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

NCT00707967 | Completed Phase 2 Results

• 1 other identifier: 111517
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Keywords

Tuberculosis vaccine

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (5)

• Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines

  At Day 0, 30, 60 and 210

• Frequency of M72 Specific CD4/8+ T Cells Expressing at Least One Cytokine and Another Signal Molecule

  At Day 0, 30, 60 and 210

• Cell Count of CD4+ T Cells

  At Day 0, 30, 60 and 210

• Anti-M72 Specific Antibody Concentrations

  At Day 0, 30, 60 and 210

• Number of Subjects With Significant Highly Active Anti-Retroviral Therapy (HAART) Changes

  From Day 60 to Day 210

Study Arms (3)

Group A

EXPERIMENTAL

Subjects receiving the candidate vaccine

Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342

Group B

PLACEBO COMPARATOR

Subjects receiving the adjuvant

Biological: Control vaccine with the adjuvant system.

Group C

PLACEBO COMPARATOR

Subjects receiving physiological saline

Biological: Control vaccine with physiological saline

Interventions

GSK's candidate Mycobacterium tuberculosis vaccine 692342 BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Group A

Control vaccine with the adjuvant system. BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Group B

Control vaccine with physiological saline BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Group C

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Lausanne, 1011, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 24911353 DERIVED

• 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.

  PMID: 24864125 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 1, 2008
• Study Start: June 30, 2008
• Primary Completion: May 27, 2009
• Study Completion: May 27, 2009
• Last Updated: August 24, 2018
• Results First Posted: January 6, 2017

Record last verified: 2016-11

Locations

CH (1)