Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in HIV-positive Adults.

Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine (692342) in HIV-positive Adults.

This study will assess the safety and immunogenicity of a GSK Biologicals' candidate TB vaccine (692342) administered at 0, 1 month to HIV-positive adults living in Switzerland.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342; Biological: Control vaccine with the adjuvant system.; Biological: Control vaccine with physiological saline

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1011
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the Investigator believes that they can and will comply with the requirements of the protocol.
• A male or female between, and including, 18 and 50 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to any study procedure.

• Subjects must be HIV-positive and must have:

  • received Highly Active Antiretroviral therapy for a minimum of 12 consecutive months prior to screening
  • documented suppressed HIV-1 RNA levels following HAART-treatment.
  • a protocol defined CD4+ T cell count at screening
• If the subject is female, she must be of non-childbearing potential, or she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of vaccination.
• Clinically acceptable laboratory values prior to randomisation as determined by the Investigator.
• No evidence of TB disease with no pulmonary pathology as confirmed by chest X-ray.
• No history of extrapulmonary TB.
• No history of chemotherapy for TB.

Exclusion Criteria:

• Any change in antiretroviral drug regimen within 12 weeks prior to screening.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Administration of a registered live vaccine not foreseen by the study within 30 days preceding the first dose of study vaccine and administration of a registered inactivated vaccine within 14 days preceding the first dose of study vaccine.
• History of previous administration of experimental Mycobacterium tuberculosis vaccines.
• History of previous exposure to experimental products containing components of the experimental vaccine.
• Chronic administration of immunosuppressive or other immune-modifying drugs within six months prior to the first vaccine dose.
• Administration of any immunoglobulins, any immunotherapy and/or any blood products within the three months preceding the first dose of study vaccination, or planned administrations during the study period.
• Any condition or illness (acute, chronic or history) or medication, which in the opinion of the Investigator might interfere with the evaluation of the safety or immunogenicity of the vaccine.
• Planned participation or participation in another experimental protocol during the study period.
• A family history of congenital or hereditary immunodeficiency. •Any chronic drug therapy, other than HAART or prophylaxis for opportunistic HIV-related infections to be continued during the study period. Vitamins and/or dietary supplements, birth control pills, anti-histamines for seasonal allergies and SSRIs are allowed.
• Subjects taking any of the following medication: systemic steroids, interleukins, systemic interferons or systemic chemotherapy.
• History of allergic reactions or anaphylaxis to any vaccine.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of chronic alcohol consumption and/or drug abuse which in the Investigator's opinion would put the subject at risk.
• Pregnant female, lactating female or female planning to become pregnant or stop contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Subjects receiving the candidate vaccine	Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342; Intramuscular injection, 2 doses at 0, 1 month
PLACEBO_COMPARATOR: Group B; Subjects receiving the adjuvant	Biological: Control vaccine with the adjuvant system.; Intramuscular injection, 2 doses at 0, 1 month
PLACEBO_COMPARATOR: Group C; Subjects receiving physiological saline	Biological: Control vaccine with physiological saline; Intramuscular injection, 2 doses at 0, 1 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. Relationship analysis was not performed.	During the 7-day period (Days 0-6) post vaccination following each dose
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 (gastro) [nausea, vomiting, diarrhoea and/or abdominal pain], headache, malaise and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day period (Days 0-6) post vaccination following each dose
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 30-day period (Days 0-29) post vaccination
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 210
Number of Subjects With Normal Biochemical and Haematological Levels	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Normal Haematological Levels	Among biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Normal Haematological Levels	Among biochemical and haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Biochemical and Haematological Levels Below Normal	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Below Normal	Among biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Below Normal	Among biochemical and haematological parameters assessed were [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Biochemical and Haematological Levels Above Normal	Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Above Normal	Among biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60
Number of Subjects With Haematological Levels Above Normal	Among biochemical and haematological parameters assessed were [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above.	At Day 0, 7, 30, 37 and 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines	Among cytokines expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).	At Day 0, 30, 60 and 210
Frequency of M72 Specific CD4/8+ T Cells Expressing at Least One Cytokine and Another Signal Molecule	Expressed cytokine combinations for CD4+ T cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ. For CD8+ T cells no vaccine induced responses were observed, thus results are presented only for the frequency of M72-specific CD8+ T cells expressing at least two cytokines.	At Day 0, 30, 60 and 210
Cell Count of CD4+ T Cells	CD4+ T cell counts are defined by values greater than (>) 200 cells per cubic millimeters (mm3) at screening for enrolment into the study.	At Day 0, 30, 60 and 210
Anti-M72 Specific Antibody Concentrations	Concentrations given in Enzyme-Linked Immunosorbent Assay units per milliliter (EL.U/mL) were expressed in Geometric Mean Concentrations (GMCs).	At Day 0, 30, 60 and 210
Number of Subjects With Significant Highly Active Anti-Retroviral Therapy (HAART) Changes	Recorded significant HAART change refers to one subject switching the Combivir drug to Truvada as planned by personal physician, with no relationship to vaccination, prior to study enrolment.	From Day 60 to Day 210

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Thacher EG, Cavassini M, Audran R, Thierry AC, Bollaerts A, Cohen J, Demoitie MA, Ejigu D, Mettens P, Moris P, Ofori-Anyinam O, Spertini F. Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial. AIDS. 2014 Jul 31;28(12):1769-81. doi: 10.1097/QAD.0000000000000343.
• Roy-Ghanta S, Van der Most R, Li P, Vaughn DW. Responses to A(H1N1)pdm09 influenza vaccines in participants previously vaccinated with seasonal influenza vaccine: a randomized, observer-blind, controlled study. J Infect Dis. 2014 Nov 1;210(9):1419-30. doi: 10.1093/infdis/jiu284. Epub 2014 May 26.

Study record dates

Study Major Dates

• Study Start: June 30, 2008
• Primary Completion (ACTUAL): May 27, 2009
• Study Completion (ACTUAL): May 27, 2009

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: June 27, 2008
• First Posted (ESTIMATE): July 1, 2008

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Tuberculosis vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 111517