Evaluating the Safety and Immune Response to Three HIV Vaccine Schedules in Healthy, HIV-Uninfected Adults

NCT01783977 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 09211820
• Study Type: interventional
• Target: 143
• Locations: 2 countries
• Sites: 8

Brief Summary

NOTE: This study has stopped enrolling new participants, and all study vaccinations for currently enrolled participants have been stopped. Currently, there are no vaccines approved for the prevention of HIV infection, but there are many clinical trials taking place that are studying experimental HIV vaccines. The purpose of this study is to evaluate the safety and tolerability of three different HIV vaccine schedules in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (6)

• Local and systemic reactogenicity signs and symptoms

  Measured within the initial 7-day period following each vaccination visit

• Laboratory measures of safety

  Measured through participants' last study visit at approximately Day 224 to 334

• Adverse events (AEs)

  Measured through participants' last study visit at approximately Day 224 to 334

• Serious adverse events (SAEs)

  Measured through the end of participants' 5-year follow-up period

• HIV-specific CD4+ T cell magnitudes of responses 2 weeks after the NYVAC boost per arm, comparing Group 2 to Group 4 and Group 3 to Group 4

  Measured 2 weeks after participants receive the NYVAC vaccine boost

• HIV-specific CD8+ T cell magnitudes of responses 2 weeks after the NYVAC boost per arm, comparing Group 2 to Group 4 and Group 3 to Group 4

  Measured 2 weeks after participants receive the NYVAC vaccine boost

Secondary Outcomes (6)

• HIV-specific CD4+ T cell response rates and functional profiles 2 weeks after the NYVAC boost per arm

  Measured 2 weeks after participants receive the NYVAC vaccine boost

• HIV-specific CD8+ T cell response rates and functional profiles 2 weeks after the NYVAC boost per arm

  Measured 2 weeks after participants receive the NYVAC vaccine boost

• HIV-specific CD4+ T cell response rates, magnitudes of response, and functional profiles 2 weeks after the last DNA vaccination in Groups 2-4

  Measured 2 weeks after participants receive the last DNA vaccination

• HIV-specific CD8+ T cell response rates, magnitudes of response, and functional profiles 2 weeks after the last DNA vaccination in Groups 2-4

  Measured 2 weeks after participants receive the last DNA vaccination

• HIV-specific binding antibody responses 2 weeks after the NYVAC boost in Groups 2-4

  Measured 2 weeks after participants receive the NYVAC vaccine boost

Study Arms (7)

Part A: Group 1: Treatment

EXPERIMENTAL

Participants will receive the DNA-HIV-PT123 vaccine administered as 1 mL intramuscularly (IM) in the same deltoid at Days 0, 14, and 28.

Biological: DNA-HIV-PT123 vaccine

Part B: Group 2: Treatment

EXPERIMENTAL

Participants will receive the DNA-HIV-PT123 vaccine administered as 1 mL IM in the same deltoid at Days 0, 14, and 28. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the DNA-HIV-PT123 injection was given) at Day 84.

Biological: DNA-HIV-PT123 vaccine; Biological: NYVAC-HIV-PT1 vaccine; Biological: NYVAC-HIV-PT4 vaccine

Part B: Group 2: Placebo

PLACEBO COMPARATOR

Participants will receive the placebo vaccine for DNA-HIV-PT123 administered as 1 mL IM in the same deltoid at Days 0, 14, and 28. They will then receive the placebo vaccine for NYVAC-HIV-PT1 and the placebo vaccine for NYVAC-HIV-PT4; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the placebo for DNA-HIV-PT123 injection was given) at Day 84.

Biological: Placebo for DNA-HIV-PT123 vaccine; Biological: Placebo for NYVAC-HIV-PT1 vaccine; Biological: Placebo for NYVAC-HIV-PT4 vaccine

Part B: Group 3: Treatment

EXPERIMENTAL

Participants will receive the DNA-HIV-PT123 vaccine administered as 1 mL IM in the same deltoid at Days 0 and 28. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the DNA-HIV-PT123 injection was given) at Day 84.

Biological: DNA-HIV-PT123 vaccine; Biological: NYVAC-HIV-PT1 vaccine; Biological: NYVAC-HIV-PT4 vaccine

Part B: Group 3: Placebo

PLACEBO COMPARATOR

Participants will receive the placebo vaccine for DNA-HIV-PT123 administered as 1 mL IM in the same deltoid at Days 0 and 28. They will then receive the placebo vaccine for NYVAC-HIV-PT1 and the placebo vaccine for NYVAC-HIV-PT4; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the placebo for DNA-HIV-PT123 injection was given) at Day 84.

