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

NCT00972725 | Completed Phase 2 Results

• 1 other identifier: 113165
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

AIDS

Keywords

Chloroquine; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (19)

• Magnitude of Antigen Specific CD8+ T Cells Expressing at Least One Cytokine

  At Day 0, 7, 14, 30 and 180

• Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine

  At Day 0, 7, 14, 30 and 180

• Frequency of Antigen (RT) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine

  At Day 0, 7, 14, 30 and 180

• Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine

  At Day 0, 7, 14, 30 and 180

• Frequency of Antigen (Nef) Specific CD8+ T Cells Expressing at Least One Marker/ Cytokine

  At Day 0, 7, 14, 30 and 180

Study Arms (2)

GSK732461+Nivaquine Group

EXPERIMENTAL

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); Drug: Chloroquine

GSK732461 Group

ACTIVE COMPARATOR

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)

Interventions

GSK Biologicals' HIV vaccine (732461) BIOLOGICAL

1 dose intramuscular injection

GSK732461 Group; GSK732461+Nivaquine Group

Chloroquine DRUG

One dose of 300 mg

Also known as: Nivaquine®

GSK732461+Nivaquine Group

Eligibility Criteria

• Age: 18 Years - 52 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Ghent, 9000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 24391139 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 7, 2009
• Study Start: December 1, 2009
• Primary Completion: October 4, 2010
• Study Completion: October 4, 2010
• Last Updated: August 17, 2018
• Results First Posted: April 13, 2017

Record last verified: 2017-03

Locations

BE (1)