Evaluating the Immunogenicity of the AIDSVAX B/E Vaccine and the MVA/HIV62B Vaccine in Healthy, HIV-1-Uninfected Adults Who Previously Received MVA/HIV62B in DNA/MVA or MVA/MVA Regimens in HVTN 205

NCT02852005 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 11412035
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of the AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens in the HVTN 205 study.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (16)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Left Arm (MVA/HIV62B or Placebo)

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after the boost at Month 0 and Month 4

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms of the Right Arm (AIDSVAX B/E or Placebo)

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after the boost at Month 0 and Month 4

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Boost Regimen

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\], The maximum grade observed for each symptom over the time frame is presented.

  Measured through Month Measured through 3 days after each boost at Month 0 and 4

• Number of Participants With Early Study Termination Associated With an AE or Reactogenicity

  From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm

  Measured through Month 10

• Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

  Measured through the Month 4 boost

• Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L

  For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  Measured during screening, and 2 weeks after each boost at Month 0 and 4

• Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL

  For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  Measured during screening, and 2 weeks after each boost at Month 0 and 4

• Chemistry and Hematology Laboratory Measures, for Each Boost: WBC, Platelets, Lymphocytes, Neutrophils

  For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  Measured during screening, and 2 weeks after each boost at Month 0 and 4

• Occurrence of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.

  Measured at Month 0.5 and 4.5

• Level of Env-specific IgG Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.

  Measured at Month 0.5 and 4.5

• Occurrence of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.

  Measured at Month 0.5 and 4.5

• Level of Env-specific IgG3 Responses for gp120, gp41, V1/V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. The responses to the IDR of gp41 was not assayed.

  Measured at Month 0.5 and 4.5

• Occurrence of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. IgA responses to V1V2 and the IDR of gp41 were not assayed.

  Measured at Month 0.5 and 4.5

• Level of Env-specific IgA Responses for gp120, gp41, V1V2, and the IDR of gp41 at 2 Weeks After Each Boost

  Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. IgA responses to V1V2 and the IDR of gp41 were not assayed.

  Measured at Month 0.5 and 4.5

• Occurrence of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost

  Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay measured neutralization titers against a panel of autologous and heterologous Env-pseudotyped viruses.

  Measured at Month 0.5 and 4.5

• Level of Neutralizing Ab Titers and Breadth Against the Env Vaccine Strain and Heterologous Tier 1 Strains at 2 Weeks After Each Boost

  Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay measured neutralization titers against a panel of autologous and heterologous Env-pseudotyped viruses. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% (ID50) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). Titer \< 10 is truncated at 5.

  Measured at Month 0.5 and 4.5

Secondary Outcomes (6)

• Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost

  Measured at Month 4.5

• Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost

  Measured at Month 4.5

• Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost

  Measured at Month 4.5

• Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine 2 Weeks After Each Boost

  Measured at Month 4.5

• Occurrence of Env-specific IgG Responses for gp120, gp140, V1/V2, and the IDR of gp41 at 6 Months After the Final Boost

  Measured at Month 10

Study Arms (5)

Group 1: MVA/HIV62B + Placebo

EXPERIMENTAL

Participants who received 3 sequential administrations of MVA/HIV62B in HVTN 205 will receive the MVA/HIV62B vaccine in their left deltoid at Months 0 and 4. They will receive placebo in their right deltoid at Months 0 and 4.

Biological: MVA/HIV62B vaccine; Biological: Placebo

Group 2: MVA/HIV62B + AIDSVAX B/E

EXPERIMENTAL

Participants who received 3 sequential administrations of MVA/HIV62B in HVTN 205 will receive the MVA/HIV62B vaccine in their left deltoid at Months 0 and 4. They will receive the AIDSVAX B/E vaccine in their right deltoid at Months 0 and 4.

Biological: MVA/HIV62B vaccine; Biological: AIDSVAX B/E vaccine

Group 3: MVA/HIV62B + Placebo

EXPERIMENTAL

Participants who received 2 sequential priming administrations of JS7 DNA plasmid followed by 2 sequential boost administrations of MVA/HIV62B in HVTN 205 will receive the MVA/HIV62B vaccine in their left deltoid at Months 0 and 4. They will receive placebo in their right deltoid at Months 0 and 4.

Biological: MVA/HIV62B vaccine; Biological: Placebo

Group 4: MVA/HIV62B + AIDSVAX B/E

EXPERIMENTAL

Participants who received 2 sequential priming administrations of JS7 DNA plasmid followed by 2 sequential boost administrations of MVA/HIV62B in HVTN 205 will receive the MVA/HIV62B vaccine in their left deltoid at Months 0 and 4. They will receive the AIDSVAX B/E vaccine in their right deltoid at Months 0 and 4.

