Dose-ranging Study to Evaluate the Safety & Immunogenicity of a HIV Vaccine 732461 in Healthy HIV Seronegative Volunteers

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00434512
First received: February 12, 2007
Last updated: October 27, 2011
Last verified: October 2011
  Purpose

GSK has constructed a new HIV immunogen comprised of conserved parts of the HIV virus (gag, pol and nef). The principal objectives of this study are to evaluate the reactogenicity and safety of this candidate vaccine with or without a GSK proprietary adjuvant system at three different doses and to evaluate the CD4+ T-cell response in terms of proportion of responders to the antigens two weeks after the second vaccination.


Condition Intervention Phase
Acquired ImmunoDeficiency Syndrome (AIDS)
Biological: HIV vaccine 732461
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Dose-ranging Study to Compare the Safety and Immunogenicity of a Candidate HIV Vaccine 732461, Adjuvanted or Not, Administered According to a 0, 1 Month Schedule to Healthy Adult HIV Seronegative Volunteers.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Occurrence, intensity and relationship to vaccination of solicited local and general symptoms [ Time Frame: During a 7-day (Day 0-6) follow-up period after each vaccination ] [ Designated as safety issue: No ]
  • Occurrence, intensity and relationship to vaccination of unsolicited symptoms [ Time Frame: During a 30-day (Day 0-29) follow-up period after each vaccination ] [ Designated as safety issue: No ]
  • Occurrence and relationship to vaccination of serious adverse events [ Time Frame: During the whole study period ] [ Designated as safety issue: No ]
  • Haematological and biochemical levels [ Time Frame: Months 0, 1, 2, 6, 7 9, 12 and at Day 44 in all subjects ] [ Designated as safety issue: No ]
  • Frequency of CD4+ T cells expressing at least two cytokines including IL-2 equal or above the cut-off to at least 1, 2, 3 antigens and to all 4 antigens [ Time Frame: Day 44 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L, as determined by ICS [ Time Frame: Months 0, 2, 6, 7, 12 and at Day 44 ] [ Designated as safety issue: No ]
  • Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing at least 2 cytokines including IL-2 equal or above the cut-off [ Time Frame: Months 0, 2, 6, 7, 12 and at Day 44 ] [ Designated as safety issue: No ]
  • Antibody titers to p17, p24, Nef, RT and F4co as measured by ELISA [ Time Frame: Months 0, 2, 6, 7, 12 and at Day 44 ] [ Designated as safety issue: No ]
  • Frequency of antigen specific CD4+ T cells to other HIV clades expressing IL-2 and/or TNF-a and/or IFN-g and/or CD40-L [ Time Frame: Day 44 and/or at Month 2 ] [ Designated as safety issue: No ]
  • Frequency of antigen specific CD8+ T cells expressing IL-2 and/or TNF-a and/or IFN-g and/or CD40-L [ Time Frame: Months 0, 2, 6, 12 and Day 44 ] [ Designated as safety issue: No ]
  • Frequency of antigen specific CD8+ T cells expressing at least 2 cytokines (IL-2, TNF-a, IFN-g or CD40-L) [ Time Frame: Months 0, 2, 6, 12 and Day 44 ] [ Designated as safety issue: No ]

Enrollment: 180
Study Start Date: February 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: HIV vaccine 732461
    Other Name: HIV vaccine 732461
Detailed Description:

This is a single center, observer-blind, randomized, dose-escalating, staggered study with 6 groups: 3 groups of 50 subjects receiving the adjuvanted candidate vaccine, at 3 different doses and 3 groups of 10 subjects receiving the non-adjuvanted candidate vaccine in water for injection, at 3 different doses. The vaccination schedule will be 0-1 month. Blood samples will be collected at 8 visits. The duration of the study will be approximately 14 months for each subject. Rationale for Protocol Posting Amendment: The third vaccination will be cancelled and the visit at Month 7 will be postponed to Month 9. The Protocol Posting has also been updated in order to comply with the FDA Amendment Act, Sep 2007.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A male or female between and including 18-40 years at the time of first vaccination.
  • Written informed consent obtained from the subject prior to any study procedure.
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
  • Good general health without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.
  • If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
  • Negative for antibodies against HIV-1, HIV-2 and negative for HIV p24 antigen within 56 days (8 weeks) prior to enrolment. Subjects must be willing to accept HIV test results. Individuals who elect not to receive test results will not be enrolled.
  • Negative for anti-HBc Ab, HBsAg and anti-HCV Ab.

Exclusion Criteria:

  • Women who are pregnant or breast-feeding.
  • Subjects with a history of, or current, alcohol or substance abuse.
  • The subject is at high risk of acquiring HIV according to the behavioural risk assessment questionnaire.
  • Morbid obesity
  • Previous inclusion in a HIV vaccines trial.
  • Receipt of live attenuated vaccines within 30 days of enrolment.
  • Receipt of medically indicated subunit or killed vaccines or allergy treatment with antigen injections within 14 days of study vaccine administration.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Prior receipt of HIV-1 vaccines or placebo in a previous HIV vaccine trial.
  • Receipt of blood products 120 days prior to HIV screening.
  • Receipt of immunoglobulin 120 days prior to HIV screening.
  • History of serious adverse reactions including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain to vaccines.
  • History of serious allergic reaction to any substance requiring hospitalization or emergency medical care.
  • History of immunodeficiency or autoimmune disease.
  • History of malignancy (unless there has been surgical excision followed by a sufficient observation period, of at least 5 years, to give a reasonable assurance of sustained cure and which, in the estimate of the investigator, is not likely to recur during the study period).
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccination.
  • History of type I or type II diabetes mellitus including cases controlled with diet alone. A subject with past gestational diabetes is eligible.
  • Thyroid disease including history of thyroidectomy and diagnoses requiring medication. A subject not requiring thyroid medicine within the past 12 months is eligible.
  • Acute disease at the time of enrolment.
  • Asthma requiring daily steroid or long acting β agonist prevention.
  • Unstable asthma.
  • Food- or wine-induced asthma.
  • Known sensitivity to sulfites or aspirin.
  • Bleeding disorder that was diagnosed by a physician. A subject who states that he or she has easy bruising or bleeding, but does not carry a formal diagnosis and has intramuscular (IM) injections and blood draws without any adverse experience is eligible.
  • History of any serious neurologic disorder or seizure
  • History of major congenital defect
  • History of chronic fatigue syndrome or fibromyalgia
  • Splenectomy
  • Hypertension. A subject with hypertension is eligible if he or she is controlled on medication and the documented blood pressure is less than 150/100.
  • Any medical, psychiatric or social condition, or occupational or other responsibility that, in the judgement of the investigator, would interfere with or serve as a contradiction to adherence to the study protocol or ability to give informed consent.
  Contacts and Locations
Choosing 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: NCT00434512

Locations
Belgium
GSK Investigational Site
Gent, Belgium, 9000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00434512     History of Changes
Other Study ID Numbers: 108706
Study First Received: February 12, 2007
Last Updated: October 27, 2011
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by GlaxoSmithKline:
Gag
vaccine
adjuvant
HIV
Pol
Nef

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014