Salmonella Infections
Conditions
Keywords
GVGH iNTS-GMMA vaccine, Safety, Reactogenicity, Immunogenicity, sub-Saharan Africa, African adults, children and infants, Age de-escalation, Invasive nontyphoidal Salmonella
Brief summary
The purpose of this study is to evaluate the safety, reactogenicity, and immune response of the GlaxoSmithKline (GSK) Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-generalized modules for membrane antigens (iNTS-GMMA) candidate vaccine against S. Typhimurium and S. Enteritidis with an age de-escalation and dose escalation approach in African population, starting with adults (18-50 years of age), then in children (24-59 months of age) and finally in infants (9 months and 6 weeks of age). Infants are the target for primary vaccination from 6 weeks of age.
Detailed description
The study will be conducted as follows: * Adult participants will receive either iNTS-GMMA Dose C (high) or a control vaccine intramuscularly on Day 1 and Day 57. * Child participants will receive either Dose B (medium) or Dose C (high) of the candidate vaccine or the control on Day 1 and Day 57. * Infant participants (9 months of age) will receive either Dose A (low), Dose B (medium), or Dose C (high) of the candidate vaccine or the control on Day 1, Day 85, and Day 169. * Infant participants (6 weeks of age) will receive either Dose A (low), Dose B (medium), or Dose C (high) of the candidate vaccine or the control on Day 1, Day 57 and Day 232.
Interventions
BIOLOGICALiNTS-GMMA Dose C
-2 doses of iNTS-GMMA Dose C vaccine administered intramuscularly, at Day 1 and Day 57 to adults and children in the Adults\_Dose C and Children\_Dose C groups; -3 doses of iNTS-GMMA Dose C vaccine administered intramuscularly, at Day 1, Day 85 and Day 169 to infants in the Infants\_9M\_Dose C group, and at Day 1, Day 57 and at Day 232 to infants in the Infants\_6W\_Dose C group.
BIOLOGICALiNTS-GMMA Dose B
-2 doses of iNTS-GMMA Dose B vaccine administered intramuscularly, at Day 1 and Day 57 to children in the Children\_Dose B group; -3 doses of iNTS-GMMA Dose B vaccine administered intramuscularly, at Day 1, Day 85 and Day 169 to infants in the Infants\_9M\_Dose B group, and at Day 1, Day 57 and Day at 232 to infants in the Infants\_6W\_Dose B group.
BIOLOGICALiNTS-GMMA Dose A
3 doses of iNTS-GMMA Dose A vaccine administered intramuscularly, at Day 1, Day 85 and Day 169 to infants in the Infants\_9M\_Dose A group, and at Day 1, Day 57 and Day at 232 to infants in the Infants\_6W\_Dose A group.
BIOLOGICALMenACWY
-1 dose of MenACWY vaccine administered intramuscularly at Day 1 to adults in the Adults\_Control group; -2 doses of MenACWY vaccine administered intramuscularly at Day 1 and Day 57 to children in the Children\_Control B and Children\_Control C groups, and at Day 1 and Day 85 to infants in the Infants\_9M\_Control A, Infants\_9M\_Control B and Infants\_9M\_Control C groups; -3 doses of MenACWY vaccine administered intramuscularly at Day 1, Day 57 and at Day 232 to infants in the Infants\_6W\_Control A, Infants\_6W\_Control B and Infants\_6W\_Control C groups. A 4th dose of MenACWY vaccine is administered after the trial ends, to infants in the aforementioned study groups, as per the licensed indication and in private vaccination settings.
COMBINATION_PRODUCTDTPa-HBV-IPV+Hib
1 dose of DTPa-HBV-IPV+Hib vaccine administered intramuscularly at Day 169 to infants in the Infants\_9M\_Control A, Infants\_9M\_Control B and Infants\_9M\_Control C groups.
DRUGPlacebo
1 dose of Placebo administered intramuscularly at Day 57 to adults in the Adults\_Control group.
BIOLOGICALMeasles and Rubella vaccine
Measles and Rubella vaccine is administered to study participants, as part of an Expanded Program on Immunization (EPI) vaccination at the local EPI vaccination centers, and not part of the current clinical trial, as follows: - at 28 days after the first study intervention administration (occurring at Day 1) to infants in the Infants\_9M\_Dose A, Infants\_9M\_Control A, Infants\_9M\_Dose B, Infants\_9M\_Control B, Infants\_9M\_Dose C and Infants\_9M\_Control C groups. - at 28 days after the third study intervention administration (occurring at Day 232) to infants in Infants\_6W\_Dose A, Infants\_6W\_Control A, Infants\_6W\_Dose B, Infants\_6W\_Control B, Infants\_6W\_Dose C and Infants\_6W\_Control C groups.
