Evaluation of the Immune Response of a HIV Candidate Vaccine After Administration of One Chloroquine Dose

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and reactogenicity of one booster dose of a HIV candidate vaccine after administration of one oral dose of chloroquine.

Detailed Description
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The Protocol Posting has been updated following Protocol amendment 1, October 2009.

Official Title
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A Study to Evaluate the Safety and Immunogenicity of a Booster Dose of GSK Biologicals' HIV Candidate Vaccine (732461) After Administration of Chloroquine in Healthy Adults.

Conditions
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AIDS

Intervention / Treatment
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* Biological: GSK Biologicals' HIV vaccine (732461)
* Drug: Chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female between, and including, 18 to 52 years of age at the time of vaccination. Written informed consent prior to any study related procedure on the subject. Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Good general health without significant medical history or physical examination findings. Negative for anti-HBc and anti-Hepatitis C Virus antibodies. Female subjects of non-childbearing potential may be enrolled in the study. 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 on the day of vaccination, and has agreed to continue adequate contraception until study completion. Previous participation and completion of the study NCT00434512. Cellular and humoral immune responder to vaccines administered in study NCT00434512. Subjects must be willing to accept HIV test results. Individuals who elect not to receive test results will not be enrolled. Exclusion Criteria: Clinically significant laboratory value above normal range for blood urea nitrogen, creatinine, alanine aminotransferase and aspartate aminotransferase, or clinically significant laboratory value above or below normal range for Hemoglobin, as per investigator judgment. Women who are pregnant or breast-feeding. Receipt of live attenuated vaccines within 30 days of vaccination. Receipt of medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) or allergy treatment with antigen injections (including a tuberculin skin test) within <= 21days preceding and planned <= 21 days following the study vaccine administration. Receipt of blood products 120 days prior to vaccination. Receipt of immunoglobulin 120 days prior to vaccination. Subject has donated blood in the last 3 months. Bleeding disorder that was diagnosed by a physician; e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first. History of serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/product. History of serious allergic reaction to any substance requiring hospitalization or emergency medical care. History of hypersensitivity against chloroquine or any components of the drug. History of hypersensitivity against aminoglycosides. Ophthalmologic findings at screening. Previous administration of 4-aminoquinoline in the previous year or for a duration of more than 1 year. History of Glucose-6-Phosphate Dehydrogenase deficiency. History of hematopoietic disease. History of Myasthenia gravis. History of any serious neurological disorder or seizure. History of immunodeficiency or immune-mediated disorders, including active psoriasis. History of type I or type II diabetes mellitus including cases controlled with diet alone. Thyroid disease including history of thyroidectomy and diagnoses requiring medication. Asthma requiring daily steroid or long acting β-agonist prevention. Unstable asthma defined as: Sudden acute attacks occurring in less than three hours without an obvious trigger. Hospitalization for asthma in the last two years. Food- or wine-induced asthma. Known sensitivity to sulfites or aspirin. History of major congenital defect. History of chronic fatigue syndrome or fibromyalgia. History of malignancy. Splenectomy. Morbid obesity. Clinically relevant hypertension. Subjects with a history of, or current, alcohol or substance abuse. Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccines, or planned use during the study period. 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). Previous inclusion in a HIV vaccines trial other than study NCT00434512. Subject is seropositive for HIV, as determined by the test results performed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 52 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK732461+Nivaquine Group<br>Subjects received a single dose of Nivaquine® tablets orally, 2 days prior to receiving a booster dose of the GSK732461 vaccine. | Biological: GSK Biologicals' HIV vaccine (732461)<br>* 1 dose intramuscular injection<br>Drug: Chloroquine<br>* One dose of 300 mg<br>* Other names: Nivaquine®;|
| Active Comparator: GSK732461 Group<br>Subjects received a booster dose of the GSK732461 vaccine intramuscularly, in the deltoid region of the non-dominant arm. | Biological: GSK Biologicals' HIV vaccine (732461)<br>* 1 dose intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Frequency of Cluster of Differentiation 8 (CD8+) T Cells Expressing at Least One Cytokine to at Least 1, 2, 3 or All 4 Antigens | Among expressed cytokines were interleukin-2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as determined by intracellular cytokine staining (ICS). | At Day 14 | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 7 Day (Days 0-6) post-vaccination period | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were fatigue, temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain] and headache. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7 Day (Days 0-6) post-vaccination period | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | 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 out-side 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 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During the 32 Day (Days 2-29) post-chloroquine administration and during the 30 Day (Days 0-29) post-vaccine administration period | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | During the entire study period (from Day 0 up to Day 360) | 
