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

6 czerwca 2019 zaktualizowane przez: GlaxoSmithKline

Safety, Reactogenicity & Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Administered Intramuscularly According to a Schedule of 0, 1 Month, to Healthy Adults Aged 18 to 50 Years

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

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

The study is designed to have a vaccination phase (includes screening, 2 doses of vaccine 1 month apart and follow-up until 1 month post dose 2), which will be performed in an observer blinded manner. This will be followed by 3 years of follow-up which will continue in an open manner.

No new subjects will be recruited at the follow-up phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

110

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Belgia
      • Gent, Belgia, 9000
        • GSK Investigational Site

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 50 lat (Dorosły)

Akceptuje zdrowych ochotników

Tak

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.
  • 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.

Exclusion Criteria:

  • 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.
  • Major congenital defects.
  • Pregnant female, lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Zapobieganie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Potroić

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: M72/AS01B Group
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.
Biologiczny: Kandydat GSK na szczepionkę Mycobacterium tuberculosis 692342
Wstrzyknięcie domięśniowe, 2 dawki w 0, 1 miesiącu
Eksperymentalny: M72/AS02A Group
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.
Biologiczny: Kandydat GSK na szczepionkę Mycobacterium tuberculosis 692342
Wstrzyknięcie domięśniowe, 2 dawki w 0, 1 miesiącu
Aktywny komparator: Mtb72F/AS02A Group
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.
Biologiczny: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system
Intramuscular injection, 2 doses at 0, 1 month
Aktywny komparator: Non-adjuvanted Group
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.
Biologiczny: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Intramuscular injection, 2 doses at 0, 1 month
Komparator placebo: Control Group
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.
Biologiczny: Szczepionka kontrolna z systemem adiuwantowym.
Wstrzyknięcie domięśniowe, 2 dawki w 0, 1 miesiącu

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Ramy czasowe: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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
Ramy czasowe: During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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)
Ramy czasowe: During the 30-day (Days 0-29) follow-up period after each vaccine dose
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)
Ramy czasowe: During the Active Vaccination Phase (from Day 0 up to Month 2)
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
Ramy czasowe: From Month 2 up to Month 12
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
Ramy czasowe: From Month 12 up to Month 24
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
Ramy czasowe: From Month 24 up to Month 36
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
Ramy czasowe: At Day 0
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
Ramy czasowe: At Day 7
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
Ramy czasowe: At Day 30
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
Ramy czasowe: At Day 37
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
Ramy czasowe: At Day 60
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
Ramy czasowe: At Day 0
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 0
Levels of C-reactive Protein
Ramy czasowe: At Day 1
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 1
Levels of C-reactive Protein
Ramy czasowe: At Day 7
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 7
Levels of C-reactive Protein
Ramy czasowe: At Day 30
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 30
Levels of C-reactive Protein
Ramy czasowe: At Day 31
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 31
Levels of C-reactive Protein
Ramy czasowe: At Day 37
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 37
Levels of Immunoglobulin E
Ramy czasowe: At Day 0
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 0
Levels of Immunoglobulin E
Ramy czasowe: At Day 1
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 1
Levels of Immunoglobulin E
Ramy czasowe: At Day 7
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 7
Levels of Immunoglobulin E
Ramy czasowe: At Day 30
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 30
Levels of Immunoglobulin E
Ramy czasowe: At Day 31
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 31
Levels of Immunoglobulin E
Ramy czasowe: At Day 37
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 37

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Ramy czasowe: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The reference seropositivity cut-off values for anti-M72 and anti-Mtb72F antibodies were ≥ 2.8 EU/mL and ≥ 1.0 EU/mL, respectively.
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
Ramy czasowe: At Year 2 (Month 24) and Year 3 (Month 36)
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EU/mL). The reference seropositivity cut-off value for anti-M72 antibodies was ≥ 2.8 EU/mL.
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
Ramy czasowe: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs). Note: No vaccine induced responses were observed for CD8+ T-cells, so no results are presented throughout the record.
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
Ramy czasowe: At Year 2 (Month 24) and Year 3 (Month 36)
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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
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
Ramy czasowe: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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.
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Ramy czasowe: At Year 2 (Month 24) and Year 3 (Month 36)
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.
At Year 2 (Month 24) and Year 3 (Month 36)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Ramy czasowe: At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Ramy czasowe: At Year 2 (Month 24) and Year 3 (Month 36)
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
At Year 2 (Month 24) and Year 3 (Month 36)
Concentrations of IFN-γ Produced in Serum Samples
Ramy czasowe: Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination
Concentrations are presented as geometric mean concentrations (GMCs), expressed in picogram per milliliter (pg/mL). The reference seropositivity cut-off value was equal to or above (≥) 1 pg/mL.
Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

GlaxoSmithKline

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

15 listopada 2006

Zakończenie podstawowe (Rzeczywisty)

1 grudnia 2009

Ukończenie studiów (Rzeczywisty)

1 grudnia 2009

Daty rejestracji na studia

Pierwszy przesłany

9 listopada 2006

Pierwszy przesłany, który spełnia kryteria kontroli jakości

9 listopada 2006

Pierwszy wysłany (Oszacować)

10 listopada 2006

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

19 czerwca 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

6 czerwca 2019

Ostatnia weryfikacja

1 czerwca 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 106227
  • 106228 (Inny identyfikator: GSK)
  • 108736 (Inny identyfikator: GSK)
  • 108738 (Inny identyfikator: GSK)
  • 2005-004497-24 (Numer EudraCT)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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