Evaluating the Safety and Immune Response of a Prime-Boost HIV Vaccine Regimen in Healthy, HIV-Uninfected, Vaccinia-Naive Adults

NCT01571960 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 09411827
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

This study will test the safety and immune responses of a prime-boost regimen of two HIV vaccines- a DNA vaccine followed by a modified vaccinia Ankara (MVA) vaccine- in healthy, HIV-uninfected, vaccinia-naive adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (5)

• Frequency and severity of local injection site reactogenicity signs and symptoms

  Signs and symptoms include pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness.

  Measured within the initial 72-hour period following each vaccination visit (Days 0, 56, 112, 168, 224, and 303)

• Frequency and severity of systemic reactogenicity signs and symptoms and maximum severity of systemic symptoms

  Systemic reactogenicity signs and symptoms include fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, and arthralgia.

  Measured within the initial 72-hour period following each vaccination visit (Days 0, 56, 112, 168, 224, and 303)

• Distribution of values of safety laboratory measures: complete blood count (CBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and creatinine

  Group 1: Measured through Day 334; Group 2: Measured through Day 394; Group 3: Measured through Day 334

• Frequency of adverse events (AEs) categorized by MedDRA System Organ Class and MedDRA Preferred Term; severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting

  Group 1: Measured through Day 425; Group 2: Measured through Day 667; Group 3: Measured through Day 607

• Report of the number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation

  Group 1: Measured through Day 425; Group 2: Measured through Day 667; Group 3: Measured through Day 607

Secondary Outcomes (9)

• Frequency and magnitude of HIV-1 envelope (env)-specific binding antibody and isotypes

  Group 2: Measured at Day 317; Group 3: Measured at Day 238

• Frequency of neutralizing antibody responses to HIV-1

  Group 2: Measured at Day 317; Group 3: Measured at Day 238

• In individuals with neutralizing antibodies to HIV-1, neutralizing antibody titers (magnitude) and breadth of neutralizing activity

  Group 2: Measured at Day 317; Group 3: Measured at Day 238

• Frequency and magnitude of HIV-1 specific CD4+ and CD8+ T cell responses as measured by intracellular cytokine staining (ICS) at 2 weeks after the second vaccination for Groups 2 and 3

  Measured at Day 70

• Frequency and magnitude of HIV-1 specific CD4+ and CD8+ T cell responses as measured by ICS at 2 weeks after the last vaccination for Groups 2 and 3

  Group 2: Measured at Day 317; Group 3: Measured at Day 238

Study Arms (6)

Group 1: study vaccine

EXPERIMENTAL

Participants in this arm will receive a 0.3-mg dose injection of GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of MVA62B vaccine at Days 112, 168, and 224.

Biological: GEO-D03 DNA vaccine; Biological: MVA/HIV62B (MVA62B) vaccine

Group 1: placebo vaccine

PLACEBO COMPARATOR

Participants in this arm will receive injections of placebo for GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of placebo for MVA62B vaccine at Days 112, 168, and 224.

Biological: Placebo for GEO-D03 DNA; Biological: Placebo for MVA62B:

Group 2: study vaccine

EXPERIMENTAL

Participants in this arm will receive a 3-mg dose injection of GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of MVA62B vaccine at Days 112, 168, and 303.

Biological: GEO-D03 DNA vaccine; Biological: MVA/HIV62B (MVA62B) vaccine

Group 2: placebo vaccine

PLACEBO COMPARATOR

Participants in this arm will receive injections of placebo for GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of placebo for MVA62B vaccine at Days 112, 168, and 303.

Biological: Placebo for GEO-D03 DNA; Biological: Placebo for MVA62B:

Group 3: study vaccine

EXPERIMENTAL

Participants in this arm will receive a 3-mg dose injection of GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of MVA62B vaccine at Days 112 and 224.

Biological: GEO-D03 DNA vaccine; Biological: MVA/HIV62B (MVA62B) vaccine

Group 3: placebo vaccine

PLACEBO COMPARATOR

Participants in this arm will receive injections of placebo for GEO-D03 DNA vaccine at Days 0 and 56, followed by injections of placebo for MVA62B vaccine at Days 112 and 224.

