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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00972725
First received: September 3, 2009
Last updated: March 2, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
AIDS Biological: GSK Biologicals' HIV vaccine (732461) Drug: Chloroquine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Prevention
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: At Day 14 ]
    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).

  • Number of Subjects With Solicited Local Symptoms [ Time Frame: During the 7 Day (Days 0-6) post-vaccination period ]
    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.

  • Number of Subjects With Solicited General Symptoms [ Time Frame: During the 7 Day (Days 0-6) post-vaccination period ]
    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.

  • Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: During the 32 Day (Days 2-29) post-chloroquine administration and during the 30 Day (Days 0-29) post-vaccine administration 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 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.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (from Day 0 up to Day 360) ]
    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 AEs of Specific Interest and Immune-Mediated Disorders (IMDs) [ Time Frame: During the entire study period (from Day 0 up to Day 360) ]
    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.

  • Levels of Haematological and Biochemical Parameters [ Time Frame: At Day 0 ]
    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.

  • Levels of Haematological and Biochemical Parameters [ Time Frame: At Day 7 ]
    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.

  • Levels of Haematological and Biochemical Parameters [ Time Frame: At Day 30 ]
    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.

  • Levels of Haematological and Biochemical Parameters [ Time Frame: At Day 180 ]
    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.


Secondary Outcome Measures:
  • Magnitude of Antigen Specific CD8+ T Cells Expressing at Least One Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (p17) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (p24) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (pool_F4co) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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).

  • Frequency of Antigen (F4co_est) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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).

  • 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 [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    Among expressed cytokines were interleukin-2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as determined by ICS.

  • Magnitude of Antigen Specific CD4+ T Cells Expressing at Least 2 Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (RT) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (Nef) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (p17) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (p24) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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.

  • Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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).

  • Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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).

  • Frequency of Antigen (F4co_est) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    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).

  • Anti- RT, Nef, p17, p24 and F4co Antibody Concentrations [ Time Frame: At Day 0, 7, 14, 30 and 180 ]
    Antibody concentrations were expressed as geometric mean concentrations (GMCs), given in milli-enzyme-linked immunosorbent assay (ELISA) units per millilitre (mEL.U/mL).


Enrollment: 28
Study Start Date: December 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK732461+Nivaquine Group
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)
1 dose intramuscular injection
Drug: Chloroquine
One dose of 300 mg
Other Name: Nivaquine®
Active Comparator: GSK732461 Group
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)
1 dose intramuscular injection

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

Ages Eligible for Study:   18 Years to 52 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00972725

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00972725     History of Changes
Other Study ID Numbers: 113165
Study First Received: September 3, 2009
Results First Received: November 28, 2016
Last Updated: March 2, 2017

Keywords provided by GlaxoSmithKline:
Chloroquine
Human Immunodeficiency Virus

Additional relevant MeSH terms:
Vaccines
Chloroquine
Chloroquine diphosphate
Immunologic Factors
Physiological Effects of Drugs
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics

ClinicalTrials.gov processed this record on August 16, 2017