Safety and Immune Response to a Prime-Boost Vaccination Schedule in HIV-infected Patients

Completed · Phase 1

Conditions studied: HIV

In brief

Study Design: This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety, tolerability and immune response of a prime-boost vaccination regimen for treatment of HIV infection. The vaccination schedule consists of three injections of a multiclade HIV plasmid DNA vaccine followed by one injection of a multiclade recombinant adenoviral vector vaccine (rAd), in HIV-infected adults. The hypothesis is that this vaccination regimen will be safe and elicit an immune response in HIV-infected subjects. The primary objectives are related to evaluating the safety and tolerability of the vaccination regimen and assessing the effect of vaccination on humoral and cellular immune responses to vaccine-specific HIV antigens. Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express clade B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed to express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Each DNA vaccination will be 1 mL of vaccine administered intramuscularly (IM) using the Biojector 2000 Needle-Free Injection Management System. Phosphate buffered saline (PBS) will be used as the placebo for the DNA vaccine. VRC-HIVADV014-00-VP (rAd) is a recombinant product composed of 4 adenoviral vectors (Ad) (in a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively. Injections of 10(10) PU will be administered IM by needle and syringe. The final formulation buffer (FFB) will be used as the placebo for the rAd vaccine. Subjects: HIV-infected adult volunteers (18-50 years old) on stable highly active antiretroviral therapy (HAART) therapy who have a CD4+ cell count greater than 350 cells/mm3 and have had a viral load (VL) less than 400 copies/mL for at least six months and a viral load of less than 50 copies/mL within 4 weeks prior to enrollment. Study Plan: Fifteen volunteers will be enrolled and randomized in a 2:1 ratio to vaccine:control (10 DNA prime with rAd boost:5 PBS with FFB placebo). A Data and Safety Monitoring Board (DSMB) will review the study every 6 months. Subjects will be evaluated for safety and immunogenicity for 48 weeks, which is 24 weeks after the target date for the booster vaccination. Study Duration: Subjects will be followed for 48 weeks after enrollment into the study.

Key facts

Study ID

NCT00270465

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

17

Starts

2005-12-21

Expected to finish

2009-06-25

Last updated by the study team

2017-07-02

Who can join

Age: 18 and older, up to 50. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Women:
• Breast-feeding or planning to become pregnant during the 48 weeks of study participation.
• A volunteer will be excluded if he/she has a medication history of one or more of the following:
• Receipt of live attenuated vaccines or investigational research agents within 30 days prior to study entry.
• Receipt of blood products within 120 days prior to study entry.
• Receipt of immunoglobulin within 60 days prior to study entry.
• Receipt of medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal, or allergy treatment with antigen injections) within 14 days prior to study entry.
• Receipt of experimental HIV vaccines in the preceding 2 years. Individuals that received a placebo in a prior HIV vaccine trial are not excluded.
• Receipt of immunosuppressive medications within the past 6 months (e.g., oral/parenteral/inhaled corticosteroids, and/or cytotoxic medications). NOTE: The following will be allowed: corticosteroid nasal spray for allergic rhinitis; topical corticosteroids for acute, uncomplicated dermatitis; over the counter medications for acute, uncomplicated dermatitis for a period not longer than 14 days; 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 the study.
• Receipt of IL-2 within the preceding 1 year.
• A volunteer with any of the following conditions will be excluded:
• Positive hepatitis B virus (HBV) surface antigen or positive hepatitis C virus (HCV) antibody or detectable HCV viral load.
• History of CD4+ counts less than 100 cells/mm(3) on two or more occasions in the past.
• History of serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Subjects who have a history of an adverse reaction to pertussis vaccine as a child may enroll.
• History of autoimmune disease; immunodeficiency (other than HIV infection); asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the prior 2 years or that requires the use of oral or intravenous corticosteroids; diabetes (Type I or II with the exception of gestational diabetes); thyroidectomy or history of thyroid disease in the past 12 months; or serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years.
• Current antituberculosis-prophylaxis or therapy.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 14 days prior to study entry.
• Hypertension that is not well controlled by medication or is more than 150/100 at enrollment.
• Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular (IM) injections or blood draws.
• Syphilis infection that is active or a positive serology due to a syphilis infection that has not been effectively treated.
• Treated malignancy for which there is not reasonable assurance of sustained cure, or malignancy that required either lymph node irradiation or axillary dissection.
• Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years.
• Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicide plan or attempt occurring within five years prior to enrollment.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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