Clinical trial NCT01218113: Efficacy and Safety of GSK Biologicals HIV Vaccine in Antiretroviral Therapy (ART)-naïve HIV-1 Infected Persons
Official title: Efficacy and Safety of HIV Vaccine 732462 in ART-naïve HIV-1 Infected Persons
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AIDS
Keywords: Human Immunodeficiency Virus (HIV)-1
safety
vaccine
immunogenicity
reactogenicity
HIV infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-10-11
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to determine whether administration of the GSK Biologicals HIV vaccine 732462 can lead to a reduction in viral load, and impact on the course of human immunodeficiency virus type 1 (HIV-1) infection. In HIV-1 infected persons who have not yet started antiretroviral therapy (ART), such a vaccine would potentially lead to a delay in the initiation of treatment.


Eligibility criteria: Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

* Subjects who the investigator believes can and will comply with the requirements of the protocol.
* Written informed consent obtained from the subject prior to any study procedure.
* A male or female between and including 18-55 years at the time of first vaccination.
* Known to be HIV-1 infected and under the care of an HIV physician for a minimum of 6 months. However, subjects who initially presented with a clinical diagnosis of primary HIV infection need to have been diagnosed and under care for at least 12 months.
* ART-naïve. Individuals must never have received ART after HIV diagnosis, including lamivudine used for chronic hepatitis B infection, with the exception of short-term ART for prevention of mother-to-child transmission (PMTCT) at least 12 months prior to enrollment.
* Commencement of ART is not expected, based on current assessment, within the next 12 months.
* Viral load level of 2,000-80,000 copies/mL at screening.
* CD4 count \>= 500 cells per mm3 at screening.
* If the subject is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal. Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test at screening, and
  * has agreed to continue adequate contraception during the entire study period.

Exclusion Criteria:

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

* Infection with HIV-2. This includes patients with dual infection with HIV-1/HIV-2.
* Had an Acquired Immune Deficiency Syndrome (AIDS) defining clinical illness.
* Use of any investigational or non-registered product within 4 weeks 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 12 weeks preceding the first dose of study vaccine/placebo or planned administration during the study period. Acute use of steroids up to 4 weeks preceding the first dose for treatment of hypersensitivity reactions is not an exclusion criterion. Inhaled and topical steroids are allowed.
* Administration of immunoglobulins and/ or any blood products within the 12 weeks 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 2 weeks before the first dose of study vaccine/placebo and ending at Visit 3 (Week 6) (after blood sampling),
  * the period starting from 2 weeks prior to Visit 5 (Week 28) and ending at Visit 6 (Week 30) (after blood sampling)
  * the period starting from 2 weeks prior to Visit 8 (Week 48) and ending at Visit 8 (Week 48) (after blood sampling), with the exception of non-adjuvanted influenza vaccine.
* 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.
* Any previous vaccination or immunotherapy against HIV.
* 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.
* Acute or chronic, clinically relevant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination and/or medical history at screening.
* Grade 3 or grade 4 laboratory abnormality, as defined by Division od AIDS (DAIDS) grading table, at screening
* Pregnant or lactating female.
* Any condition 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.
* Unstable asthma
* Food or wine induced asthma.
* Known sensitivity to sulfites or aspirin.
* Known sensitivity to aminoglycoside antibiotics.
* Contraindication to intramuscular injection

Primary outcomes:
measure: Geometric Mean Change in Human Immunodeficiency Virus Type 1 (HIV-1) Viral Load (VL) From Baseline
timeFrame: At Week 48, post-Dose 3
measure: Geometric Mean Change in HIV-1 VL From Baseline
timeFrame: At Week 48, post-Dose 3
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 1
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 2
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 3
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period, across doses
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 1
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 2
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) period following Dose 3
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7-day (Days 0-6) post-vaccination period, across doses
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 28-Day (Days 0-27) period following Dose 1 and Dose 2
measure: Number of Subjects With Unsolicited AEs
timeFrame: During the 28-Day (Days 0-27) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (up to Week 48)
measure: Number of Subjects With Potentially Immune-Mediated Diseases (pIMDs)
timeFrame: During the entire study period (up to Week 48)
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Screening
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: Pre-vaccination, at Week 0
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 4
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 6
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 16
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 28
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 30
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 38
measure: Number of Subjects With Abnormal Haematological and Biochemical Values
timeFrame: At Week 48
Secondary outcomes:
measure: Geometric Mean Change in HIV-1 Viral Load (LV) From Baseline
timeFrame: At Weeks 1, 4, 6, 16, 28, 30 and 38
measure: Geometric Mean Change in HIV-1 VL From Baseline
timeFrame: At Weeks 1, 4, 6, 16, 28, 30 and 38
measure: Levels of HIV-1 Viral Load (VL)
timeFrame: At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
measure: Levels of HIV-1 VL
timeFrame: At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
measure: Percentage of Subjects With Plasmatic HIV-1 Viral Load Decrease Higher Than (>) 1
timeFrame: At Week 48
measure: Cluster of Differentiation 4 (CD4) Absolute Cell Count
timeFrame: At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
measure: Mean Change in CD4 Cell Count From Baseline
timeFrame: At Weeks 1, 4, 6, 16, 28, 30, 38 and 48
measure: Percentage of Subjects With ART (Anti-Retroviral Therapy) Initiation and HIV-related Clinical Events
timeFrame: During the entire study period (up to Week 48)
measure: Magnitude of Antigen Specific Cluster of Differentiation-40 Ligand (CD40L)+CD4+ T-cells Expressing at Least Interleukin-2 (IL-2)
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Magnitude of Antigen Specific CD40L+CD4+ T-cells Expressing at Least One Cytokine
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Magnitude of Antigen Specific CD40L-CD4+ T-cells Expressing at Least One Cytokine.
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Magnitude of Antigen Specific CD4+ T-cells Expressing at Least One Cytokine
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Magnitude of Antigen Specific CD8+ T-cells Expressing at Least One Cytokine
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Subjects With Response to at Least 1, 2, 3 or 4 Antigens
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of F4co-Computed CD4+ T Cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of Nef Antigen-specific CD4+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of P17 Antigen-specific CD4+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of P24 Antigen-specific CD4+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of RT Antigen-specific CD4+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of F4co-Computed CD8+ T Cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of Nef Antigen-specific CD8+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of P17 Antigen-specific CD8+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of P24 Antigen-specific CD8+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Cytokine Expression Profile of RT Antigen-specific CD8+ T-cells
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Seropositive Subjects for Anti-P17 Antibodies
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Seropositive Subjects for Anti-P24 Antibodies
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Seropositive Subjects for Anti-Nef Antibodies
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Seropositive Subjects for Anti-RT Antibodies
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
measure: Number of Seropositive Subjects for Anti-F4co Antibodies
timeFrame: During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Camden
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Somers Point
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Johnson City
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Annandale
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Bobigny
country: France
facility: GSK Investigational Site
city: Créteil
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Paris Cedex 12
country: France
facility: GSK Investigational Site
city: Paris Cedex 13
country: France
facility: GSK Investigational Site
city: Paris cedex 15
country: France
facility: GSK Investigational Site
city: Paris Cedex 20
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Móstoles, Madrid
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: