Phase 1 Safety Study of Two Experimental HIV Vaccines

NCT00479999 | Completed Phase 1

• 2 other identifiers: 07016707-I-0167
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether two experimental HIV vaccines are safe and whether they cause any side effects in healthy adults. It will examine the body s immune response to the vaccines and monitor the social impact, if any, of being in an HIV vaccine study. The experimental vaccines in this study are the VRC-HIVADV027-00-VP (also called the rAd35-EnvA vaccine) and VRC-HIVADV038-00-VP (also called the rAd5-EnvA vaccine). The vaccines are made using an adenovirus (virus that normally causes respiratory infections and colds) that has been modified to contain DNA that codes for HIV proteins. The vaccines cannot cause HIV or adenoviral infections. Healthy normal volunteers between 18 and 50 years of age may be eligible for this 2-part study. Part 1 includes 15 people. Part 2 includes 20 people. Part 1 participants receive only the rAd35-EnvA vaccine. The first five people enrolled receive the lowest study dose of the vaccine. If this dose is safe, then the next five people enrolled receive a higher dose. If this dose is safe, then the last 5 people enrolled receive the highest study dose. Subjects in Part I have about five clinic visits over 24 weeks. Part II of the study starts after all injections in Part 1 are given. Subjects in Part 2 are randomly assigned to one of two vaccination schedules. One group receives the rAd35-EnvA vaccine first, followed 12 weeks later with the rAd5-EnvA vaccine. The other group receives the vaccines in reverse order; that is, first the rAd5-EnvA vaccine, followed 12 weeks later with the rAd35-EnvA vaccine. In this schedule, the first vaccination primes the immune system and then the immune response is boosted 12 weeks later with a different vaccine. Everyone in study Part 2 receives the rAd35-EnvA vaccine at the middle dose tested in Part 1. Subjects in Part 2 have about eight clinic visits over 36 weeks. All vaccinations are given as injections in the upper arm. At each clinic visit, participants are checked for health changes or problems. They are asked how they are feeling and if they have taken any medications. Urine samples are collected and blood is drawn at some visits. They are tested for HIV several times and asked questions about their sexual behavior and drug use. Throughout the study, participants are counseled on HIV risk reduction. Subjects are asked about any social effects they may have experienced from their participation in this study.

Conditions

AIDS Vaccines; HIV Infections; HIV-1

Keywords

HIV-Negative; Healthy; Immunity; Preventive; Virus; Healthy Volunteer; HV; HIV Preventive Vaccine

Outcome Measures

Primary Outcomes (1)

• Safety (local and systemic reactogenicity, lab tests, AEs)

Secondary Outcomes (1)

• Immunogenicity (cellular and humoral immune function assays)

Interventions

VRC-HIVADV027-00-VP DRUG

VRC-HIVADV038-00-VP DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A participant must meet all of the following criteria:
• to 50 years old.
• Available for clinical follow-up through Week 24 of the study for subjects in Part I: available for clinical follow-up through Week 52 for subjects in Part II and committed to 4 years of annual follow-up contact after Week 52 if in Part II of the study.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Complete an Assessment of Understanding (that includes understanding of Step Study results) prior to enrollment and verbalize understanding of all questions answered incorrectly.
• Able and willing to complete the informed consent process.
• Willing to receive HIV test results and willing to abide by NIH guidelines for partner notification of positive HIV results.
• Willing to donate blood for sample storage to be used for future research.
• Willing to discuss HIV infection risks, amenable to risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit and assessed by the clinic staff as being at low risk of HIV infection on the basis of behaviors in the 12 months prior to enrollment as follows:
• Sexually abstinent
• Had two or fewer mutually monogamous relationships with partners believed to be HIV-uninfected and who did not use injection drugs, crack cocaine or methamphetamine
• Had three or fewer partners believed to be HIV-uninfected and who did not use injection drugs, crack cocaine or methamphetamine and with whom he/she regularly used condoms for vaginal or anal intercourse.
• In good general health without clinically significant medical history.
• Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment.
• Laboratory Criteria within 56 days prior to enrollment:

You may not qualify if:

• A volunteer will be excluded if one or more of the following conditions apply:
• Women:
• Woman who is breast-feeding or planning to become pregnant during the 12 weeks of study participation for subjects in Part I and 24 weeks of study participation for subjects in Part II.
• Volunteer has received any of the following substances:
• HIV vaccine in a prior clinical trial.
• Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past three months. \[With the exceptions that use of corticosteroid nasal spray for rhinitis; topical corticosteroids for an acute uncomplicated dermatitis; short-acting beta-agonists in controlled asthmatics; or a short course (10 days or less) of corticosteroids for a non-chronic condition at least 2 weeks prior to enrollment in this study will not exclude study participation.\]
• Blood products within 120 days prior to HIV screening.
• Immunoglobulin within 60 days prior to HIV screening.
• Investigational research agents within 30 days prior to initial study vaccine administration.
• Live attenuated vaccines within 30 days prior to initial study vaccine administration.
• Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration.
• Current anti-tuberculosis prophylaxis or therapy.
• Volunteer has a history of any of the following clinically significant conditions:
• Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
• Idiopathic urticaria within the past 2 years.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.

  PMID: 15761255 BACKGROUND

• Casimiro DR, Chen L, Fu TM, Evans RK, Caulfield MJ, Davies ME, Tang A, Chen M, Huang L, Harris V, Freed DC, Wilson KA, Dubey S, Zhu DM, Nawrocki D, Mach H, Troutman R, Isopi L, Williams D, Hurni W, Xu Z, Smith JG, Wang S, Liu X, Guan L, Long R, Trigona W, Heidecker GJ, Perry HC, Persaud N, Toner TJ, Su Q, Liang X, Youil R, Chastain M, Bett AJ, Volkin DB, Emini EA, Shiver JW. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. J Virol. 2003 Jun;77(11):6305-13. doi: 10.1128/jvi.77.11.6305-6313.2003.

  PMID: 12743287 BACKGROUND

• Letvin NL, Huang Y, Chakrabarti BK, Xu L, Seaman MS, Beaudry K, Korioth-Schmitz B, Yu F, Rohne D, Martin KL, Miura A, Kong WP, Yang ZY, Gelman RS, Golubeva OG, Montefiori DC, Mascola JR, Nabel GJ. Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys. J Virol. 2004 Jul;78(14):7490-7. doi: 10.1128/JVI.78.14.7490-7497.2004.

  PMID: 15220422 BACKGROUND

• Crank MC, Wilson EM, Novik L, Enama ME, Hendel CS, Gu W, Nason MC, Bailer RT, Nabel GJ, McDermott AB, Mascola JR, Koup RA, Ledgerwood JE, Graham BS; VRC012 Study Team. Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012). PLoS One. 2016 Nov 15;11(11):e0166393. doi: 10.1371/journal.pone.0166393. eCollection 2016.

  PMID: 27846256 DERIVED

MeSH Terms

Conditions

HIV Infections; Virus Diseases

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Barney S Graham, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 26, 2007
• First Posted: May 30, 2007
• Study Start: May 24, 2007
• Primary Completion: May 5, 2014
• Study Completion: May 5, 2014
• Last Updated: December 16, 2019

Record last verified: 2014-05-05

Locations

US (1)