Clinical trial NCT00814762: Safety of the HIV Vaccine 732462 in HIV Infected Subjects Aged 18 to 55 Years Old
Official title: Study to Evaluate the Safety and Reactogenicity of the HIV Vaccine SB732462 in HIV Infected Subjects Aged 18 to 55 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: AIDS
Keywords: immunogenicity
HIV
reactogenicity
safety
vaccine
HIV Infections
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-12-25
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this research study is to evaluate the safety of GSK Biologicals' investigational HIV vaccine 732462, administered as two doses approximately 1 month apart, in a small group of HIV infected people.

Detailed description: This multicenter observer-blind study will determine the safety and reactogenicity of GSK Biologicals' investigational HIV vaccine 732462 in two sequentially enrolling cohorts of HIV-infected subjects treated with HAART (highly active antiretroviral therapy) and HIV infected treatment naïve subjects, respectively.

Eligibility criteria: Inclusion Criteria:

All subjects must satisfy the following criteria at screening and before vaccination:

* A male or female, aged between and including 18-55 years at the time of first vaccination.
* Known to be HIV-1 infected and under care of an HIV physician for a minimum of 6 months. However, subjects who initially presented with primary HIV infection need to have been diagnosed and under care for 12 months.
* 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.
* 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 throughout the duration of the study.
* CD4 count ≥ 450 cells per mm³

Additional inclusion criteria for subjects enrolled in the first cohort (HIV-infected subjects receiving HAART):

* Stable on highly active antiretroviral therapy (HAART) for at least one year.
* Undetectable viral load

Additional inclusion criteria for subjects enrolled in second cohort (treatment-naïve HIV-infected subjects):

* HAART-naïve (never received anti-retrovirals after HIV diagnosis)
* VL 5000-80000 copies/mL at screening
* Commencement of HAART is not expected based on current assessment within next year.

Exclusion Criteria:

The following criteria should be checked at the time of screening and before vaccination. If any apply, the subject must not be included in the study:

* Infection with HIV-2
* Had an AIDS defining illness (CDC Classification).
* Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the first dose of study vaccine/placebo, or planned use of any investigational or non-registered product other than the study vaccine during the study period.
* Drug therapy with immunomodulators or steroids within the three months preceding the first dose of study vaccine/placebo or planned administration during the study period
* Administration of immunoglobulins and/ or any blood products within the three months preceding the first dose of study vaccine/placebo or planned administration during the study period.
* Planned administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the first dose of study vaccine/placebo and ending at Month 4 It is recommended that the vaccination history of all subjects has been reviewed with their health care provider and that they have been encouraged to be fully vaccinated according to their country vaccination schedule for HIV- infected persons before enrolment into this study.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Any previous vaccination or immunotherapy against HIV.
* History of immune reconstitution disease when commencing antiretroviral therapy (for HIV-infected subjects receiving HAART)
* A family history of hereditary immunodeficiency.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* Acute or chronic infective hepatitis (A past history of hepatitis B or C is not an exclusion criterion).
* Acute or chronic, clinically relevant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* Any condition (including alcohol and drug abuse) which, in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol
* History of medically confirmed autoimmune disease
* History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure
* Asthma requiring daily steroid or long acting ß agonist prevention
* Unstable asthma defined as:

  * Sudden acute attacks occurring in less than three hours without an obvious trigger.
  * Hospitalisation for asthma in the last two years
* Food or wine induced asthma
* Known sensitivity to sulfites or aspirin
* Known sensitivity to aminoglycoside antibiotics

Primary outcomes:
measure: Number of subjects with solicited local symptoms
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of subjects with solicited general symptoms
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of subjects with unsolicited Adverse Events (AEs)
timeFrame: Day 0-Day 29 after each vaccination
measure: Number of subjects with Serious Adverse Events (SAEs) and medically attended visits
timeFrame: From Screening at Day -42 and up to the additional visit post study end, Month 12
measure: Number of subjects with study pre-defined Human Immunodeficiency Virus (HIV)-related adverse events
timeFrame: From Day 0 to study end at Month 12
measure: Number of subjects presenting abnormal biochemical and haematological values (any and grade ≥ 3)
timeFrame: From Day 0 to study end at Month 12
measure: Time to initiation of HAART therapy (for treatment-naïve HIV-infected subjects) or change in HAART therapy (for HIV-infected subjects receiving HAART)
timeFrame: From Day 0 to Month 12
Secondary outcomes:
measure: CD4 count and change of CD4 count from baseline
timeFrame: From Day 0 to Month 12
measure: Viral load and change in viral load from baseline
timeFrame: From Day 0 to Month 12
measure: Cluster of differentiation 40 ligand (CD40L+) CD4+ T-cell-mediated immune response (as measured by ICS)
timeFrame: Months 0, 4, 12 and at Day 44
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Harrer T, Plettenberg A, Arasteh K, Van Lunzen J, Fatkenheuer G, Jaeger H, Janssens M, Burny W, Collard A, Roman F, Loeliger A, Koutsoukos M, Bourguignon P, Lavreys L, Voss G. Safety and immunogenicity of an adjuvanted protein therapeutic HIV-1 vaccine in subjects with HIV-1 infection: a randomised placebo-controlled study. Vaccine. 2014 May 7;32(22):2657-65. doi: 10.1016/j.vaccine.2013.10.030. Epub 2013 Oct 19.