Efficacy and Safety of HIV Vaccine 732462 in ART-naïve HIV-1 Infected Persons
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 191
- 试验地点
- 1
- 主要终点
- Number of Subjects With Solicited Local Symptoms
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •This includes patients with dual infection with HIV-1/HIV-
- •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
研究组 & 干预措施
3D_HIV Group
HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 3 doses of the HIV Vaccine 732462 at Weeks 0, 4 and 28, administered intramuscularly in the deltoid of the non-dominant arm.
干预措施: GSK Biologicals HIV Vaccine 732462 (Biological)
2D_HIV Group
HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 2 doses of the HIV Vaccine 732462 at Weeks 0 and 4 and one dose of placebo (saline solution) at Week 28, administered intramuscularly in the deltoid of the non-dominant arm.
干预措施: GSK Biologicals HIV Vaccine 732462 (Biological)
2D_HIV Group
HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 2 doses of the HIV Vaccine 732462 at Weeks 0 and 4 and one dose of placebo (saline solution) at Week 28, administered intramuscularly in the deltoid of the non-dominant arm.
干预措施: Placebo (Drug)
Control Group
HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 3 doses of placebo (saline solution) at Weeks 0, 4 and 28, administered intramuscularly in the deltoid of the non-dominant arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Subjects With Solicited Local Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period, across doses
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of symptom regardless of intensity. Grade 3 Pain = pain that prevented normal every day activities. Grade 3 Redness/Swelling = redness or swelling associated with ulceration or secondary infection/phlebitis/sterile abscess/drainage. Medically attended (MA) Pain = pain causing inability to perform basic self-care function or Hospitalization indicated for management of pain. Medically attended Redness/Swelling = redness or swelling associated with necrosis.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: During the entire study period (up to Week 48)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Abnormal Haematological and Biochemical Values
时间窗: At Week 48
Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase \[ALT\], albumin \[ALB\], alkaline phosphatase \[ALP\], aspartate aminotransferase \[AST\], bilirubin (total) \[BIL\], creatinine \[CRE\], eosinophils \[EOS\], eosinophils/100 leukocytes \[EOS/100LEU\], bicarbonate \[BIC\], haemoglobin \[HGB\], potassium \[PTS\], lymphocytes \[LYM\], lymphocytes/100 leukocytes \[LYM/100LEU\], sodium \[SDI\], neutrophils \[NEU\], neutrophils/100 leukocytes \[NEU/100LEU\], platelet count \[PLC\], prothrombin time-international normalized ratio \[PTT\] and white blood cell count \[WBC\]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).
Geometric Mean Change in HIV-1 VL From Baseline
时间窗: At Week 48, post-Dose 3
Changes from baseline in HIV-1 viral load (difference of each value minus baseline value) were obtained using log10-transformed values and expressed in log10-RNA copies/mL. Baseline of HIV-1 viral load was defined as geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic.
Number of Subjects With Solicited General Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period, across doses
Assessed solicited general symptoms(smt.)were abdominalpain,anorexia,diarrhoea,fatigue,headache,myalgia,nausea,sweating,temperature(Temp.)orally=temp.37.7degreesCelsius(°C)\&vomiting.Any=occurrene of smt.regardless of intensity.Grade3(G3)Abdominal pain/fatigue/myalgia/sweating/headache=symp.causing inability to perform usual social\&functional activities.Medicallyattended(MA)Abdominalpain/fatigue/myalgia/sweating/headache=smt.causing inability to perform basic self-care activities.G3Anorexia=loss of appetite associated with significant weight loss.MAanorexia=aggressive intervention indicated.G3diarrhoea=blood/increased≥7stools per24hours(h)/4fluid replacement.G3nausea=persistent nausea resulting in minimal oral intake for more than48h/with aggressive rehydration indicated.G3vomiting=persistent vomiting resulting in orthostatic hypotension/aggressive.MAdiarrhoea/nausea/vomiting=smt.with life threatening consequences.Related=smt.assessed by the investigator as being related to vaccination
Number of Subjects With Unsolicited Adverse Events (AEs)
时间窗: During the 28-Day (Days 0-27) period following Dose 1 and Dose 2
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 (G3) AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were tabulated following Dose 1 and Dose 2 vaccinations.
