Safety and Immune Response to a Prime-Boost Vaccination Schedule in HIV-infected Patients
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party)
National Institutes of Health Clinical Center (CC)
First received: December 24, 2005
Last updated: June 30, 2017
Last Verified: June 25, 2009
History of Changes
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.
Drug : VRC-HIVDNA016-00-VP
Drug : VRC-HIVADV014-00-VP
Primary Purpose: Treatment
|Official Title:||VRC101: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Prime-Boost HIV-1 Vaccination Schedule of a 6-Plasmid Multiclade HIV-1 DNA Vaccine, VRC-HIVDNA016-00-VP, Followed by a Recombinant Multiclade Adenoviral Vector HIV Vaccine|
Further study details as provided by National Institutes of Health Clinical Center (CC):
|Study Start Date:||December 21, 2005|
|Study Completion Date:||June 25, 2009|
|Primary Completion Date:||June 25, 2009 (Final data collection date for primary outcome measure)|
This study will determine the safety and side effects of two experimental HIV vaccines and
see if vaccination can enhance the pre-existing HIV-specific immune response in HIV-infected
individuals on anti-retroviral therapy . The vaccines are VRC-HIVDNA016-00-VP (called the
"DNA vaccine") and VRC-HIVADV014-00-VP (called the "rAd vaccine"). The DNA vaccine codes for
four HIV proteins. The rAd vaccine is made using an adenovirus (a common virus that causes
upper respiratory infections, such as the common cold) that has been modified to contain DNA
that codes for three HIV proteins. These vaccines will be given in a "prime-boost" schedule
and cannot cause HIV or adenoviral infections.
HIV-infected people between 18 and 50 years old who are on a stable treatment plan for HIV with highly active antiretroviral (ARV) drugs, have a CD4+ T cell count greater than 350, and have a low viral load may be eligible for this 48-week study.
Participants receive an injection (shot) of the DNA vaccine or a placebo (solution that does not contain any vaccine, medicine, or drugs) the day they enter the study and again at study weeks 4 and 8. They receive a booster injection of the rAd vaccine or placebo at week 24. The DNA vaccines are given with a needle-less injection device called the "Biojector 2000(Registered Trademark)" and the rAd vaccine is given using a needle and syringe. All shots are given in the upper arm muscle, alternating right and left arms with each injection. Patients fill out a diary card at home for 5 days after each vaccination, recording their temperature and any symptoms. The cards are turned in to the clinic at the first visit after all 5 days are completed. Patients must call a study nurse 1 or 2 days after each of the four injections and again 7 or 8 days after each of the first three injections.
Patients have 12 clinic visits during the course of the study. At each visit, they are checked for health changes or problems, asked how they are feeling and if they have taken any medications or other treatments, including over-the-counter medicines, herbal supplements, etc. Blood samples are drawn at every visit and urine samples are collected at some visits.
At week 28 (4 weeks after the fourth injection), patients undergo apheresis, a procedure for collecting large numbers of white blood cells. The cells are tested in the laboratory to see how the immune system responds to the study vaccine. For the procedures, blood is collected through a needle in an arm vein and spun in a machine that separates the white blood cells from the rest of the blood (red cells, plasma and platelets). The white cells are removed and the rest of the blood is returned to the patient's body through the same needle. Patients who cannot or do not want to undergo apheresis have 80 mL (about 1/3 cup) of blood drawn through a needle and collected in blood collection tubes.
|Ages Eligible for Study:||18 Years to 50 Years|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
A participant must meet all of the following criteria:
- HIV-1 infection defined as documented by any approved ELISA test kit and confirmed with a Western blot at any time prior to study entry.
- On stable highly active antiretroviral therapy (HAART), as defined by the Department of Health and Human Services (http://www.aidsinfo.nih.gov/other/cbrochure/english/04_en.pdf), with no change in the drugs included in the treatment regimen for a minimum of 8 weeks prior to enrollment.
- CD4+ cell count greater than 350 cells/mm(3) at 2 different time points that meet the following criteria: The first result must be from between 4 weeks to 36 weeks prior to enrollment obtained at any laboratory used by a health care facility. The second result must be obtained at the NIH Clinical Center within 28 days prior to enrollment. There must be at least 28 days between the two tests used for eligibility.
- HIV-1 RNA viral load (VL) consistently less than 400 copies/mL for six months or longer prior to enrollment (as reported by the subject). Documentation must include the following: at least one documented HIV RNA PCR result showing VL less than 400 copies/mL obtained between 12-36 weeks prior to enrollment at any laboratory used by a health care facility and another VL less than 50 copies/mL that must be obtained at the NIH Clinical Center within 28 days prior to study entry.
- Men and women aged 18-50 years.
- Ability and willingness of subject to give written informed consent.
Laboratory Criteria within 28 days prior to enrollment:
Condoms (male or female) with or without a spermicidal agent;
Diaphragm or cervical cap with spermicide;
If the female volunteer is not of reproductive potential as defined above she is eligible without requiring the use of contraception. Patient-reported history is acceptable as documentation of sterilization, contraceptive methods, or menopause.
- Breast-feeding or planning to become pregnant during the 48 weeks of study participation.
- 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.
- 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.
- Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
A volunteer will be excluded if he/she has a medication history of one or more of the following:
A volunteer with any of the following conditions will be excluded:
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00270465
Locations Show More
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
|Responsible Party:||National Institute of Allergy and Infectious Diseases (NIAID)|
|ClinicalTrials.gov Identifier:||NCT00270465 History of Changes|
|Other Study ID Numbers:||060056|
|Study First Received:||December 24, 2005|
|Last Updated:||June 30, 2017|
Keywords provided by National Institutes of Health Clinical Center (CC):HIV-positive
ClinicalTrials.gov processed this data on November 20, 2018
This information is provided by ClinicalTrials.gov.