Evaluating the Safety and Immune Response to Five Different Combinations of HIV Vaccines in Healthy, HIV-Uninfected Adults

NCT01964937 | Withdrawn Phase 1 DMC

• 2 other identifiers: HVTN 10211937
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety and immune response to five different combinations of three HIV vaccines in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (5)

• Local and systemic reactogenicity signs and symptoms

  Measured up to 7 days post the last vaccination

• Laboratory measures of safety

  Measured through participants' last study visit at Month 12

• Adverse events (AEs) and serious adverse events (SAEs)

  Measured through last annual health contact at Month 36

• HIV-specific binding antibody (Ab) response as assessed by binding Ab multiplex assay

  Measured 2 weeks after the 4th vaccination (Month 6)

• Response rate and magnitude of CD4 and CD8 T-cell responses as assessed by intracellular cytokine staining (ICS) assays

  Measured 2 weeks after the 4th vaccination (Month 6)

Secondary Outcomes (3)

• HIV-specific binding Ab and T-cell responses

  Measured 2 weeks after the 4th vaccination (Month 6)

• Neutralizing antibody (nAb) magnitude and breadth against tier 1 and tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves

  Measured 2 weeks after the 4th vaccination (Month 6)

• HIV-specific Ab and T-cell responses

  Measured 6 months after the 4th vaccination (Month 12)

Study Arms (5)

Group 1

EXPERIMENTAL

At Months 0 and 1, participants in Group 1 will receive one injection of AIDSVAX B/E ® administered intramuscularly (IM) in the right deltoid and two injections of placebo vaccine administered IM in the left deltoid. At Months 3 and 6, participants will receive two injections of NYVAC vaccine (NYVAC-HIV-PT1 and NYVAC-HIV-PT4) administered IM in the left deltoid and one injection of placebo vaccine administered IM in the right deltoid.

Biological: NYVAC-HIV-PT1; Biological: NYVAC-HIV-PT4; Biological: AIDSVAX B/E®

Group 2

EXPERIMENTAL

At Months 0 and 1, participants in Group 2 will receive two injections of NYVAC vaccine (NYVAC-HIV-PT1 and NYVAC-HIV-PT4) administered IM in the left deltoid and one injection of placebo vaccine administered IM in the right deltoid. At Months 3 and 6, participants will receive the AIDSVAX ® B/E vaccine administered IM in the right deltoid and two injections of placebo vaccine administered IM in the left deltoid.

Biological: NYVAC-HIV-PT1; Biological: NYVAC-HIV-PT4; Biological: AIDSVAX B/E®

Group 3

EXPERIMENTAL

At Months 0 and 1, participants in Group 3 will one injection of the AIDSVAX B/E vaccine administered IM in the right deltoid and one injection of placebo vaccine administered IM the left deltoid. At Months 3 and 6, participants will receive one injection of the DNA-HIV-PT123 vaccine administered IM in the left deltoid and one injection of placebo vaccine administered IM in the right deltoid.

Biological: DNA-HIV-PT123; Biological: AIDSVAX B/E®; Biological: Placebo vaccine

Group 4

EXPERIMENTAL

At Months 0 and 1, participants in Group 4 will receive one injection of the DNA-HIV-PT123 vaccine administered IM in the left deltoid and one injection of placebo vaccine administered IM in the right deltoid. At Months 3 and 6, participants will receive one injection of the AIDSVAX B/E ® vaccine administered IM in the right deltoid and one injection of placebo vaccine administered IM the left deltoid.

Biological: DNA-HIV-PT123; Biological: AIDSVAX B/E®; Biological: Placebo vaccine

Group 5

EXPERIMENTAL

At Months 0, 1, 3, and 6, participants in Group 5 will receive one injection of the DNA-HIV-PT123 vaccine administered in the left deltoid and one injection of the AIDSVAX B/E ® vaccine administered IM in the right deltoid.

Biological: DNA-HIV-PT123; Biological: AIDSVAX B/E®

Interventions

DNA-HIV-PT123 BIOLOGICAL

The DNA-HIV-PT123 (containing clade C ZM96 gag and gp140 along with CN54 pol-nef) will be administered at a dose of 4 mg IM.

Group 3; Group 4; Group 5

NYVAC-HIV-PT1 BIOLOGICAL

The NYVAC-HIV-PT1 vaccine (containing clade C ZM96 gp140) will be administered at a dose of greater than or equal to 5×10\^6 plaque-forming units (PFU)IM, for a planned maximum dose of 1.2×10\^8 PFU.

Group 1; Group 2

NYVAC-HIV-PT4 BIOLOGICAL

The NYVAC-HIV-PT4 vaccine (containing ZM96 gag-CN54 pol-nef) will be administered at a dose of greater than or equal to 5×10\^6 PFU IM, for a planned maximum dose of 1.1×10\^7 PFU.

Group 1; Group 2

AIDSVAX B/E® BIOLOGICAL

The AIDSVAX B/E ® vaccine will be administered as a 1 mL/600 mcg dose IM.

Group 1; Group 2; Group 3; Group 4; Group 5

Placebo vaccine BIOLOGICAL

The placebo vaccine contains sodium chloride for injection USP, 0.9% and will be administered as a 1 mL injection IM.

Group 3; Group 4

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; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• 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 before the last required protocol clinic visit
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• 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
• Assessed by the clinic staff as being at "low risk" for HIV infection
• 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 volunteers who were born male
• White blood cell 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) less than 1.25 times the institutional upper limit of normal (IULN) and creatinine less than or equal to IULN.

You may not qualify if:

• 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; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45 years, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or known hyperlipidemia
• Intent to participate in another study of an investigational research agent before the last required protocol clinic visit
• Pregnant or breastfeeding
• HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 102 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 participants who have received control/placebo in an experimental vaccine trial, the HVTN 102 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 102 PSRT 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 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
• Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment.
• Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child)
• Immunoglobulin received within 60 days before first vaccination
• Autoimmune disease (Not excluded: mild, well-controlled psoriasis)
• Immunodeficiency

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• IPPOX Foundation: collaborator
• EuroVacc Foundation: collaborator
• Global Solutions for Infectious Diseases: collaborator

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX B-E

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

• Michael Keefer

  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: October 15, 2013
• First Posted: October 17, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 15, 2021

Record last verified: 2021-10