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Investigation of V520 in an HIV Vaccine Proof-of-Concept Study (V520-023)

This study has been terminated.
Sponsor:
Collaborator:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00095576
First received: November 5, 2004
Last updated: October 29, 2014
Last verified: October 2014
Results First Received: July 20, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: AIDS
HIV Infections
Interventions: Biological: Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose)
Drug: Comparator: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

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.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.
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.

Participant Flow:   Overall Study
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
STARTED     1484     1495  
VACCINATED AT VISIT 2 (Dose 1)     1484     1495  
VACCINATED AT VISIT 4 (Dose 2)     1426     1443  
VACCINATED AT VISIT 7 (Dose 3)     1328     1361  
COMPLETED     9 [1]   14 [1]
NOT COMPLETED     1475     1481  
Adverse Event                 5                 3  
Lost to Follow-up                 233                 229  
Protocol Violation                 1                 0  
Withdrawal by Subject                 34                 47  
Option to switch to a rollover study                 1097                 1099  
Site terminated                 75                 67  
Subject moved                 30                 36  
[1] Subjects not completing entire study were eligible for observational long term follow up in V520-030



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo     Total  
Number of Participants  
[units: participants]
  1484     1495     2979  
Age  
[units: years]
Mean ± Standard Deviation
  29.9  ± 7.8     30.2  ± 8.13     30.1  ± 7.97  
Gender  
[units: participants]
     
Female     565     570     1135  
Male     919     925     1844  



  Outcome Measures
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1.  Primary:   Number of Participants With Clinical Adverse Experiences   [ Time Frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) ]

Measure Type Primary
Measure Title Number of Participants With Clinical Adverse Experiences
Measure Description

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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.

Measured Values
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
Number of Participants Analyzed  
[units: participants]
  1484     1495  
Number of Participants With Clinical Adverse Experiences  
[units: Participants]
   
With non-serious adverse events (NSAE)     1221     946  
With no non-serious adverse events     263     549  
With serious adverse events     19     17  
With no serious adverse events     1465     1478  

No statistical analysis provided for Number of Participants With Clinical Adverse Experiences



2.  Primary:   Number of Participants With Laboratory Adverse Experiences   [ Time Frame: Day 1 to Week 208 ]

Measure Type Primary
Measure Title Number of Participants With Laboratory Adverse Experiences
Measure Description

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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.

Measured Values
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
Number of Participants Analyzed  
[units: participants]
  1484     1495  
Number of Participants With Laboratory Adverse Experiences  
[units: Participants]
  0     0  

No statistical analysis provided for Number of Participants With Laboratory Adverse Experiences



3.  Primary:   Number of Participants With HIV-1 Infections   [ Time Frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) ]

Measure Type Primary
Measure Title Number of Participants With HIV-1 Infections
Measure Description 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
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.

Measured Values
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
Number of Participants Analyzed  
[units: participants]
  0     0  
Number of Participants With HIV-1 Infections          

No statistical analysis provided for Number of Participants With HIV-1 Infections



4.  Primary:   HIV-1 Viral Load in Infected Participants   [ Time Frame: Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) ]

Measure Type Primary
Measure Title HIV-1 Viral Load in Infected Participants
Measure Description 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)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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.
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.

Measured Values
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
Number of Participants Analyzed  
[units: participants]
  0     0  
HIV-1 Viral Load in Infected Participants          

No statistical analysis provided for HIV-1 Viral Load in Infected Participants




  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
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.
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.

Serious Adverse Events
    Trivalent MRKAd5 HIV-1 Gag/Pol/Nef     Placebo  
Total, serious adverse events      
# participants affected / at risk     19/1484 (1.28%)     17/1495 (1.14%)  
Blood and lymphatic system disorders      
Anemia aggravated      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Congenital, familial and genetic disorders      
Congenital cardiovascular anomaly      
# participants affected / at risk     0/1484 (0.00%)     2/1495 (0.13%)  
# events     0     2  
Hypoplastic left heart syndrome      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Unspecified congenital anomaly of heart      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Ventricular septal defect      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Gastrointestinal disorders      
Acute diarrhoea      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
General disorders      
Fever      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Rigors      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Hepatobiliary disorders      
Cholecystitis acute      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Immune system disorders      
Drug hypersensitivity      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Infections and infestations      
Appendicitis      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Gastroenteritis viral      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Pulmonary tuberculosis      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Shunt infection      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Staphylococcal abscess      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Vulval abscess      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Injury, poisoning and procedural complications      
Asbestosis      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Gun shot wound      
# participants affected / at risk     1/1484 (0.07%)     1/1495 (0.07%)  
# events     1     1  
Overdose      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Stab wound      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Traumatic brain injury      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Metabolism and nutrition disorders      
Dehydration      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Musculoskeletal and connective tissue disorders      
Low back pain      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Musculoskeletal pain      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Slipped disc      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Gastric cancer      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Uterine fibroids      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Nervous system disorders      
Headache      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Psychiatric disorders      
Depression      
# participants affected / at risk     1/1484 (0.07%)     1/1495 (0.07%)  
# events     1     1  
Depression aggravated      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Depressive episode      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Manic episode      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Polysubstance dependence      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Substance abuse      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Suicide attempt      
# participants affected / at risk     0/1484 (0.00%)     1/1495 (0.07%)  
# events     0     1  
Renal and urinary disorders      
Kidney stone      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Respiratory, thoracic and mediastinal disorders      
Exacerbation of asthma      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Pleural effusion      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Respiratory distress      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  
Vascular disorders      
Hypertension      
# participants affected / at risk     1/1484 (0.07%)     0/1495 (0.00%)  
# events     1     0  




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The DSMB (Data & Safety Monitoring Board) reviewed interim data which demonstrated that the investigational vaccine was not effective, and all vaccinations were halted. Long term follow up was available for participants in V520-030.


  More Information