Phase 1 Safety Study of Two Experimental HIV Vaccines
|First Received Date ICMJE||May 26, 2007|
|Last Updated Date||October 9, 2014|
|Start Date ICMJE||May 2007|
|Primary Completion Date||May 2014 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Safety (local and systemic reactogenicity, lab tests, AEs)|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00479999 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Immunogenicity (cellular and humoral immune function assays)|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Phase 1 Safety Study of Two Experimental HIV Vaccines|
|Official Title ICMJE||VRC 012: A Phase I Clinical Trial of the Safety and Immunogenicity of an HIV-1 Adenoviral Vector Serotype 35 Vaccine: Dose Escalation as a Single Agent and Prime-Boost Schedules With an HIV-1 Adenoviral Vector Serotype 5 Vaccine in Uninfected Adults|
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.
The VRC recombinant adenoviral vector serotype 5 (rAd5) multiclade vaccine has been previously shown to elicit immune responses to HIV-1-specific peptides when administered intramuscularly (IM) alone and in prime-boost schedules with the greatest magnitude and frequency of response to the Envelope A immunogen (EnvA).
Part I of this study is an open label, dose escalation evaluation of an HIV-1 adenoviral vector serotype 35 vaccine (rAd35-EnvA).
Subjects in Group 1 will receive one vaccination of rAd35-EnvA 10(9) PU.
Subjects in Group 2 will receive one vaccination of rAd35-EnvA 10(10) PU.
Subjects in Group 3 will receive one vaccination of rAd35-EnvA 10(11) PU.
Part II (Group 4) of this study is a randomized, double blind evaluation of the rAd35-EnvA vaccine in comparison to and in combination with a rAd5-EnvA vaccine in prime-boost schedules.
The hypotheses are: 1) rAd35-EnvA vaccine will be safe for human administration at dosages up to 10(11) PU as a single agent and both the rAd35-EnvA and rAd5-EnvA vaccines will be safe in prime-boost regimens; 2) both the rAd35-EnvA and rAd5-EnvA vaccines will elicit immune responses to the EnvA immunogen and 3) the heterologous prime-boost regimens will elicit a greater frequency and magnitude of response than after the priming vaccinations alone. The primary objectives relate to evaluation of the safety and tolerability of the rAd35-EnvA and rAd5-EnvA vaccines. Secondary objectives are related to evaluation of the immunogenicity of the vaccines when comparing rAd35-EnvA to rAd5-EnvA when administered as a prime or as a boost vaccination.
Product Description: Both the VRC-HIVADV038-00-VP (rAd5-EnvA) and the VRC-HIVADV027-00-VP (rAd35-EnvA) vaccines are composed of recombinant, replication deficient adenoviral vectors that encode for HIV-1 clade A Env glycoprotein.
Subjects: Thirty-five healthy adult volunteers, 18 to 50 years old; beginning with the Version 2.0 protocol, subjects in Part I must be Ad35 antibody (Ab) seronegative and subjects in Part II must be both Ad5- and Ad35-seronegative.
Study Plan: Part I: Fifteen subjects will receive an open-label 1 mL IM deltoid injection via needle and syringe of the study agent. No more than one subject per day will be enrolled into each dose group. Five days following vaccination of the fifth volunteer in each dose group, there will be an internal safety review including the principal investigator, clinical team and medical officer to determine whether to proceed to next dose level.
Part II: Initiation of enrollment into Part II will be contingent upon completion of enrollment into Group 3 and a safety review of 10(9) and 10(10) PU dosage by the Data and Safety Monitoring Board (DSMB). The safety review will take place when at least 2 weeks of follow-up on the last 10(10) PU injection in Group 2 is available in the safety reports; the DSMB safety review may occur during enrollment of Group 3.
Enrollment into Group 4 will be randomized and double-blinded. The first 10 subjects in Group 4 will be randomized in a 1:1 ratio into heterologous prime-boost vaccination schedules in which both rAd5-EnvA and rAd35-EnvA are administered at the 10(10) PU dosage. The last 10 subjects in Group 4 will be randomized in a 1:1 ratio into heterologous prime-boost vaccination schedules in which the rAd5-EnvA is administered at 10(10) PU and rAd35-EnvA is administered at 10(11) PU. All subjects will receive each study agent administered as 1 mL IM deltoid injections (12 weeks apart) according to the schedule.
The vaccination regimen and clinical follow-up schedule for Part I requires 24 weeks and for Part II requires 52 weeks to complete. Part II subjects will be contacted annually for 4 years after study completion for collection of long-term follow-up information.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||May 2014|
|Primary Completion Date||May 2014 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
A participant must meet all of the following criteria:
No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 12 of the study for subjects in Part I and through Week 24 of the study for subjects in Part II,
Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 12 of the study for subjects in Part I or through Week 24 of the study for subjects in Part II by one of the following methods:
A volunteer will be excluded if one or more of the following conditions apply:
|Ages||18 Years to 50 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00479999|
|Other Study ID Numbers ICMJE||070167, 07-I-0167|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||May 2014|
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