Biological: Placebo for DNA-HIV-PT123 vaccine; Biological: Placebo for NYVAC-HIV-PT1 vaccine; Biological: Placebo for NYVAC-HIV-PT4 vaccine

Part B: Group 4: Treatment

EXPERIMENTAL

Participants will receive the DNA-HIV-PT123 vaccine administered as 1 mL IM in the same deltoid at Days 0, 28, and 56. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the DNA-HIV-PT123 injection was given) at Day 140.

Biological: DNA-HIV-PT123 vaccine; Biological: NYVAC-HIV-PT1 vaccine; Biological: NYVAC-HIV-PT4 vaccine

Part B: Group 4: Placebo

PLACEBO COMPARATOR

Participants will receive the placebo vaccine for DNA-HIV-PT123 administered as 1 mL IM in the same deltoid at Days 0, 28, and 56. They will then receive the placebo vaccine for NYVAC-HIV-PT1 and the placebo vaccine for NYVAC-HIV-PT4; each will be administered as 1 mL IM in the same deltoid (opposite deltoid to where the placebo for DNA-HIV-PT123 injection was given) at Day 140.

Biological: Placebo for DNA-HIV-PT123 vaccine; Biological: Placebo for NYVAC-HIV-PT1 vaccine; Biological: Placebo for NYVAC-HIV-PT4 vaccine

Interventions

DNA-HIV-PT123 vaccine BIOLOGICAL

DNA-HIV-PT123 4 mg/mL; administered as 1 mL IM in participant's deltoid

Part A: Group 1: Treatment; Part B: Group 2: Treatment; Part B: Group 3: Treatment; Part B: Group 4: Treatment

NYVAC-HIV-PT1 vaccine BIOLOGICAL

NYVAC-HIV-PT1 at greater than or equal to 5x10\^6 plaque-forming units (PFU)/ml for a planned maximum dose of 1.2x10\^8 PFU/ml; administered as 1 mL IM in participant's deltoid

Part B: Group 2: Treatment; Part B: Group 3: Treatment; Part B: Group 4: Treatment

NYVAC-HIV-PT4 vaccine BIOLOGICAL

NYVAC-HIV-PT4 at greater than or equal to 5x10\^6 PFU/ml for a planned maximum dose of 1.1x10\^7 PFU/ml; administered as 1 mL IM in participant's deltoid

Part B: Group 2: Treatment; Part B: Group 3: Treatment; Part B: Group 4: Treatment

Placebo for DNA-HIV-PT123 vaccine BIOLOGICAL

Placebo for DNA-HIV-PT123 administered as 1 mL IM in participant's deltoid

Part B: Group 2: Placebo; Part B: Group 3: Placebo; Part B: Group 4: Placebo

Placebo for NYVAC-HIV-PT1 vaccine BIOLOGICAL

Placebo for NYVAC-HIV-PT1 vaccine administered as 1 mL IM in participant's deltoid

Part B: Group 2: Placebo; Part B: Group 3: Placebo; Part B: Group 4: Placebo

Placebo for NYVAC-HIV-PT4 vaccine BIOLOGICAL

Placebo for NYVAC-HIV-PT4 vaccine administered as 1 mL IM in the participant's deltoid

Part B: Group 2: Placebo; Part B: Group 3: Placebo; Part B: Group 4: Placebo

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 willing 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
• 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 5 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
• 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 and greater than or equal to 13.0 g/dL for participants 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), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal (IULN); creatinine less than 1.1 times the IULN

You may not qualify if:

• Untreated or incompletely treated syphilis infection
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 092 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 volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 092 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 092 PSRT on a case-by-case basis.
• 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.)
• 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 before the last required protocol clinic visit
• 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 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, 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. (Not excluded: participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)

Sponsors & Collaborators

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

Study Sites (8)

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

UIC Project WISH CRS

Chicago, Illinois, 60612, United States

Location

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

Boston, Massachusetts, 02115-6110, United States

Location

Penn Prevention Crs

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Lausanne Vaccine and Immunotherapy Center CRS

Lausanne, Canton of Vaud, 1011, Switzerland

Location

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

  CHUV

  STUDY CHAIR

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: February 1, 2013
• First Posted: February 5, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: October 24, 2018
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (7); CH (1)