Clinical trial NCT00972725: Evaluation of the Immune Response of a HIV Candidate Vaccine After Administration of One Chloroquine Dose
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AIDS
Keywords: Chloroquine
Human Immunodeficiency Virus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-09-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: The Protocol Posting has been updated following Protocol amendment 1, October 2009.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: At Day 14
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 7 Day (Days 0-6) post-vaccination period
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 7 Day (Days 0-6) post-vaccination period
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 32 Day (Days 2-29) post-chloroquine administration and during the 30 Day (Days 0-29) post-vaccine administration period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 up to Day 360)
measure: Number of Subjects With AEs of Specific Interest and Immune-Mediated Disorders (IMDs)
timeFrame: During the entire study period (from Day 0 up to Day 360)
measure: Levels of Haematological and Biochemical Parameters
timeFrame: At Day 0
measure: Levels of Haematological and Biochemical Parameters
timeFrame: At Day 7
measure: Levels of Haematological and Biochemical Parameters
timeFrame: At Day 30
measure: Levels of Haematological and Biochemical Parameters
timeFrame: At Day 180
Secondary outcomes:
measure: Magnitude of Antigen Specific CD8+ T Cells Expressing at Least One Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (p17) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (p24) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (pool_F4co) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (F4co_est) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine
timeFrame: At Day 0, 7, 14, 30 and 180
measure: 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
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Magnitude of Antigen Specific CD4+ T Cells Expressing at Least 2 Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (RT) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (Nef) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (p17) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (p24) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (pool_F4co) Specific CD4+ T Cells Expressing at Least 2 Markers/Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Frequency of Antigen (F4co_est) Specific CD4+ T Cells Expressing at Least 2 Markers/ Cytokines
timeFrame: At Day 0, 7, 14, 30 and 180
measure: Anti- RT, Nef, p17, p24 and F4co Antibody Concentrations
timeFrame: At Day 0, 7, 14, 30 and 180
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Leroux-Roels G, Bourguignon P, Willekens J, Janssens M, Clement F, Didierlaurent AM, Fissette L, Roman F, Boutriau D. Immunogenicity and safety of a booster dose of an investigational adjuvanted polyprotein HIV-1 vaccine in healthy adults and effect of administration of chloroquine. Clin Vaccine Immunol. 2014 Mar;21(3):302-11. doi: 10.1128/CVI.00617-13. Epub 2014 Jan 3.