Biological: MVA/HIV62B vaccine; Biological: AIDSVAX B/E vaccine

Group 5: Placebo + AIDSVAX B/E

EXPERIMENTAL

Participants who received 2 sequential priming administrations of JS7 DNA plasmid followed by 2 sequential boost administrations of MVA/HIV62B in HVTN 205 will receive placebo in their left deltoid at Months 0 and 4. They will receive the AIDSVAX B/E vaccine in their right deltoid at Months 0 and 4.

Biological: AIDSVAX B/E vaccine; Biological: Placebo

Interventions

MVA/HIV62B vaccine BIOLOGICAL

1×10\^8 TCID50 dose to be administered as a 1 mL intramuscular (IM) injection in the deltoid

Group 1: MVA/HIV62B + Placebo; Group 2: MVA/HIV62B + AIDSVAX B/E; Group 3: MVA/HIV62B + Placebo; Group 4: MVA/HIV62B + AIDSVAX B/E

AIDSVAX B/E vaccine BIOLOGICAL

600 mcg/mL dose to be administered as a 1 mL IM injection in the deltoid

Group 2: MVA/HIV62B + AIDSVAX B/E; Group 4: MVA/HIV62B + AIDSVAX B/E; Group 5: Placebo + AIDSVAX B/E

Placebo BIOLOGICAL

Sodium Chloride for Injection USP, 0.9% to be administered as a 1 mL IM injection in the deltoid

Group 1: MVA/HIV62B + Placebo; Group 3: MVA/HIV62B + Placebo; Group 5: Placebo + AIDSVAX B/E

Eligibility Criteria

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

You may qualify if:

• General and Demographic Criteria:
• Age of 18 to 55 years
• Prior participation in HVTN 205 with assignment to treatment (not placebo) arm:
• Assigned to HVTN 205 Group 1 or Group 3, and received all 4 scheduled vaccinations (2 injections of pGA2/JS7 DNA (months 0, 2) and 2 injections of MVA/HIV62 (months 4, 6); OR
• Assigned to HVTN 205 Group 4, and received at least vaccinations 1, 2 and 4 (3 injections of MVA/HIV62 at months 0, 2 and 6).
• Access to a participating 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: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willing to be contacted 2 years following initial study injection.
• Agrees not to enroll in another study of an investigational research agent
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria:
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.

You may not qualify if:

• General
• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) greater than or equal to 40
• Volunteer has 2 or more of the following cardiac risk factors:
• Participant report of history of elevated blood cholesterol defined as fasting LDL greater than 160 mg/dL;
• First degree relative (eg, mother, father, brother, or sister) who had coronary artery disease before the age of 50 years;
• Current smoker; or
• BMI greater than or equal to 35
• Pregnant or breastfeeding
• Active duty and reserve U.S. military personnel
• Vaccines and Other Injections
• Any clinically significant AE related to vaccination in HVTN 205, for which revaccination would be a safety concern such as any grade 3 or 4 related AE
• Smallpox vaccine received within the last 5 years
• HIV vaccine(s) received in a prior HIV vaccine trial other than HVTN 205. For HVTN 205 participants who have subsequently received control/placebo in another HIV vaccine trial, the HVTN 114 PSRT will determine eligibility on a case-by-case basis.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (9)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

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

Boston, Massachusetts, 02115-6110, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

ACSA CRS

Iquitos, Maynas, 1, Peru

Location

Barranco CRS

Lima, 04 - 15063, Peru

Location

Related Publications (2)

• Huang Y, Seaton KE, Casapia M, Polakowski L, De Rosa SC, Cohen K, Yu C, Elizaga M, Paez C, Miner MD, Kelley CF, Maenza J, Keefer M, Lama JR, Sobieszczyk M, Buchbinder S, Baden LR, Lee C, Gulati V, Sinangil F, Montefiori D, McElrath MJ, Tomaras GD, Robinson HL, Goepfert P; NIAID-funded HIV Vaccine Trials Network (HVTN) 114 Study Team. AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period. Vaccine. 2021 Jul 30;39(33):4641-4650. doi: 10.1016/j.vaccine.2021.06.066. Epub 2021 Jul 3.

  PMID: 34229888 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

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Paul Goepfert

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 2, 2016
• Study Start: January 1, 2017
• Primary Completion: August 29, 2018
• Study Completion: October 29, 2019
• Last Updated: August 8, 2022
• Results First Posted: April 1, 2021

Record last verified: 2022-08

Locations

PE (2); US (7)