Geometric Mean Change in Human Immunodeficiency Virus Type 1 (HIV-1) Viral Load (VL) From Baseline
时间窗: At Week 48, post-Dose 3
Changes from baseline in HIV-1 viral load (ratio of each value over baseline value) were obtained using crude values and expressed in RNA copies/milliliter \[copies/mL\]. Baseline of HIV-1 viral load was defined as geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic.
Number of Subjects With Unsolicited AEs
时间窗: During the 28-Day (Days 0-27) post-vaccination period
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 (G3) AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were tabulated following Dose 3 and across doses.
Number of Subjects With Potentially Immune-Mediated Diseases (pIMDs)
时间窗: During the entire study period (up to Week 48)
Potentially Immune-Mediated Diseases (pIMDs) are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.
次要结局
- Cluster of Differentiation 4 (CD4) Absolute Cell Count(At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48)
- Cytokine Expression Profile of F4co-Computed CD4+ T Cells(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))
- Magnitude of Antigen Specific Cluster of Differentiation-40 Ligand (CD40L)+CD4+ T-cells Expressing at Least Interleukin-2 (IL-2)(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))
- Cytokine Expression Profile of F4co-Computed CD8+ T Cells(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))
- Geometric Mean Change in HIV-1 Viral Load (LV) From Baseline(At Weeks 1, 4, 6, 16, 28, 30 and 38)
- Geometric Mean Change in HIV-1 VL From Baseline(At Weeks 1, 4, 6, 16, 28, 30 and 38)
- Levels of HIV-1 VL(At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48)
- Percentage of Subjects With Plasmatic HIV-1 Viral Load Decrease Higher Than (>) 1(At Week 48)
- Cytokine Expression Profile of P17 Antigen-specific CD8+ T-cells(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))
- Number of Seropositive Subjects for Anti-P24 Antibodies(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))
- Levels of HIV-1 Viral Load (VL)(At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48)
- Magnitude of Antigen Specific CD40L+CD4+ T-cells Expressing at Least One Cytokine(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))
- Magnitude of Antigen Specific CD40L-CD4+ T-cells Expressing at Least One Cytokine.(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))
- Magnitude of Antigen Specific CD4+ T-cells Expressing at Least One Cytokine(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))
- Number of Subjects With Response to at Least 1, 2, 3 or 4 Antigens(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))
- Cytokine Expression Profile of P24 Antigen-specific CD4+ T-cells(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))
- Cytokine Expression Profile of RT Antigen-specific CD4+ T-cells(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))
- Mean Change in CD4 Cell Count From Baseline(At Weeks 1, 4, 6, 16, 28, 30, 38 and 48)
- Percentage of Subjects With ART (Anti-Retroviral Therapy) Initiation and HIV-related Clinical Events(During the entire study period (up to Week 48))
- Magnitude of Antigen Specific CD8+ T-cells Expressing at Least One Cytokine(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))
- Number of Seropositive Subjects for Anti-F4co Antibodies(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))
- Cytokine Expression Profile of Nef Antigen-specific CD4+ T-cells(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))
- Cytokine Expression Profile of P17 Antigen-specific CD4+ T-cells(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))
- Cytokine Expression Profile of P24 Antigen-specific CD8+ T-cells(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))
- Number of Seropositive Subjects for Anti-P17 Antibodies(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))
- Number of Seropositive Subjects for Anti-RT Antibodies(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))
- Cytokine Expression Profile of Nef Antigen-specific CD8+ T-cells(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))
- Cytokine Expression Profile of RT Antigen-specific CD8+ T-cells(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))
- Number of Seropositive Subjects for Anti-Nef Antibodies(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))