AIDS, HIV Infections
Conditions
Brief summary
This study will test the safety and efficacy of an investigational Human Immunodeficiency Virus (HIV) vaccine. Efficacy will be measured by either prevention of HIV infection or control of HIV viral load in subjects who become HIV infected. On September 18, 2007 the Protocol V520-023 DSMB (Data & Safety Monitoring Board) reviewed data from a planned interim analysis. These data demonstrated that the investigational vaccine candidate was not effective, and all vaccinations in the study were halted. Participants were encouraged to continue to come to the clinic for scheduled visits and ongoing risk reduction counseling since the vaccine was not effective.
Detailed description
No further treatment was given in V520-023, however participants were followed. V520-023 protocol ended earlier than originally planned per protocol and participants (HIV infected and uninfected) had the option of participating in an observational long term follow up protocol called V520-030/HVTN 504, which served as an extension of V520-023 and would continue through the end of 2009.
Interventions
BIOLOGICALTrivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose)
Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10\^10 adenovirus genomes \[ad-vg\]/dose). This dose is equivalent to 3x10\^10 vp/dose used in study V520-016.
DRUGComparator: placebo
Placebo to Trivalent MRKAd5 HIV-1 gag/pol/nef in three 1 mL doses at Day 1, Week 4, and Week 26 administered intramuscularly.
Sponsors
HIV Vaccine Trials Network
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
* Healthy, HIV seronegative adults at high risk of acquiring HIV infection * Cannot have previously received an investigational vaccine
Exclusion criteria
* In a monogamous relationship with an HIV-1 seronegative partner for \> 1 year * History of anaphylaxis and/or allergy to vaccine components, including Tris buffer, MgCl2, and polysorbate 80 (TWEEN) * Received an immune globulin or blood derived products 3 months before injection with the first dose of vaccine/placebo or scheduled within 14 days after injection * Previously vaccinated with a live virus vaccine within 30 days before injection with the first dose of vaccine or scheduled within 14 days after injection * Previously vaccinated with an inactivated vaccine within 5 days before injection with the first dose of vaccine or scheduled within 14 days after injection * Known history of immunodeficiency * History of malignancy (with some exceptions) * Contraindication to intramuscular (IM) injection such as anticoagulant therapy or thrombocytopenia * Female subject who is pregnant or breast feeding, or expecting to conceive or donate eggs through Week 30 of the study * Male subject who is planning to impregnate or provide sperm donation through Week 30 of the study * Previously received an investigational HIV vaccine * Has active drug or alcohol abuse or dependence that would interfere with adherence to study requirements, or endanger the subject's health while on the study * Has a condition that might endanger the subject's health or interfere with the evaluation of the study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Adverse Experiences | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) | Number of participants with non-serious AEs with an incidence cut-off of 5% (\>5% in at least one treatment group) and number of participants with \>1 SAE following administration of study vaccine. AEs collected include serious and non-serious systemic AEs, and injection-site AEs. All systemic AEs were collected up to 14 days after any vaccine dose, and serious AEs were collected for the entire study period (up to Week 210). Injection-site AEs are any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to Day 4 after any vaccine dose. |
| Number of Participants With Laboratory Adverse Experiences | Day 1 to Week 208 | Number of participants with laboratory adverse experiences with an incidence cut-off of 5% (events occurring \> 5% in at least one treatment group) following administration of the first dose of study vaccine. 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 14 days after any vaccine dose. |
| Number of Participants With HIV-1 Infections | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) | The number of participants with HIV-1 infections was to be determined with a periodic HIV-1 screening test to detect antibodies to recombinant HIV-1 envelope protein in the participants' serum. |
| HIV-1 Viral Load in Infected Participants | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) | Plasma HIV-1 viral RNA was to be measured using a ribonucleic acid polymerase chain reaction (RNA PCR) on the last archived sample, and at Weeks 1, 2, 8, 12, and 26 post-HIV-1 infection, and subsequently every 6 months. |
Participant flow
Recruitment details
3000 participants were enrolled and randomized in the study. However, only 2979 received study vaccination, and are included in the started population. V520-023 was terminated early based on findings at a planned interim analysis and subjects were encouraged to participate in the V520-030 rollover study for additional long term follow up.
