Safety of and Immune Response to Prime/Boost Vaccine Regimens in Healthy, HIV-1 Uninfected, Ad5 Seronegative Adults

NCT00961883 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 0785U01AI068614
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Investigators will examine the safety of and immune responses to two vaccines expressing synthetic HIV proteins: NYVAC-B (a poxvirus), and rAd5 (an adenovirus). The study will compare responses in participants receiving NYVAC-B first, and rAd5 later, to those who receive rAd5 first, and NYVAC-B later. A different dose of rAd5 will be tested in each group.

Conditions

HIV Infections

Keywords

HIV; Vaccine; HIV Seronegativity; Preventive Vaccine

Outcome Measures

Primary Outcomes (1)

• Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse events and serious adverse events meeting expedited adverse (EAE) criteria

  Throughout study

Secondary Outcomes (1)

• Magnitude and frequency of T-cell response as measured by ELISpot and/or intracellular cytokine staining (ICS) assay 2 weeks post 4th vaccination

  At 2 Weeks following 4th Vaccination

Study Arms (4)

1

EXPERIMENTAL

Thirty participants will receive injections in the following order: NYVAC-B for injections one and two, placebo for injection three, and rAd5 for the fourth and final injection. Two participants in this group will receive placebo vaccines only.

Biological: NYVAC-B; Biological: Placebo; Biological: rAd5

2

EXPERIMENTAL

Fifteen participants will receive injections in the following order: rAd5 for injection one, placebo for injection two, and NYVAC-B for injections three and four. One participant in this group will receive placebo vaccines only.

Biological: NYVAC-B; Biological: Placebo; Biological: rAd5

3

EXPERIMENTAL

Fifteen participants will receive injections in the following order: rAd5 for injection one, placebo for injection two, and NYVAC-B for injections three and four. One participant in this group will receive placebo vaccines only.

Biological: NYVAC-B; Biological: Placebo; Biological: rAd5

4

EXPERIMENTAL

Fifteen participants will receive injections in the following order: rAd5 for injection one, placebo for injection two, and NYVAC-B for injections three and four. One participant in this group will receive placebo vaccines only.

Biological: NYVAC-B; Biological: Placebo; Biological: rAd5

Interventions

NYVAC-B BIOLOGICAL

New York Vaccinia (NYVAC) vector for HIV-1, delivered intramuscularly by injection at a dose of 1 x 10 \^7 PFU

1; 2; 3; 4

Placebo BIOLOGICAL

Sodium Chloride for injection, delivered intramuscularly

1; 2; 3; 4

rAd5 BIOLOGICAL

Recombinant adenoviral serotype 5 (rAd5) vector vaccine, delivered by injection intramuscularly at a dose of 1 x 10\^10 PFU

1; 4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide informed consent
• Assessment of understanding, including understanding of the Step Study results
• Willingness to receive HIV test results
• Amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Assessed by clinic staff as being "low risk" for HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment. More information on this criterion is in the study protocol.
• Good general health
• Neutralizing antibody titers of Ad5 less than 1:18
• Hemoglobin count of 11.0 g/dL or more for female volunteers, and 13.0 g/dL or more for male volunteers
• White blood cell count of 3300 to 12000 cells/mm\^3
• Total lymphocyte count of 800 cells/mm\^3 or more
• Remaining differential either within institutional normal range or with site physician approval
• Platelets in the range of 125,000 to 550,000/mm\^3
• Chemistry panel: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and creatinine values less than or equal to the institutional upper limits of normal
• HIV-uninfected
• Negative Hepatitis B surface antigen (HBsAg)

You may not qualify if:

• Excessive alcohol use or chronic marijuana use, or any other illicit drug use within the 12 months prior to enrollment
• History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, within the 12 months prior to enrollment
• HIV vaccine received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, documentation of the identity of the study control/placebo must be provided to the HVTN 078 PSRT, who will determine eligibility on a case-by-case basis.
• Immunosuppressive medications received within 168 days before first vaccination
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 60 days before first vaccination
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after first injection
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Investigational research agents received within 30 days before first vaccination
• Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 078 study
• Current anti-tuberculosis (TB) prophylaxis or therapy
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion is in the study protocol.
• Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent
• Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain

Sponsors & Collaborators

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

Study Sites (2)

BH10/513

Lausanne, 1011, Switzerland

Location

BT06/614

Lausanne, 1011, Switzerland

Location

Related Publications (5)

• Gomez CE, Najera JL, Jimenez EP, Jimenez V, Wagner R, Graf M, Frachette MJ, Liljestrom P, Pantaleo G, Esteban M. Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol-Nef proteins of clade B. Vaccine. 2007 Apr 12;25(15):2863-85. doi: 10.1016/j.vaccine.2006.09.090. Epub 2006 Oct 16.

  PMID: 17113200 BACKGROUND

• Harari A, Bart PA, Stohr W, Tapia G, Garcia M, Medjitna-Rais E, Burnet S, Cellerai C, Erlwein O, Barber T, Moog C, Liljestrom P, Wagner R, Wolf H, Kraehenbuhl JP, Esteban M, Heeney J, Frachette MJ, Tartaglia J, McCormack S, Babiker A, Weber J, Pantaleo G. An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med. 2008 Jan 21;205(1):63-77. doi: 10.1084/jem.20071331. Epub 2008 Jan 14.

  PMID: 18195071 BACKGROUND

• Liu J, O'Brien KL, Lynch DM, Simmons NL, La Porte A, Riggs AM, Abbink P, Coffey RT, Grandpre LE, Seaman MS, Landucci G, Forthal DN, Montefiori DC, Carville A, Mansfield KG, Havenga MJ, Pau MG, Goudsmit J, Barouch DH. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature. 2009 Jan 1;457(7225):87-91. doi: 10.1038/nature07469. Epub 2008 Nov 9.

  PMID: 18997770 BACKGROUND

• Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G. Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog. 2021 Nov 29;17(11):e1010016. doi: 10.1371/journal.ppat.1010016. eCollection 2021 Nov.

  PMID: 34843602 DERIVED

• Bart PA, Huang Y, Karuna ST, Chappuis S, Gaillard J, Kochar N, Shen X, Allen MA, Ding S, Hural J, Liao HX, Haynes BF, Graham BS, Gilbert PB, McElrath MJ, Montefiori DC, Tomaras GD, Pantaleo G, Frahm N. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial. J Clin Invest. 2014 Nov;124(11):4843-56. doi: 10.1172/JCI75894. Epub 2014 Oct 1.

  PMID: 25271627 DERIVED

MeSH Terms

Conditions

HIV 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

Study Officials

• Giuseppe Pantaleo

  CTU Lausanne

  STUDY CHAIR

• Pierre-Alexandre Bart, MD

  Lausanne CRS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2009
• First Posted: August 19, 2009
• Study Start: August 1, 2009
• Primary Completion: January 1, 2013
• Last Updated: September 6, 2013

Record last verified: 2013-09

Locations

CH (2)