| Number of Subjects With AEs of Specific Interest and Immune-Mediated Disorders (IMDs) | Adverse events of specific interest include auto-immune diseases (AID) and immune mediated disorders such as neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, other autoimmune/inflammatory events. | During the entire study period (from Day 0 up to Day 360) | 
| Levels of Haematological and Biochemical Parameters | Among haematological and biochemical parameters determined were alanine aminotransferase [ALT], aspartate aminotransferase [ASA], basophils [BASO], creatinine [CREA], eosinophils [EOS], haematocrit [HAEM], haemoglobin [HAEMO], lymphocytes [LYMPH], monocytes [MONO], neutrophils [NEU], platelets [PLA], red blood cells [RBC], urea [UR] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - unknown, below, within and above. | At Day 0 | 
| Levels of Haematological and Biochemical Parameters | Among haematological and biochemical parameters determined were alanine aminotransferase [ALT], aspartate aminotransferase [ASA], basophils [BASO], creatinine [CREA], eosinophils [EOS], haematocrit [HAEM], haemoglobin [HAEMO], lymphocytes [LYMPH], monocytes [MONO], neutrophils [NEU], platelets [PLA], red blood cells [RBC], urea [UR] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - unknown, below, within and above. | At Day 7 | 
| Levels of Haematological and Biochemical Parameters | Among haematological and biochemical parameters determined were alanine aminotransferase [ALT], aspartate aminotransferase [ASA], basophils [BASO], creatinine [CREA], eosinophils [EOS], haematocrit [HAEM], haemoglobin [HAEMO], lymphocytes [LYMPH], monocytes [MONO], neutrophils [NEU], platelets [PLA], red blood cells [RBC], urea [UR] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - unknown, below, within and above. | At Day 30 | 
| Levels of Haematological and Biochemical Parameters | Among haematological and biochemical parameters determined were alanine aminotransferase [ALT], aspartate aminotransferase [ASA], basophils [BASO], creatinine [CREA], eosinophils [EOS], haematocrit [HAEM], haemoglobin [HAEMO], lymphocytes [LYMPH], monocytes [MONO], neutrophils [NEU], platelets [PLA], red blood cells [RBC], urea [UR] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - unknown, below, within and above. | At Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of Antigen Specific CD8+ T Cells Expressing at Least One Cytokine | Magnitude was defined as the frequency of CD8+ T cells group-specific antigen (Gag) proteins 17, 24; negative regulatory factor (Nef); reverse transcriptase (RT) and fusion protein of all 4 antigens (F4co). Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD8+ T cell response to each of the 4 antigens (F4co_est). Among the cytokines expressed were IL-2, TNF-α and INF-γ. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or cluster of differentiation 40-ligand (CD40-L) cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or cluster of differentiation 40-ligand (CD40-L) cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (p17) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (p24) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (pool_F4co) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD8+ T cell response to each of the 4 antigens (F4co_est). | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (F4co_est) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine | Cytokine/marker co-expression profile was defined as the antigen-specific CD8+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD8+ T cell response to each of the 4 antigens (F4co_est). | At Day 0, 7, 14, 30 and 180 | 
| Number of Subjects With Frequency of Cluster of Differentiation (CD4+) T Cells Expressing at Least 2 Cytokines to at Least 1, 2, 3 or All 4 Antigens | Among expressed cytokines were interleukin-2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Magnitude of Antigen Specific CD4+ T Cells Expressing at Least 2 Cytokines | Magnitude was defined as the frequency of CD4+ T cells group-specific antigen (Gag) proteins 17, 24, negative regulatory factor (Nef), reverse transcriptase (RT) and fusion protein of all 4 antigens (F4co). Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD8+ T cell response to each of the 4 antigens (F4co_est). Among the cytokines expressed were IL-2, TNF-α and INF-γ. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (RT) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (Nef) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (p17) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (p24) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD4+ T cell response to each of the 4 antigens (F4co_est). | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD4+ T cell response to each of the 4 antigens (F4co_est). | At Day 0, 7, 14, 30 and 180 | 
| Frequency of Antigen (F4co_est) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines | Cytokine/marker co-expression profile was defined as the antigen-specific CD4+ T cells expressing IL-2 and/or TNF-α and/or IFN-γ and/or CD40-L cytokines as determined by ICS. Determination of F4co was done by stimulating the F4 antigen with a peptide pool spanning (pool_F4co) or by adding individual frequencies of the CD4+ T cell response to each of the 4 antigens (F4co_est). | At Day 0, 7, 14, 30 and 180 | 
| Anti- RT, Nef, p17, p24 and F4co Antibody Concentrations | Antibody concentrations were expressed as geometric mean concentrations (GMCs), given in milli-enzyme-linked immunosorbent assay (ELISA) units per millilitre (mEL.U/mL). | At Day 0, 7, 14, 30 and 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chloroquine, Human Immunodeficiency Virus