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:

Merck

ClinicalTrials.gov Identifier:

NCT00095576

First received: November 5, 2004

Last updated: August 25, 2011

Last verified: August 2011

History of Changes

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.

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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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) ]

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2. Primary:

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

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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) ]

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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) ]

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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 [units: Viral genome copies/mL] Mean ± Standard Deviation

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

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:

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.

Limitations and Caveats

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.

Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck, Sharp & Dohme
e-mail: ClinicalTrialsDisclosure@merck.com

Publications:

Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; the Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. Epub 2008 Nov 13.

Publications automatically indexed to this study:

Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, del Rio C, Casapia M, Santiago S, Gilbert P, Corey L, Robertson MN; Step/HVTN 504 Study Team. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). J Infect Dis. 2012 Jul 15;206(2):258-66. Epub 2012 May 4.

Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, Mark KE, Casapia M, Mehrotra DV, Buchbinder SP, Corey L; NIAID HIV Vaccine Trials Network. Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the step study). J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):238-44.

Fitzgerald DW, Janes H, Robertson M, Coombs R, Frank I, Gilbert P, Loufty M, Mehrotra D, Duerr A; Step Study Protocol Team. An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study). J Infect Dis. 2011 Mar 15;203(6):765-72.

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00095576 History of Changes
Obsolete Identifiers:	NCT00770549
Other Study ID Numbers:	V520-023, 2004_091
Study First Received:	November 5, 2004
Results First Received:	July 20, 2011
Last Updated:	August 25, 2011
Health Authority:	United States: Food and Drug Administration

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