose level Trivalent vaccine or placebo. * In Stage III, participants will be randomized to receive 3 doses of the Trivalent vaccine with titers of 1x10\^11vp/dose, 3x10\^6vp/dose, 3x10\^7vp/dose, or 3x10\^8vp/dose or placebo. * In Stage IV, participants will be randomized to all treatment groups. In addition, some participants will be randomized to an MRKAd 5 HIV-1 gag Monovalent vaccine. In this stage, participants will be pre-stratified by baseline Ad5 titers (=\<200, and \>200), to ensure an even distribution of participants with high and low Ad5 titers across the various treatment groups.
Interventions
OTHERComparator: Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine
Placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine.
BIOLOGICALMonovalent MRKAd5 HIV-1 gag vaccine (1x10^9 vp/dose)
Monovalent MRKAd5 HIV-1 gag vaccine (1x10\^9 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^6 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^6 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^7 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^7 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^8 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^8 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^9 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^9 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10^10 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^10 vp/dose)
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10^11 vp/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10\^11 vp/dose)
BIOLOGICALComparator: Placebo to MRKAd5 HIV-1 gag vaccine
Placebo to the MRKAd5 HIV-1 gag vaccine.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects 18 Years to 45 Years in Stages I-III and 18 Years to 50 Years in Stage IV. * Subject is in good general health * Subjects of reproductive potential agree to use acceptable method of birth control through study * Subject tests negative for Hepatitis B, Hepatitis C, and HIV
Exclusion criteria
* Subject has a recent history of fever at time of vaccination * Subject has received immune globulin or blood product 3 months prior to injection * Subject has been vaccinated with live virus vaccine 30 days prior to receipt of first dose * Subject has been vaccinated with inactivated vaccine with 14 days prior to receipt of first dose * Subject has a chronic medical condition that is considered progressive * Subject has history of malignancy * Subject weighs less than 105 lb. * Female subject is pregnant or breast feeding, Male subject is planning to impregnate during the first year of study * Subject has contraindication to intramuscular injection * Subject has a tattoo on the deltoid region of the arm or the injection of Depo-Provera * Subject is unlikely or unwilling to adhere to lower risk sex practices during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Experiences | up to 260 weeks after first vaccination | Adverse experiences (AE) collected include serious and non serious systemic AEs, and injection-site 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. |
| Number of Participants With Laboratory Adverse Experiences | up to 260 weeks after first vaccination | Laboratory AEs were based on a grading system considering the severity of abnormal laboratory values in participants and reflect any unfavorable and unintentional change in function, or chemistry of the body. All laboratory AEs were collected up to 29 days after any vaccine dose. |
| Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen | 4 weeks after booster injection | Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-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). |
| Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen | 4 weeks after booster injection | Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-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 (NCT00849680) proved it was not efficacious. |
Participant flow
Recruitment details
317 participants were randomized. 2 did not receive any study medication. Therefore, the safety population was 315.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2 or 3 doses of 1.0 mg of placebo to the MRKAd5 HIV-1 gag/pol/nef vaccine or 3 doses of placebo to the MRKAd5 HIV-1 gag vaccine injected intramuscularly. | 27 |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) 3 doses of 1.0 ml of the Monovalent MRKAd5 HIV-1 gag vaccine (1x10\^9 vp/dose) injected intramuscularly. | 13 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^6 vp/dose) injected intramuscularly. | 42 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^7 vp/dose) injected intramuscularly. | 42 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^8 vp/dose) injected intramuscularly. | 42 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^9 vp/dose) injected intramuscularly. | 42 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) 2 or 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (3x10\^10 vp/dose) injected intramuscularly. | 78 |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) 3 doses of 1.0 ml of Trivalent MRKAd5 HIV-1 gag/pol/nef vaccine (1x10\^11 vp/dose) injected intramuscularly. | 31 |
| Total | 317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 7 | 3 | 12 | 11 | 8 | 11 | 12 | 5 |
| Overall Study | Subject moved | 1 | 0 | 3 | 1 | 0 | 2 | 2 | 2 |
| Overall Study | Subject unable to comply with protocol | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 2 | 2 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 32.4 Years | 34.3 Years | 33.2 Years | 32.6 Years | 33.3 Years | 34.0 Years | 35.7 Years | 34.8 Years | 34.0 Years |
| Region of Enrollment United States | 27 participants | 13 participants | 42 participants | 42 participants | 42 participants | 42 participants | 78 participants | 31 participants | 317 participants |
| Sex: Female, Male Female | 19 Participants | 12 Participants | 21 Participants | 14 Participants | 17 Participants | 21 Participants | 31 Participants | 14 Participants | 149 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 21 Participants | 28 Participants | 25 Participants | 21 Participants | 47 Participants | 17 Participants | 168 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 26 | 13 / 13 | 35 / 41 | 38 / 42 | 35 / 42 | 39 / 42 | 74 / 78 | 31 / 31 |
| serious Total, serious adverse events | 1 / 26 | 2 / 13 | 2 / 41 | 3 / 42 | 4 / 42 | 3 / 42 | 7 / 78 | 1 / 31 |
Outcome results
Primary
Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 2-dose Vaccine Regimen
Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-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 (NCT00849680) proved it was not efficacious.
Time frame: 4 weeks after booster injection
Population: 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 (NCT00849680) proved it was not efficacious.
Primary
Immune Response by Levels of Unfractionated Gag, Pol, and Nef-specific IFN-gamma Following a 3-dose Vaccine Regimen
Participants expressing HIV antigens (gag, pol and nef) secrete antigen specific interferon-gamma (IFN-gamma). Levels of unfractionated gag, pol, and nef-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).
Time frame: 4 weeks after booster injection
Population: 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 (NCT00849680) proved it was not efficacious.
Primary
Number of Participants With Adverse Experiences
Adverse experiences (AE) collected include serious and non serious systemic AEs, and injection-site 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 260 weeks after first vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Experiences | With serious systemic AEs | 1 Participants |
| Placebo | Number of Participants With Adverse Experiences | With Injection site AEs | 6 Participants |
| Placebo | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 20 Participants |
| Placebo | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 9 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 13 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 2 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 17 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 36 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 2 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 33 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 3 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 18 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 4 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 35 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 22 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 37 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 3 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 23 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 68 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 57 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 7 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Adverse Experiences | With serious injection site AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Adverse Experiences | With serious systemic AEs | 1 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Adverse Experiences | With Injection site AEs | 29 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Adverse Experiences | With non-serious systemic AEs (NSAE) | 28 Participants |
Primary
Number of Participants With Laboratory Adverse Experiences
Laboratory AEs were based on a grading system considering the severity of abnormal laboratory values in participants and reflect any unfavorable and unintentional change in function, or chemistry of the body. All laboratory AEs were collected up to 29 days after any vaccine dose.
Time frame: up to 260 weeks after first vaccination
Population: Participants administered at least one dose of study vaccine. One participant who was lost to follow-up, and another one participant who discontinued as he comply with the protocol are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Placebo | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 10 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Monovalent MRKAd5 HIV-1 Gag Vaccine (1x10^9 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 5 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 12 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^6 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 6 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^7 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 12 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^8 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^9 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 17 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 29 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (3x10^10 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With non-serious laboratory AEs | 11 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Vaccine (1x10^11 vp/Dose) | Number of Participants With Laboratory Adverse Experiences | With serious laboratory AEs | 0 Participants |