Safety of and Immune Response to an HIV-1 Vaccine (VRC-HIVDNA016-00-VP) and a Vaccine Booster (VRC-HIVADV014-00-VP) in HIV Uninfected East African Adults

A Phase I/II Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1 DNA Plasmid Vaccine, VRC-HIVDNA016-00-VP, Boosted by a Multiclade HIV-1 Recombinant Adenovirus-5 Vector Vaccine, VRC-HIVADV014-00-VP, in HIV Uninfected Adult Volunteers in East Africa

The purpose of the study is to determine the safety of and immune response to an investigational HIV vaccine, VRC-HIVDNA016-00-VP, and a vaccine booster, VRC-HIVADV014-00-VP, in HIV uninfected adults from Kenya, Tanzania, and Uganda.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: VRC-HIVDNA016-00-VP; Biological: VRC-DILUENT013-DIL-VP; Biological: VRC-HIVADV014-00-VP; Biological: VRC-HIVADV014-00-VP placebo

Detailed Description

The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. This study will evaluate the safety and immunogenicity of an experimental adenovirus-vectored multiclade HIV vaccine, VRC-HIVADV014-00-VP, followed with or without a similarly structured DNA plasmid HIV vaccine, VRC-HIVDNA016-00-VP. The DNA in both vaccines codes for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. HIV uninfected volunteers will be recruited in the East African nations of Kenya, Tanzania, and Uganda.

This study will comprise two parts, 1 and 2. Part 1 will enroll 144 participants who will be randomly assigned to one of four different groups:

• Group 1A participants will receive a low dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
• Group 1B participants will receive a higher dose of the adenovirus-vectored HIV vaccine or placebo at study entry.
• Group 1C will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.
• Group 1D will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a higher dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.

Enrollment into Part 2 (Groups 2A and 2B) will begin after the completion of the safety data evaluation of Groups 3 and 4 and after Part A has been fully enrolled. Group 2A participants will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.

There will be 11 study visits over 14 to 16 months for Parts 1 and 2. All study visits will include a physical exam, medical and medication history, vital signs measurement, lymph node assessment, HIV and pregnancy counseling, and blood and urine collection. A home visit will also occur at study entry. A 3-day diary card to report side effects will be completed by participants at study entry and on Days 28, 56, 168, and 210.

There will be 14 study visits for Groups 3, 4, and 5; these visits will include the same tests and assessments as for Groups 1 and 2.

As per an amendment (dated December 19, 2005), follow-up for this study will be extended. The purpose for this extension is to examine in greater depth the efficacy of the vaccine. Specifically, investigators will be exploring whether there is a persistent immune response in participants who received the vaccine as well as if new or boosted responses to the adenovirus vaccine are persistent. The extended follow-up will last for 2 years with clinic visits every 4 months. During visits blood will be drawn for laboratory tests, including HIV testing. Participants will also be informed of ways to reduce their risk of contracting HIV. Two weeks after each visit, participants will be asked to come to the study site for a short post HIV test counseling visit. There will be a total of 6 visits per year, 3 follow-up visits, and 3 post HIV test counseling visits. There will be no more vaccinations.

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Kenya
  • Kericho, Kenya, 20200
    • Kenya Med. Research Inst./Walter Reed Project, Clinical Research Centre, Off Hospital Road. Kericho
• Tanzania
  • Mbeya, Tanzania, 025
    • National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) CRS
• Uganda
  • Kampala, Uganda
    • Makerere University Walter Reed Project (MUWRP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Good general health
• Willing to follow all the requirements of the study and available for follow-up for the duration of the study (14 to 16 months)
• Able and willing to provide informed consent
• Willing to undergo HIV testing and counseling and willing to receive HIV test results
• Willing to not engage in high-risk behavior for HIV infection during the study
• Willing to provide location and be visited at home
• Willing to be identified with picture identification for study purposes
• Willing to use acceptable forms of contraception
• Pregnant women and those with conditions which render phlebotomy volumes hazardous will be allowed to participate using a minimized phlebotomy schedule

Exclusion Criteria:

