Clinical trial NCT00123968: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: United States Department of Defense
First posted: 2005-07-26
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Local reactogenicity signs and symptoms
timeFrame: Throughout study
measure: Systemic reactogenicity signs and symptoms
timeFrame: Throughout study
measure: Laboratory measures of safety
timeFrame: Throughout study
measure: Adverse and serious adverse experiences
timeFrame: Throughout study
measure: Unfractionated IFN-gamma ELISPOT responses to HIV-1
timeFrame: At Day 196
measure: CD4+ and CD8+ T cell responses to HIV-1, as measured by flow cytometry-based intracellular cytokine staining (ICS) assay
timeFrame: At Day 196
Secondary outcomes:
Other outcomes:
Locations:
city: Kericho
country: Kenya
facility: Kenya Med. Research Inst./Walter Reed Project, Clinical Research Centre, Off Hospital Road. Kericho
city: Mbeya
country: Tanzania
facility: National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) CRS
city: Kampala
country: Uganda
facility: Makerere University Walter Reed Project (MUWRP)
Study officials:
affiliation: US Military HIV Research Program
name: Merlin Robb, MD
role: STUDY_CHAIR
References:
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