Biological: Placebo for GEO-D03 DNA; Biological: Placebo for MVA62B:

Interventions

GEO-D03 DNA vaccine BIOLOGICAL

Either a 0.3-mg (Group 1: study vaccine) or 3-mg dose (Groups 2 and 3: study vaccine) administered as a 1-mL IM injection into the deltoid

Group 1: study vaccine; Group 2: study vaccine; Group 3: study vaccine

MVA/HIV62B (MVA62B) vaccine BIOLOGICAL

1 x 10\^8-TCID50 dose of MVA62B vaccine, administered as a 1-mL IM injection into the deltoid

Group 1: study vaccine; Group 2: study vaccine; Group 3: study vaccine

Placebo for GEO-D03 DNA BIOLOGICAL

Administered as a 1-mL IM injection into the deltoid

Group 1: placebo vaccine; Group 2: placebo vaccine; Group 3: placebo vaccine

Placebo for MVA62B: BIOLOGICAL

Administered as a 1-mL IM injection into the deltoid

Group 1: placebo vaccine; Group 2: placebo vaccine; Group 3: placebo vaccine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: participant demonstrates understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks, amenable to HIV risk-reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years following initial study injection
• Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual contacts for safety surveillance)
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• Assessed by the clinic staff as being at low risk of HIV infection
• Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, or greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell (WBC) count of 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 cells/mm\^3
• Remaining differential either within institutional normal range or with site physician approval
• Platelet level of 125,000 to 550,000/mm\^3
• Chemistry panel: ALT, AST, alkaline phosphatase, and creatinine values less than or equal to institutional upper limits of normal

You may not qualify if:

• Vaccinia (smallpox) vaccine determined by (1) clinical evidence of vaccinia scarification; (2) self-reported history of vaccinia vaccination; (3) date of birth; or (4) U.S. military service prior to 1989 or after December 2002 (not excluded: a participant born before 1975, or with past U.S. military service, who self-reports he/she did not receive vaccinia vaccine and has no evidence of scarification)
• Untreated or incompletely treated syphilis infection
• HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 094 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 094 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 094 PSRT on a case-by-case basis.
• Immunosuppressive medications received within 168 days before first vaccination. Not excluded: (1) corticosteroid nasal spray for allergic rhinitis; (2) topical corticosteroids for mild, uncomplicated dermatitis; or (3) oral/parenteral corticosteroids given for non-chronic conditions not expected to recur (length of therapy 10 days or less with completion at least 30 days prior to enrollment)
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 60 days before first vaccination
• Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• 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 094 study
• Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• 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. A clinically significant condition or process includes but is not limited to:
• A process that would affect the immune response

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• GeoVax, Inc.: collaborator

Study Sites (4)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Related Publications (3)

• Goepfert PA, Elizaga ML, Sato A, Qin L, Cardinali M, Hay CM, Hural J, DeRosa SC, DeFawe OD, Tomaras GD, Montefiori DC, Xu Y, Lai L, Kalams SA, Baden LR, Frey SE, Blattner WA, Wyatt LS, Moss B, Robinson HL; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2011 Mar 1;203(5):610-9. doi: 10.1093/infdis/jiq105. Epub 2011 Jan 31.

  PMID: 21282192 BACKGROUND

• Pantaleo G, Esteban M, Jacobs B, Tartaglia J. Poxvirus vector-based HIV vaccines. Curr Opin HIV AIDS. 2010 Sep;5(5):391-6. doi: 10.1097/COH.0b013e32833d1e87.

  PMID: 20978379 BACKGROUND

• Buchbinder SP, Grunenberg NA, Sanchez BJ, Seaton KE, Ferrari G, Moody MA, Frahm N, Montefiori DC, Hay CM, Goepfert PA, Baden LR, Robinson HL, Yu X, Gilbert PB, McElrath MJ, Huang Y, Tomaras GD; HIV Vaccine Trials Network (HVTN) 094 Study Group. Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults. PLoS One. 2017 Jul 20;12(7):e0179597. doi: 10.1371/journal.pone.0179597. eCollection 2017.

  PMID: 28727817 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Vaccines

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Susan Buchbinder

  San Francisco Department of Public Health

  STUDY CHAIR

• Christine (Mhorag) Hay

  University of Rochester

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: April 5, 2012
• Study Start: April 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: January 1, 2016
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (4)