Evaluating the Safety of and Immune Response to the VSV-Indiana HIV Vaccine in Healthy, HIV-Uninfected Adults

NCT01438606 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 09011669
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and immune response to an HIV vaccine in HIV-uninfected adults. Study researchers will also determine the maximum dose of the vaccine that participants can safely receive.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (4)

• Change in frequency and severity of local injection site reactogenicity signs and symptoms

  Pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness; frequency and severity of systemic reactogenicity signs and symptoms: fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms

  Measured at Days 0, 1, 2, 4, 5, 6, 7, 60, 61, 62, 63, 64, 65, 66, and 67

• Frequency of adverse events (AEs) categorized by Medical Dictionary for Regulatory Activities (MedDRA) body system

  Frequency of AEs categorized by MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all serious adverse events (SAEs)

  Participants will be followed for the duration of the study, an expected average of 8 months

• Change in distribution of values of safety laboratory measures

  White blood cells (WBCs), neutrophils, lymphocytes, hemoglobin, alkaline phosphatase, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine at baseline and at follow-up visits postvaccination

  Measured at Days 3, 5, 9, and 140

• Number of participants with early discontinuation

  Number of participants with early discontinuation of vaccinations and reason for discontinuation

  Participants will be followed for the duration of the study, an expected average of 8 months

Secondary Outcomes (4)

• Change in response rates of CD4 T-cell responses

  Measured at Days 7, 14, 68, and 70

• Change in response rates of CD8 T-cell responses

  Measured at Days 7, 14, 68, and 70

• Change in response rates of T-cell responses

  Measured at Days 7, 14, 68, and 70

• Change in induction of binding antibodies to HIV-1 gag

  Measured at Days 7, 14, and 70

Study Arms (10)

1 x 10^4 PFU VSV-Indiana HIV gag vaccine (Group 1)

EXPERIMENTAL

Participants will receive 1 x 10\^4 PFU of the study vaccine by intramuscular (IM) injection in each deltoid at baseline and Week 8. (1 x 10\^4 PFU is the nominal dose; the actual dose is 4.6 x 10\^3 PFU given as 2.3 x 10\^3 PFU in each deltoid)

Biological: VSV-Indiana HIV gag vaccine

Placebo injection (normal saline) (Group 1)

PLACEBO COMPARATOR

Participants will receive placebo by IM injection in each deltoid at baseline and Week 8.

Biological: Placebo injection (normal saline)

1 x 10^5 PFU VSV-Indiana HIV gag vaccine (Group 2)

EXPERIMENTAL

Participants will receive 1 x 10\^5 PFU of the study vaccine by IM injection in each deltoid at baseline and Week 8. (1 x 10\^5 PFU is the nominal dose; the actual dose is 4.6 x 10\^4 PFU given as 2.3 x 10\^4 PFU in each deltoid)

Biological: VSV-Indiana HIV gag vaccine

Placebo injection (normal saline) (Group 2)

PLACEBO COMPARATOR

Participants will receive placebo by IM injection in each deltoid at baseline and Week 8.

Biological: Placebo injection (normal saline)

1 x 10^6 PFU VSV-Indiana HIV gag vaccine (Group 3)

EXPERIMENTAL

Participants will receive 1 x 10\^6 PFU of the study vaccine by IM injection in each deltoid at baseline and Week 8. (1 x 10\^6 PFU is the nominal dose; the actual dose is 4.8 x 10\^5 PFU given as 2.4 x 10\^5 PFU in each deltoid)

Biological: VSV-Indiana HIV gag vaccine

Placebo injection (normal saline) (Group 3)

PLACEBO COMPARATOR

Participants will receive placebo by IM injection in each deltoid at baseline and Week 8.

Biological: Placebo injection (normal saline)

1 x 10^7 PFU VSV-Indiana HIV gag vaccine (Group 4)

EXPERIMENTAL

Participants will receive 1 x 10\^7 PFU of the study vaccine by IM injection in each deltoid at baseline and Week 8. (1 x 10\^7 PFU is the nominal dose; the actual dose is 4.2 x 10\^6 PFU given as 2.1 x 10\^6 PFU in each deltoid)

Biological: VSV-Indiana HIV gag vaccine

Placebo injection (normal saline) (Group 4)

PLACEBO COMPARATOR

Participants will receive placebo by IM injection in each deltoid at baseline and Week 8.