Participants by arm
| Arm | Count |
|---|---|
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10\^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. | 1,484 |
| Placebo Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. | 1,495 |
| Total | 2,979 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lost to Follow-up | 233 | 229 |
| Overall Study | Option to switch to a rollover study | 1,097 | 1,099 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Site terminated | 75 | 67 |
| Overall Study | Subject moved | 30 | 36 |
| Overall Study | Withdrawal by Subject | 34 | 47 |
Baseline characteristics
| Characteristic | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 29.9 years STANDARD_DEVIATION 7.8 | 30.2 years STANDARD_DEVIATION 8.13 | 30.1 years STANDARD_DEVIATION 7.97 |
| Sex: Female, Male Female | 565 Participants | 570 Participants | 1135 Participants |
| Sex: Female, Male Male | 919 Participants | 925 Participants | 1844 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,221 / 1,484 | 946 / 1,495 |
| serious Total, serious adverse events | 19 / 1,484 | 17 / 1,495 |
Outcome results
Primary
HIV-1 Viral Load in Infected Participants
Plasma HIV-1 viral RNA was to be measured using a ribonucleic acid polymerase chain reaction (RNA PCR) on the last archived sample, and at Weeks 1, 2, 8, 12, and 26 post-HIV-1 infection, and subsequently every 6 months.
Time frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
Population: An interim analysis for this study showed that the MRK Ad5 HIV-1 gag/pol/nef vaccine used in this study was not efficacious; therefore, this outcome measure was not analyzed and only a high level summary of the safety data was performed.
Primary
Number of Participants With Clinical Adverse Experiences
Number of participants with non-serious AEs with an incidence cut-off of 5% (\>5% in at least one treatment group) and number of participants with \>1 SAE following administration of study vaccine. AEs collected include serious and non-serious systemic AEs, and injection-site AEs. All systemic AEs were collected up to 14 days after any vaccine dose, and serious AEs were collected for the entire study period (up to Week 210). Injection-site AEs are any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to Day 4 after any vaccine dose.
Time frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Number of Participants With Clinical Adverse Experiences | With non-serious adverse events (NSAE) | 1221 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Number of Participants With Clinical Adverse Experiences | With no non-serious adverse events | 263 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Number of Participants With Clinical Adverse Experiences | With serious adverse events | 19 Participants |
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Number of Participants With Clinical Adverse Experiences | With no serious adverse events | 1465 Participants |
| Placebo | Number of Participants With Clinical Adverse Experiences | With no serious adverse events | 1478 Participants |
| Placebo | Number of Participants With Clinical Adverse Experiences | With non-serious adverse events (NSAE) | 946 Participants |
| Placebo | Number of Participants With Clinical Adverse Experiences | With serious adverse events | 17 Participants |
| Placebo | Number of Participants With Clinical Adverse Experiences | With no non-serious adverse events | 549 Participants |
Primary
Number of Participants With HIV-1 Infections
The number of participants with HIV-1 infections was to be determined with a periodic HIV-1 screening test to detect antibodies to recombinant HIV-1 envelope protein in the participants' serum.
Time frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)
Population: An interim analysis for this study showed that the MRK Ad5 HIV-1 gag/pol/nef vaccine used in this study was not efficacious; therefore, this outcome measure was not analyzed and only a high level summary of the safety data was performed.
Primary
Number of Participants With Laboratory Adverse Experiences
Number of participants with laboratory adverse experiences with an incidence cut-off of 5% (events occurring \> 5% in at least one treatment group) following administration of the first dose of study vaccine. 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 14 days after any vaccine dose.
Time frame: Day 1 to Week 208
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Number of Participants With Laboratory Adverse Experiences | 0 Participants |
| Placebo | Number of Participants With Laboratory Adverse Experiences | 0 Participants |