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

6. juni 2019 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

110

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 50 år (Voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Trippel

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Biologisk: GSKs kandidat Mycobacterium tuberculosis vaksine 692342
Intramuskulær injeksjon, 2 doser ved 0, 1 måned
Eksperimentell: 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.
Biologisk: GSKs kandidat Mycobacterium tuberculosis vaksine 692342
Intramuskulær injeksjon, 2 doser ved 0, 1 måned
Aktiv 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.
Biologisk: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system
Intramuscular injection, 2 doses at 0, 1 month
Aktiv 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.
Biologisk: Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Intramuscular injection, 2 doses at 0, 1 month
Placebo komparator: 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.
Biologisk: Kontrollvaksine med adjuvanssystemet.
Intramuskulær injeksjon, 2 doser ved 0, 1 måned

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: At Day 37
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
At Day 37
Levels of Immunoglobulin E
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: At Day 37
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
At Day 37

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

GlaxoSmithKline

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

15. november 2006

Primær fullføring (Faktiske)

1. desember 2009

Studiet fullført (Faktiske)

1. desember 2009

Datoer for studieregistrering

Først innsendt

9. november 2006

Først innsendt som oppfylte QC-kriteriene

9. november 2006

Først lagt ut (Anslag)

10. november 2006

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

19. juni 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. juni 2019

Sist bekreftet

1. juni 2019

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 106227
  • 106228 (Annen identifikator: GSK)
  • 108736 (Annen identifikator: GSK)
  • 108738 (Annen identifikator: GSK)
  • 2005-004497-24 (EudraCT-nummer)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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