• HIV or HBV infection
• HIV vaccines in prior HIV vaccine trial
• Immunosuppressive or cytotoxic medications within the 6 months prior to study entry. Participants who have used corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for acute uncomplicated dermatitis are not excluded.
• Blood products within 120 days prior to study entry
• Immunoglobulin within 60 days prior to study entry
• Live attenuated vaccines within 30 days prior to first study vaccine administration
• Medically indicated subunit or killed vaccines or allergy treatment with antigen injections within 14 days prior to first study vaccine administration
• Investigational research agents within 30 days prior to first study vaccine administration
• Current tuberculosis prophylaxis or therapy
• Participated in high-risk behavior for HIV infection within 6 months prior to study entry. More information on this criterion can be found in the protocol.
• Serious adverse reactions to vaccines, such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain
• Autoimmune disease or immunodeficiency
• Unstable asthma or asthma requiring emergent or urgent care, hospitalization, intubation, or oral or intravenous corticosteroids during the 2 years prior to study entry
• Diabetes mellitus type 1 or 2. Patients with gestational diabetes are not excluded.
• Thyroid disease, including removal of thyroid or disease requiring medication within 3 years prior to study entry
• Serious angioedema within 3 years prior to study entry or disease requiring medication within 2 years prior to study entry
• Uncontrolled hypertension
• Bleeding disorder
• Active syphilis
• Active cancer OR treated cancer that may recur during the duration of the study
• Seizure disorder. Participants who have had fever-related seizures prior to age 2 are not excluded.
• Absence of spleen OR partial or complete lack of splenic function
• Psychiatric condition that may interfere with the study, including past or present psychoses, bipolar disorder, or suicidal attempts
• Any medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with the study
• Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
• Pregnancy, breastfeeding, or plan to become pregnant
• Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
• Incapacitating illness precluding clinic visits
• Unable to provide informed consent
• Prisoners will not be enrolled while incarcerated and if enrolled prior to incarceration, will not be followed while in confinement. Re-consent will not be required upon release from prison.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1A; Participants will receive a low dose of the adenovirus-vectored HIV vaccine or placebo at study entry	Biological: VRC-HIVDNA016-00-VP; 1x10^11 per unit vaccine administered intramuscularly via Bioinjector; Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo
Experimental: 1B; Participants will receive a higher dose of the adenovirus-vectored HIV vaccine or placebo at study entry	Biological: VRC-HIVDNA016-00-VP; 1x10^11 per unit vaccine administered intramuscularly via Bioinjector; Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo
Experimental: 1C; Participants will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a low dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.	Biological: VRC-HIVDNA016-00-VP; 1x10^11 per unit vaccine administered intramuscularly via Bioinjector; Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo; Biological: VRC-HIVADV014-00-VP; 4 mg administered intramuscularly via injection; Biological: VRC-HIVADV014-00-VP placebo; 4 mg administered intramuscularly via injection
Experimental: 1D; Participants will receive the DNA plasmid vaccine or placebo at study entry and Days 28 and 56. They will also receive either a higher dose of the adenovirus-vectored HIV vaccine or placebo at Day 168.	Biological: VRC-HIVDNA016-00-VP; 1x10^11 per unit vaccine administered intramuscularly via Bioinjector; Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo; Biological: VRC-HIVADV014-00-VP; 4 mg administered intramuscularly via injection; Biological: VRC-HIVADV014-00-VP placebo; 4 mg administered intramuscularly via injection
Experimental: 2A; Participants will receive the DNA plasmid vaccine at study entry and Days 28 and 56. They will also receive a low dose of the adenovirus-vectored HIV vaccine at Day 168.	Biological: VRC-HIVDNA016-00-VP; 1x10^11 per unit vaccine administered intramuscularly via Bioinjector; Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo; Biological: VRC-HIVADV014-00-VP; 4 mg administered intramuscularly via injection
Experimental: 2B; Participants will receive the DNA plasmid vaccine placebo at study entry and Days 28 and 56. They will also receive a the adenovirus-vectored HIV vaccine placebo at Day 168.	Biological: VRC-DILUENT013-DIL-VP; Administered intramuscularly via Bioinjector; Other Names: VRC-HIVDNA016-00-VP placebo; Biological: VRC-HIVADV014-00-VP placebo; 4 mg administered intramuscularly via injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local reactogenicity signs and symptoms	Throughout study
Systemic reactogenicity signs and symptoms	Throughout study
Laboratory measures of safety	Throughout study
Adverse and serious adverse experiences	Throughout study
Unfractionated IFN-gamma ELISPOT responses to HIV-1	At Day 196
CD4+ and CD8+ T cell responses to HIV-1, as measured by flow cytometry-based intracellular cytokine staining (ICS) assay	At Day 196

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: United States Department of Defense
• Investigators: Study Chair: Merlin Robb, MD, US Military HIV Research Program

Publications and helpful links

General Publications

• Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. doi: 10.2174/1566524033479825.
• Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B. Diversity considerations in HIV-1 vaccine selection. Science. 2002 Jun 28;296(5577):2354-60. doi: 10.1126/science.1070441.
• Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.
• Kibuuka H, Kimutai R, Maboko L, Sawe F, Schunk MS, Kroidl A, Shaffer D, Eller LA, Kibaya R, Eller MA, Schindler KB, Schuetz A, Millard M, Kroll J, Dally L, Hoelscher M, Bailer R, Cox JH, Marovich M, Birx DL, Graham BS, Michael NL, de Souza MS, Robb ML. A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172). J Infect Dis. 2010 Feb 15;201(4):600-7. doi: 10.1086/650299.
• Kibuuka H, Guwatudde D, Kimutai R, Maganga L, Maboko L, Watyema C, Sawe F, Shaffer D, Matsiko D, Millard M, Michael N, Wabwire-Mangen F, Robb M. Contraceptive use in women enrolled into preventive HIV vaccine trials: experience from a phase I/II trial in East Africa. PLoS One. 2009;4(4):e5164. doi: 10.1371/journal.pone.0005164. Epub 2009 Apr 10.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 22, 2005
• First Submitted That Met QC Criteria: July 22, 2005
• First Posted (Estimate): July 26, 2005

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: HIV Seronegativity; HIV Preventive Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: RV 172; 10381 (Registry Identifier: DAIDS ES Registry Number)