Trial Outcomes & Findings for Investigation of V520 in an HIV Vaccine Proof-of-Concept Study (V520-023) (NCT NCT00095576)

NCT ID: NCT00095576

Last Updated: 2015-10-06

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3000 participants

Primary outcome timeframe

Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants)

Results posted on

2015-10-06

Participant Flow

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.

Participant milestones

Participant milestones
Measure
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.
Overall Study
STARTED
1484
1495
Overall Study
VACCINATED AT VISIT 2 (Dose 1)
1484
1495
Overall Study
VACCINATED AT VISIT 4 (Dose 2)
1426
1443
Overall Study
VACCINATED AT VISIT 7 (Dose 3)
1328
1361
Overall Study
COMPLETED
9
14
Overall Study
NOT COMPLETED
1475
1481

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Overall Study
Adverse Event
5
3
Overall Study
Lost to Follow-up
233
229
Overall Study
Protocol Violation
1
0
Overall Study
Withdrawal by Subject
34
47
Overall Study
Option to switch to a rollover study
1097
1099
Overall Study
Site terminated
75
67
Overall Study
Subject moved
30
36

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Trivalent MRKAd5 HIV-1 Gag/Pol/Nef
n=1484 Participants
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
n=1495 Participants
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
n=2979 Participants
Total of all reporting groups
Age, Continuous
29.9 years
STANDARD_DEVIATION 7.8 • n=5 Participants
30.2 years
STANDARD_DEVIATION 8.13 • n=7 Participants
30.1 years
STANDARD_DEVIATION 7.97 • n=5 Participants
Sex: Female, Male
Female
565 Participants
n=5 Participants
570 Participants
n=7 Participants
1135 Participants
n=5 Participants
Sex: Female, Male
Male
919 Participants
n=5 Participants
925 Participants
n=7 Participants
1844 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Trivalent MRKAd5 HIV-1 Gag/Pol/Nef
n=1484 Participants
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
n=1495 Participants
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.
Number of Participants With Clinical Adverse Experiences
With non-serious adverse events (NSAE)
1221 Participants
946 Participants
Number of Participants With Clinical Adverse Experiences
With no non-serious adverse events
263 Participants
549 Participants
Number of Participants With Clinical Adverse Experiences
With serious adverse events
19 Participants
17 Participants
Number of Participants With Clinical Adverse Experiences
With no serious adverse events
1465 Participants
1478 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Trivalent MRKAd5 HIV-1 Gag/Pol/Nef
n=1484 Participants
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
n=1495 Participants
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.
Number of Participants With Laboratory Adverse Experiences
0 Participants
0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Trivalent MRKAd5 HIV-1 Gag/Pol/Nef

Serious events: 19 serious events
Other events: 1221 other events
Deaths: 0 deaths

Placebo

Serious events: 17 serious events
Other events: 946 other events
Deaths: 0 deaths

Serious adverse events

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

Other adverse events

Other adverse events
Measure
Trivalent MRKAd5 HIV-1 Gag/Pol/Nef
n=1484 participants at risk
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
n=1495 participants at risk
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.
Gastrointestinal disorders
Diarrhoea
10.5%
156/1484 • Number of events 195
9.9%
148/1495 • Number of events 182
Gastrointestinal disorders
Nausea
6.3%
94/1484 • Number of events 114
5.0%
75/1495 • Number of events 87
General disorders
Fatigue
11.5%
170/1484 • Number of events 218
8.0%
120/1495 • Number of events 149
General disorders
Fever
25.3%
376/1484 • Number of events 631
20.7%
309/1495 • Number of events 548
General disorders
General body pain
5.1%
76/1484 • Number of events 98
1.5%
23/1495 • Number of events 26
General disorders
Injection site erythema
21.4%
317/1484 • Number of events 448
9.6%
143/1495 • Number of events 197
General disorders
Injection site pain
64.8%
961/1484 • Number of events 1862
31.8%
475/1495 • Number of events 702
General disorders
Injection site swelling
22.7%
337/1484 • Number of events 511
7.7%
115/1495 • Number of events 149
General disorders
Injection site tenderness
18.3%
271/1484 • Number of events 374
5.4%
81/1495 • Number of events 92
Nervous system disorders
Headache
31.1%
461/1484 • Number of events 734
26.4%
394/1495 • Number of events 631
Respiratory, thoracic and mediastinal disorders
Sore throat
5.6%
83/1484 • Number of events 96
5.6%
83/1495 • Number of events 90

Additional Information

Senior Vice President, Global Clinical Development

Merck, Sharp & Dohme

Results disclosure agreements

  • Principal investigator is a sponsor employee As this study is part of a multicenter trial, publications derived from this study should include input from the principal investigator, his/her colleagues, the other investigators in this trial, and SPONSOR personnel. The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. SPONSOR review can be expedited to meet publication guidelines.
  • Publication restrictions are in place

Restriction type: OTHER