Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults

NCT00397943 | Completed Phase 2 Results

• 5 other identifiers: 1062271062281087361087382005-004497-24
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults.

Conditions

Tuberculosis

Keywords

Tuberculosis

Outcome Measures

Primary Outcomes (24)

• Number of Subjects With Any and Grade 3 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) follow-up period after each vaccine dose and across doses

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms and headache. 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 causally related to the study vaccination.

  During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses

• Number of Subjects With Any, Grade 3 and Related 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 outside 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 (Days 0-29) follow-up period after each vaccine dose

• Number of Subjects With Serious Adverse Events (SAEs)

  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 Active Vaccination Phase (from Day 0 up to Month 2)

• Number of Subjects With SAEs

  SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From Month 2 up to Month 12

• Number of Subjects With SAEs

  SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.

  From Month 12 up to Month 24

• Number of Subjects With SAEs

  SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.

  From Month 24 up to Month 36

• Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels

  Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.

  At Day 0

• Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels

  Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.

  At Day 7

• Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels

  Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.

  At Day 30

• Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels

  Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.

  At Day 37

• Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels

  Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.

  At Day 60

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 0

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 1

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 7

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 30

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 31

• Levels of C-reactive Protein

  The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).

  At Day 37

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 0

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 1

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 7

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 30

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 31

• Levels of Immunoglobulin E

  The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).

  At Day 37

Secondary Outcomes (9)

• Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F

  At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)

• Antibody Concentrations Against M. Tuberculosis Fusion Protein M72

  At Year 2 (Month 24) and Year 3 (Month 36)

• Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines

  At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)

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

  At Year 2 (Month 24) and Year 3 (Month 36)

• Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule

  At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)

Study Arms (5)

M72/AS01B Group

EXPERIMENTAL

Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342

M72/AS02A Group

EXPERIMENTAL

Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342

Mtb72F/AS02A Group

ACTIVE COMPARATOR

Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system

Non-adjuvanted Group

ACTIVE COMPARATOR

Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Biological: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline

Control Group

PLACEBO COMPARATOR

Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.

Biological: Control vaccine with the adjuvant system.

Interventions

GSK's candidate Mycobacterium tuberculosis vaccine 692342 BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

M72/AS01B Group; M72/AS02A Group

Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Mtb72F/AS02A Group

Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Non-adjuvanted Group

Control vaccine with the adjuvant system. BIOLOGICAL

Intramuscular injection, 2 doses at 0, 1 month

Control Group

Eligibility Criteria

• Age: 18 Years - 50 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 50 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to any study procedure.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).
• Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis.
• Seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies
• If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
• No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray.

You may not qualify if:

• History of previous exposure to experimental products containing components of the experimental vaccine.
• 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.
• Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
• Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
• History of documented exposure to Mycobacterium tuberculosis.
• History of prior vaccination with experimental Mycobacterium tuberculosis vaccines.
• Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
• Participation in another experimental protocol during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition; or family history of congenital or hereditary immunodeficiency.
• History of hypersensitivity to vaccines or vaccine components
• History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
• Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease.
• History of any neurological disorders or seizures.
• History of chronic alcohol consumption and/or drug abuse.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Ghent, 9000, Belgium

Location

Related Publications (2)

• Leroux-Roels I, Forgus S, De Boever F, Clement F, Demoitie MA, Mettens P, Moris P, Ledent E, Leroux-Roels G, Ofori-Anyinam O; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial. Vaccine. 2013 Apr 19;31(17):2196-206. doi: 10.1016/j.vaccine.2012.05.035. Epub 2012 May 27.

  PMID: 22643213 BACKGROUND

• Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.

  PMID: 33493551 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: November 9, 2006
• First Posted: November 10, 2006
• Study Start: November 15, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: June 19, 2019
• Results First Posted: August 13, 2018

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)