Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Human Immunodeficiency Virus (HIV)-Positive Adults

NCT01262976 | Completed Phase 2 Results

• 1 other identifier: 113935
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the safety and immunogenicity of a GlaxoSmithKline (GSK) Biologicals' candidate tuberculosis vaccine (692342) administered to Human Immunodeficiency Virus (HIV)-positive adults aged 18 to 59 years, living in a tuberculosis endemic region. Subjects will be followed-up for 3 years. Subjects will be enrolled in 3 cohorts:

• HIV-positive adults on highly active antiretroviral therapy
• HIV-positive adults not on highly active antiretroviral therapy
• HIV-negative adults Each cohort will have 2 groups.

Conditions

Tuberculosis

Keywords

Tuberculosis vaccine

Outcome Measures

Primary Outcomes (9)

• Number of Subjects With Grade 3 Solicited Local Symptoms

  Solicited local symptoms assessed were pain and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 50 millimeters (mm) of injection site.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Grade 3 Solicited General Symptoms

  Solicited general symptoms assessed 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. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C.

  During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Grade 3 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. Grade 3 AE = an AE which prevented normal, everyday activities.

  During the 30-day (Days 0-29) post-vaccination 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.

  From screening up to one month post Dose 2

• Number of Subjects With Grade 3 and Grade 4 Haematological and Biochemical Levels

  Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  At Day 0

• Number of Subjects With Grade 3 and 4 Haematological and Biochemical Levels

  Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  At Day 7

• Number of Subjects With Grade 3 and Grade 4 Haematological/Biochemical Levels

  Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  At Day 30

• Number of Subjects With Grade 3-4 Haematological and Biochemical Levels

  Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  At Day 37

• Number of Subjects With Grade 3-4 Haematological/Biochemical Levels

  Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  At Day 60

Secondary Outcomes (15)

• Anti-Mycobacterium Tuberculosis Fusion Protein (M72) Specific Antibody Concentrations

  At Days 0, 30, 60, 210 and at Years 1, 2 and 3

• Number of Seroconverted Subjects for M72-specific Antibodies

  At Days 0, 30, 60, 210 and at Years 1, 2 and 3

• Frequency of M72-cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Immune Markers

  At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3

• Frequency of M72-CD4+ T-cells Expressing Any Combination of Cytokines

  At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3

• M72-cluster of Differentiation 4 (CD4+) T-cells Frequency Expressing Any Combination of Cytokines

  At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3

Study Arms (6)

HIV(+)-HA/GSK692342

EXPERIMENTAL

HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: GSK's investigational vaccine 692342

HIV(+)-HA/Placebo

PLACEBO COMPARATOR

HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: Physiological saline

HIV(+)-TN/GSK692342

EXPERIMENTAL

HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: GSK's investigational vaccine 692342

HIV(+)-TN/Placebo

PLACEBO COMPARATOR

HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: Physiological saline

HIV(-)/GSK692342

EXPERIMENTAL

Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: GSK's investigational vaccine 692342

HIV(-)/Placebo

PLACEBO COMPARATOR

Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.

Biological: Physiological saline

Interventions

GSK's investigational vaccine 692342 BIOLOGICAL

Intramuscular, 2 doses

HIV(+)-HA/GSK692342; HIV(+)-TN/GSK692342; HIV(-)/GSK692342

Physiological saline BIOLOGICAL

Intramuscular, 2 doses

HIV(+)-HA/Placebo; HIV(+)-TN/Placebo; HIV(-)/Placebo

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• 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 59 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to any study procedure.
• 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,
• has a negative pregnancy test on the day of vaccination, and
• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
• Clinically acceptable laboratory values at screening as determined by the investigator.
• No evidence of tuberculosis disease with no evidence of pulmonary pathology as confirmed by chest X-ray.
• No history of extra pulmonary tuberculosis.
• Based on their medical history, all subjects must have no history of chemotherapy for tuberculosis.
• Subjects must be HIV-positive and under care of a physician for at least 6 months.
• Subjects must have a CD4+T cell count \>= 250 cells/mm3 at screening.
• Subjects must be stable on highly active antiretroviral therapy for at least 6 months, with an undetectable HIV viral load level at screening.

You may not qualify if:

• Use of any investigational or non-registered product 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 Mtb vaccines.
• History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine
• Chronic administration of immunosuppressant or other immune-modifying drugs within six months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone \>= 20 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
• Any condition or illness 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 with an experimental product during the study period.
• Administration of any immunoglobulin, 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.
• Subjects taking any of the following medication: chronic administration of systemic steroids, interleukins, systemic interferon or systemic chemotherapy.
• History of allergic reactions or anaphylaxis to any drug or 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.
• Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests.
• Any change in anti-retroviral drug regimen within 12 weeks prior to screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Tharamani Chennai, 600113, India

Location

Related Publications (1)

• Kumarasamy N, Poongulali S, Beulah FE, Akite EJ, Ayuk LN, Bollaerts A, Demoitie MA, Jongert E, Ofori-Anyinam O, Van Der Meeren O. Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial. Medicine (Baltimore). 2018 Nov;97(45):e13120. doi: 10.1097/MD.0000000000013120.

  PMID: 30407329 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 20, 2010
• Study Start: January 17, 2011
• Primary Completion: July 17, 2012
• Study Completion: June 4, 2015
• Last Updated: September 17, 2018
• Results First Posted: September 17, 2018

Record last verified: 2017-11

Locations

IN (1)