Safety and Efficacy of a Three-Dose Regimen of an Adenoviral HIV Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in HIV Uninfected South African Adults

NCT00413725 | Completed Phase 2

• 3 other identifiers: HVTN 503 (Phambili)10392HVTN 503
• Study Type: interventional
• Target: 801
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the safety, efficacy, and tolerability of a three-dose regimen of an adenovirus-based HIV-1 vaccine in healthy South African adults.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine; Adenovirus

Outcome Measures

Primary Outcomes (2)

• Acquisition of HIV-1 infection

  Throughout study

• Viral load set point (HIV-1 RNA) in study participants who become HIV infected

  At approximately 3 months postdiagnosis

Secondary Outcomes (4)

• Acquisition of HIV-1 infection among participants with baseline Ad5 neutralizing antibody titers of 200 or less

  Throughout study

• Viral load setpoint in such study participants

  Throughout study

• Durability of effect of vaccine on suppression of HIV-1 viral RNA and preservation of CD4 counts

  At 18 months after diagnosis of HIV infection

• One time questionnaire evaluating impact of discontinuation of vaccination on participants

  After vaccination discontinuation

Study Arms (2)

1

EXPERIMENTAL

Three doses of MRKAd5 HIV-1 gag/pol/nef vaccine

Biological: MRKAd5 HIV-1 gag/pol/nef

2

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

MRKAd5 HIV-1 gag/pol/nef BIOLOGICAL

Experimental Clade-B based Adenovirus serotype 5 HIV-1 gag/pol/nef vaccine

1

Placebo OTHER

Placebo

2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 and -2 negative
• Good general health
• ALT less than 2.6 times the upper limit of normal (ULN)
• Sexually active within the 6 months prior to study entry
• Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed during the study
• Demonstrate understanding of the study
• Willing to receive HIV test results
• Female participants must be willing to use acceptable forms of contraception, or not be of reproductive potential. More information about this criterion can be found in the protocol.

You may not qualify if:

• Adenovirus 5 titer greater than 200, once enrollment of participants in this stratum has been completed
• HIV vaccines in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
• Immunosuppressive medications within 168 days prior to first study vaccination. Participants who have used corticosteroid nasal sprays for allergic rhinitis or topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
• Blood products within 90 days prior to first study vaccination
• Immunoglobulin within 90 days prior to first study vaccination
• Live attenuated vaccines within 30 days prior to first study vaccination
• Investigational research agents within 30 days prior to first study vaccination
• Medically indicated subunit or killed vaccines within 5 days prior to first study vaccination OR scheduled to receive such vaccines within 14 days after first study vaccination
• Allergy treatment with antigen injections within 30 days prior to first study vaccination
• Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
• Any medical, psychiatric, or job-related responsibility that would interfere with the study. More information about this criterion can be found in the protocol.
• Any concern that, in the opinion of the investigator, may interfere with a participant's completion of the post-vaccination symptom log
• History of anaphylaxis or allergy to any of the vaccine's components
• Autoimmune disease
• Immunodeficiency

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator

Study Sites (5)

Soweto HVTN CRS

Johannesburg, Gauteng, 1862, South Africa

Location

MedCRU CRS

Pretoria, Gauteng, 0204, South Africa

Location

eThekwini CRS

Durban, KwaZulu-Natal, 4001, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

CAPRISA Aurum CRS

Klerksdorp, 2571, South Africa

Location

Related Publications (8)

• Morgan C, Bailer R, Metch B, Koup R, Paranjape RS, Vardas E, Pape JW, Figueroa JP, Barroso, P, Kalichman A, Jaspan H, Lama J, Jack N, Russell N. International seroprevalence of neutralizing antibodies against adenovirus serotypes 5 and 35. AIDS Vaccine 2005. Montreal, September 7, 2005.

  BACKGROUND

• Shiver JW, Emini EA. Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004;55:355-72. doi: 10.1146/annurev.med.55.091902.104344.

  PMID: 14746526 BACKGROUND

• Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17;415(6869):331-5. doi: 10.1038/415331a.

  PMID: 11797011 BACKGROUND

• Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, Mlisana K, Metch B, de Bruyn G, Latka MH, Roux S, Mathebula M, Naicker N, Ducar C, Carter DK, Puren A, Eaton N, McElrath MJ, Robertson M, Corey L, Kublin JG; HVTN 503/Phambili study team. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 2011 Jul;11(7):507-15. doi: 10.1016/S1473-3099(11)70098-6. Epub 2011 May 11.

  PMID: 21570355 RESULT

• Leitman EM, Hurst J, Mori M, Kublin J, Ndung'u T, Walker BD, Carlson J, Gray GE, Matthews PC, Frahm N, Goulder PJ. Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02. J Infect Dis. 2016 Aug 1;214(3):379-89. doi: 10.1093/infdis/jiw093. Epub 2016 Mar 6.

  PMID: 26951820 DERIVED

• Moodie Z, Metch B, Bekker LG, Churchyard G, Nchabeleng M, Mlisana K, Laher F, Roux S, Mngadi K, Innes C, Mathebula M, Allen M, Bentley C, Gilbert PB, Robertson M, Kublin J, Corey L, Gray GE. Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men. PLoS One. 2015 Sep 14;10(9):e0137666. doi: 10.1371/journal.pone.0137666. eCollection 2015.

  PMID: 26368824 DERIVED

• Gray GE, Moodie Z, Metch B, Gilbert PB, Bekker LG, Churchyard G, Nchabeleng M, Mlisana K, Laher F, Roux S, Mngadi K, Innes C, Mathebula M, Allen M, McElrath MJ, Robertson M, Kublin J, Corey L; HVTN 503/Phambili study team. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study. Lancet Infect Dis. 2014 May;14(5):388-96. doi: 10.1016/S1473-3099(14)70020-9. Epub 2014 Feb 20.

  PMID: 24560541 DERIVED

• Latka MH, Fielding K, Gray GE, Bekker LG, Nchabeleng M, Mlisana K, Nielson T, Roux S, Mkhize B, Mathebula M, Naicker N, de Bruyn G, Kublin J, Churchyard GJ; HVTN 503 Phambili study team. Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women. PLoS One. 2012;7(4):e31387. doi: 10.1371/journal.pone.0031387. Epub 2012 Apr 19.

  PMID: 22532824 DERIVED

MeSH Terms

Conditions

HIV Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; DNA Virus Infections

Study Officials

• Glenda Gray, MD

  Chris Hani Baragwanath Hospital

  STUDY CHAIR

• James Kublin, MD, MPH

  Fred Hutchinson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2006
• First Posted: December 20, 2006
• Study Start: January 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

ZA (5)