Evaluating the Safety and Immune Response to an HIV Vaccine in Healthy, HIV-Uninfected Adults Who Have Participated in Previous HIV Vaccine Clinical Trials and in Adults Who Have Not Participated in Previous HIV Vaccine Clinical Trials

NCT01376726 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 08811779
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety and immune response to an HIV vaccine in healthy, HIV-uninfected adults who have participated in a previous HIV vaccine clinical trial and in healthy, HIV-uninfected adults who have not participated in a previous HIV vaccine clinical trial.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (6)

• Frequency of severe local and systemic reactogenicity signs and symptoms

  Measured within the first 3 days after vaccination

• Summary reports of the frequency of adverse events (AEs) by group, by body system, MedDRA preferred term, severity, and assessed relationship to study product

  Measured through 12 months post last vaccination

• All serious adverse events (SAEs)

  Measured through 12 months post last vaccination

• Laboratory measures of safety at baseline and following vaccinations: descriptive analyses of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine

  Measured through 3 months post last vaccination

• Neutralizing antibody titers to SF162 and TV1

  Measured through 6 months post last vaccination

• Neutralizing antibody titers and breadth against heterologous primary isolates

  Measured through 6 months post last vaccination

Secondary Outcomes (4)

• SF162 Env-specific non-neutralizing antibodies and TV1 Env-specific antibodies as determined by multiplex antibody assays

  Measured through 6 months post last vaccination

• ConS gp140 specific IgG subclass characterization (IgG1- IgG4) and IgA measurement by custom HIV-1 multiplex assay

  Measured through 6 months post last vaccination

• Intracellular cytokine staining to evaluate polyfunctional cytokine responses by antigen-specific CD4 T cells

  Measured through 6 months post last vaccination

• Lymphoproliferation of antigen-specific CD4 T cells by carboxyfluorescein diacetate succinimidyl ester (CFSE) assay

  Measured through 6 months post last vaccination

Study Arms (2)

Previous HIV Vaccine Trial Participants (Group 1)

EXPERIMENTAL

Participants will receive the study vaccine administered as one 0.5 mL intramuscular injection (IM) in either deltoid at baseline and Month 6. Participants in the study extension will receive an additional injection of the study vaccine approximately 14 to 20 months after their second (Month 6) vaccination.

Biological: Sub C gp140 Vaccine; Biological: MF59C.1 Adjuvant

No Previous HIV Vaccine Trial (Group 2)

EXPERIMENTAL

Participants will receive the study vaccine administered as one 0.5 mL IM in either deltoid at baseline and Month 6. Participants in the study extension will receive an additional injection of the study vaccine approximately 14 to 20 months after their second (Month 6) vaccination.

Biological: Sub C gp140 Vaccine; Biological: MF59C.1 Adjuvant

Interventions

Sub C gp140 Vaccine BIOLOGICAL

Sub C gp140 100 mcg will be combined with MF59C.1 and administered as one injection (0.5 mL) IM in either deltoid at baseline and Month 6. Participants in the study extension will receive an additional injection of the study vaccine approximately 14 to 20 months after their second (Month 6) vaccination.

No Previous HIV Vaccine Trial (Group 2); Previous HIV Vaccine Trial Participants (Group 1)

MF59C.1 Adjuvant BIOLOGICAL

Sub C gp140 100 mcg will be combined with MF59C.1 and administered as one injection (0.5 mL) IM in either deltoid at baseline and Month 6. Participants in the study extension will receive an additional injection of the study vaccine approximately 14 to 20 months after their second (Month 6) vaccination.

No Previous HIV Vaccine Trial (Group 2); Previous HIV Vaccine Trial Participants (Group 1)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Access to a participating HVTN Clinical Research Site (CRS) and willing to be followed for the planned duration of the study
• Able and willing to provide informed consent
• Assessment of understanding: must demonstrate understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willing to receive HIV test results
• Willing 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 study clinic visit
• Assessed by the clinic staff as being at low risk for HIV infection
• Agrees not to enroll in another study of an investigational research agent prior to completion of last required study clinic visit
• In good general health as shown by medical history, physical exam, and screening laboratory tests
• For Group 1: Prior receipt of an HIV-1 subtype B envelope subunit vaccine (gp120, gp140) with MF59 adjuvant. More information on this criterion can be found in the protocol.
• Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell (WBC) count equal to 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
• Platelets equal to 125,000 to 550,000/mm\^3
• Chemistry panel: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 1.25 times the upper limit of normal; creatinine less than or equal to the institutional upper limits of normal

You may not qualify if:

• History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B within the 12 months prior to study entry
• Untreated or incompletely treated syphilis infection
• For Group 2 only: 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 088 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) or adjuvant(s) other than MF59 received within the 5 years prior to study entry in a prior vaccine trial. Exceptions may be made for vaccines/adjuvants that have subsequently undergone licensure by the FDA. For potential participants who have received an experimental vaccine(s)/adjuvant(s) greater than 5 years before study entry, eligibility for enrollment will be determined by the PSRT on a case-by-case basis. For potential participants who have received control/placebo in an experimental vaccine trial, the HVTN 088 PSRT will determine eligibility on a case-by-case basis.
• 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)
• Influenza vaccine or any vaccines that are not live attenuated vaccines (e.g., pneumococcal, tetanus, hepatitis A or B) and were received within 14 days prior to any vaccination
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• 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 \[length of therapy 10 days or less with completion at least 30 days prior to study entry\].)
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 60 days before 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 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 can be found in the protocol.
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, study adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Novartis Vaccines and Diagnostics, Inc: collaborator

Study Sites (3)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (2)

• Goepfert PA, Tomaras GD, Horton H, Montefiori D, Ferrari G, Deers M, Voss G, Koutsoukos M, Pedneault L, Vandepapeliere P, McElrath MJ, Spearman P, Fuchs JD, Koblin BA, Blattner WA, Frey S, Baden LR, Harro C, Evans T; NIAID HIV Vaccine Trials Network. Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers. Vaccine. 2007 Jan 5;25(3):510-8. doi: 10.1016/j.vaccine.2006.07.050. Epub 2006 Aug 10.

  PMID: 17049679 BACKGROUND

• Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, Ott RG, Anthony RM, Zebroski H, Hurley A, Phogat A, Chakrabarti B, Li Y, Connors M, Pereyra F, Walker BD, Wardemann H, Ho D, Wyatt RT, Mascola JR, Ravetch JV, Nussenzweig MC. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009 Apr 2;458(7238):636-40. doi: 10.1038/nature07930. Epub 2009 Mar 15.

  PMID: 19287373 BACKGROUND

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

• Paul Spearman

  Emory University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 20, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (3)