Biological: Placebo injection (normal saline)

1 x 10^8 PFU VSV-Indiana HIV gag vaccine (Group 5)

EXPERIMENTAL

Participants will receive 1 x 10\^8 PFU of the study vaccine by IM injection in each deltoid at baseline and Week 8. (1 x 10\^8 PFU is the nominal dose; the actual dose is 3.4 x 10\^7 PFU given as 1.7 x 10\^7 PFU in each deltoid)

Biological: VSV-Indiana HIV gag vaccine

Placebo injection (normal saline) (Group 5)

PLACEBO COMPARATOR

Participants will receive placebo by IM injection in each deltoid at baseline and Week 8.

Biological: Placebo injection (normal saline)

Interventions

VSV-Indiana HIV gag vaccine BIOLOGICAL

Administered IM in both deltoids at baseline and Week 8. Dose will vary depending on which group the participant is enrolled in.

1 x 10^4 PFU VSV-Indiana HIV gag vaccine (Group 1); 1 x 10^5 PFU VSV-Indiana HIV gag vaccine (Group 2); 1 x 10^6 PFU VSV-Indiana HIV gag vaccine (Group 3); 1 x 10^7 PFU VSV-Indiana HIV gag vaccine (Group 4); 1 x 10^8 PFU VSV-Indiana HIV gag vaccine (Group 5)

Placebo injection (normal saline) BIOLOGICAL

Administered IM in both deltoids at baseline and Week 8.

Placebo injection (normal saline) (Group 1); Placebo injection (normal saline) (Group 2); Placebo injection (normal saline) (Group 3); Placebo injection (normal saline) (Group 4); Placebo injection (normal saline) (Group 5)

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 HVTN Clinical Research Site (CRS) and willing to be followed for the planned duration of the study
• Able and willing to provide informed consent
• Demonstrate understanding of this study by completing 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 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 study clinic visit (excludes annual contacts for safety surveillance)
• In 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, 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
• Platelets between 125,000 and 550,000/mm\^3
• Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and creatinine values less than or equal to institutional upper limits of normal

You may not qualify if:

• Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any other use of illicit drugs within the 6 months prior to study entry
• 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
• 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 090 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the 5 years prior to study entry 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 090 PSRT will determine eligibility on a case-by-case basis. For potential participants who have received an experimental vaccine(s) greater than 5 years prior to study entry, eligibility for enrollment will be determined by the 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 \[length of therapy 10 days or fewer with completion at least 30 days prior to study entry\].)
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 12 months 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)
• 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
• 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 090 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.

Sponsors & Collaborators

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

Study Sites (4)

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

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Rose NF, Marx PA, Luckay A, Nixon DF, Moretto WJ, Donahoe SM, Montefiori D, Roberts A, Buonocore L, Rose JK. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell. 2001 Sep 7;106(5):539-49. doi: 10.1016/s0092-8674(01)00482-2.

  PMID: 11551502 BACKGROUND

• Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, Lee W, Burwitz BJ, Stephany JJ, Loffredo JT, Allison DB, Adnan S, Hoji A, Wilson NA, Friedrich TC, Lifson JD, Yang OO, Watkins DI. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J Immunol. 2007 Mar 1;178(5):2746-54. doi: 10.4049/jimmunol.178.5.2746.

  PMID: 17312117 BACKGROUND

• Cooper D, Wright KJ, Calderon PC, Guo M, Nasar F, Johnson JE, Coleman JW, Lee M, Kotash C, Yurgelonis I, Natuk RJ, Hendry RM, Udem SA, Clarke DK. Attenuation of recombinant vesicular stomatitis virus-human immunodeficiency virus type 1 vaccine vectors by gene translocations and g gene truncation reduces neurovirulence and enhances immunogenicity in mice. J Virol. 2008 Jan;82(1):207-19. doi: 10.1128/JVI.01515-07. Epub 2007 Oct 17.

  PMID: 17942549 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Saline Solution

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)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jonathan Fuchs

  San Francisco Department of Public Health/University of California, San Francisco

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 19, 2011
• First Posted: September 22, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2013
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (4)