BIOLOGICALYellow Fever vaccine
Yellow Fever vaccine is administered to study participants, as part of an Expanded Program on Immunization (EPI) vaccination at the local EPI vaccination centers, and not part of the current clinical trial, as follows: - at 28 days after the first study intervention administration (occurring at Day 1) to infants in the Infants\_9M\_Dose A, Infants\_9M\_Control A, Infants\_9M\_Dose B, Infants\_9M\_Control B, Infants\_9M\_Dose C and Infants\_9M\_Control C groups. - at 28 days after the third study intervention administration (occurring at Day 232) to infants in Infants\_6W\_Dose A, Infants\_6W\_Control A, Infants\_6W\_Dose B, Infants\_6W\_Control B, Infants\_6W\_Dose C and Infants\_6W\_Control C groups.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data will be collected in an observer-blind manner.
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 50 Years
Healthy volunteers
Yes
Inclusion criteria
All participants (adults, children, infants at 9 months of age and infants at 6 weeks of age) will be enrolled in the clinical site in Ghana and must satisfy ALL the following criteria at study entry: * Participants and/or participants' parent(s)/Legally Acceptable Representative(s) (LAR), who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits). * Written or witnessed/thumb printed informed consent obtained from the participant/parent(s)/LAR(s) of the participant prior to performance of any study-specific procedure. * Healthy participants as established by medical history, clinical examination, and laboratory investigations. * Participants satisfying screening requirements. * Participants negative for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. Adult participants must satisfy ALL the following criteria in the study entry: * A male or female between and including 18 and 50 years of age at the time of the first study intervention administration. * Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. * Female participants of childbearing potential may be enrolled in the study, if the participant: * has practiced adequate contraception for 1 month prior to the study intervention administration, and * has a negative pregnancy test on the day of study intervention administration, and * has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series. The Ghana card will be used as source document to verify the ages for the adults. Child participants must satisfy ALL the following criteria at study entry: * A male or female between and including 24 and 59 months of age at the time of the first study intervention administration. * Previously completed routine childhood vaccinations to the best knowledge of the participant's parent(s)/LAR's. * Born after a gestation period of ≥37 weeks. Infant participants must satisfy ALL the following criteria at study entry: * A male or female 6 weeks or 9 months of age at the time of the first study intervention administration. * Born after a gestation period of ≥37 weeks. * Born to a mother seronegative for HIV, hepatitis B virus and hepatitis C virus. The Road to Health Chart will be used as source document to confirm the ages for the children and infants.
Exclusion criteria
Medical conditions * Known exposure to S. Typhimurium or S. Enteritidis during the period starting at birth for infants and children, and at 3 years for adults, as documented by patient records * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions. * Hypersensitivity, including allergy, to medicinal products or medical equipment whose use is foreseen in this study. * Progressive, unstable, or uncontrolled clinical conditions. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination * Major congenital defects, as assessed by the investigator. * Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests. * Acute disease and/or fever at the time of enrollment (fever is defined as temperature ≥ 38.0°C). * Recurrent history or uncontrolled neurological disorders or seizures. * Any clinically significant hematological and/or biochemical laboratory abnormality. * Undernutrition defined as World Health Organization (WHO) Z-score less than -2 standard deviation (SD). * Malaria infection defined as the presence of asexual parasites in the blood. * Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. * Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the study. * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant therapy * History of receiving any investigational iNTS or GMMA vaccines in the participant's life. * Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days before the first dose of study interventions, or their planned use during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 14 days before each dose and ending 28 days after the last dose of study interventions administration, with the exception of flu vaccines and vaccines administered as part of a public health vaccination campaign. * A vaccine not foreseen by the study protocol administered during the period starting at 14 days before the first dose and ending 14 days after the last dose of study interventions administration for live vaccines or 7 days in case of inactivated vaccines\*, with the exception of flu vaccines or COVID-19 vaccine which may be considered on a case-by-case basis. * If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced if, provided it is used according to the local governmental recommendations and Sponsor is notified. Under such circumstances, a participant may be considered eligible for study enrollment and/or study intervention administration after the appropriate window for delay has passed and inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adult participants 18-50 years of age with solicited administration site events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited administration site events are pain, redness and swelling. |
| Number of adult participants 18-50 years of age with solicited systemic events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited systemic events are fever, headache, myalgia, arthralgia and fatigue. Fever is defined as axillary temperature higher than or equal to (\>=) 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). |
| Number of adult participants 18-50 years of age with unsolicited adverse events (AEs) | During 28 days after the first study intervention administration occurring at Day 1 | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. |
| Number of adult participants 18-50 years of age with serious adverse events (SAEs) | From first study intervention administration (Day 1) up to the end of study participation (Day 85) | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or results in abnormal pregnancy outcomes. |
| Number of adult participants 18-50 years of age with adverse events (AEs) leading to withdrawal from the study or discontinuation of study intervention | From first study intervention administration (Day 1) up to the end of study participation (Day 85) | An AE is any untoward medical occurrence (an unfavorable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention. Any AEs that lead to discontinuation of study intervention and/or the study are considered under this outcome measure. |
| Number of adult participants 18-50 years of age with deviations from reference ranges or baseline values for hematological, renal and hepatic panel test results | At Day 8 (7 days after the first study intervention administration) | Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Number of child participants 24-59 months of age with solicited administration site events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited administration site events are pain, redness and swelling. |
| Number of child participants 24-59 months of age with solicited systemic events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited systemic events are fever, irritability/fussiness, loss of appetite, drowsiness and vomiting. Fever is defined as axillary temperature \>= 38.0 °C/100.4 degrees °F. |
| Number of child participants 24-59 months of age with unsolicited AEs | During 28 days after the first study intervention administration occurring at Day 1 | — |
| Number of child participants 24-59 months of age with serious adverse events (SAEs) | From first study intervention administration (Day 1) up to the end of study participation (Day 85) | — |
| Number of child participants 24-59 months of age with AEs leading to withdrawal from the study or discontinuation of study intervention | From first study intervention administration (Day 1) up to the end of study participation (Day 85) | — |
| Number of child participants 24-59 months of age with deviations from reference ranges or baseline values for hematological, renal and hepatic panel test results | At Day 8 (7 days after the first study intervention administration) | — |
| Number of infant participants 9 months of age with solicited administration site events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited administration site events are pain, redness and swelling. |
| Number of infant participants 9 months of age with solicited systemic events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited systemic events are fever, irritability/fussiness, loss of appetite, drowsiness, and vomiting. Fever is defined as axillary temperature \>= 38.0 °C/100.4 degrees °F. |
| Number of infant participants 9 months of age with unsolicited adverse events (AEs) | During 28 days after the first study intervention administration occurring at Day 1 | — |
| Number of infant participants 9 months of age with serious adverse events (SAEs) | From first study intervention administration (Day 1) up to the end of study participation (Day 337) | — |
| Number of infant participants 9 months of age with adverse events (AEs) leading to withdrawal from the study or discontinuation of study intervention | From first study intervention administration (Day 1) up to the end of study participation (Day 337) | — |
| Number of infant participants 9 months of age with deviations from reference range or baseline values for hematological, renal and hepatic panel test results | At Day 8 (7 days after the first study intervention administration) | — |
| Number of infant participants 6 weeks of age with solicited administration site events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited administration site events are pain, redness and swelling. |
| Number of infant participants 6 weeks of age with solicited systemic events | During 7 days after the first study intervention administration occurring at Day 1 | The solicited systemic events are fever, irritability/fussiness, loss of appetite, drowsiness, and vomiting. Fever is defined as axillary temperature \>= 38.0 °C/100.4 degrees °F. |
| Number of infant participants 6 weeks of age with unsolicited adverse events (AEs) | During 28 days after the first study intervention administration occurring at Day 1 | — |
| Number of infant participants 6 weeks of age with SAEs | From first study intervention administration (Day 1) up to 28 days after second study intervention (Day 85) | — |
| Number of infant participants 6 weeks of age with adverse events (AEs) leading to MR-VAC administration withdrawal from the study or discontinuation of study intervention | From first study intervention administration (Day 1) up to 28 days after second study intervention (Day 85) | — |
| Number of infant participants 6 weeks of age with deviations from reference ranges or baseline values for hematological, renal, and hepatic panel test results | At Day 8 (7 days after the first study intervention administration) | — |
| Number of infant participants 6 weeks of age with deviations from reference ranges or baseline values for hematological, renal, and hepatic panel test results at Day 64 | At Day 64 (7 days after the second study intervention administration) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of infant participants 6 weeks of age with solicited administration site events | During 7 days after the third study intervention administration occurring at Day 232 | The solicited administration site events are pain, redness and swelling. |
| Number of infant participants 6 weeks of age with solicited systemic events | During 7 days after the third study intervention administration occurring at Day 232 | The solicited systemic events are fever, irritability/fussiness, loss of appetite, drowsiness, and vomiting. Fever is defined as axillary temperature \>= 38.0 °C/100.4 degrees °F. |
| Number of infant participants 6 weeks of age with unsolicited AEs | During 28 days after the third study intervention administration occurring at Day 232 | — |
| Number of infant participants 6 weeks of age with SAEs | From 28 days after the second study intervention administration (Day 85) up to end of study participation (Day 400) | — |
| Number of infant participants 6 weeks of age with adverse events (AEs) leading to withdrawal from the study or withholding further study intervention administration | From 28 days after the second study intervention administration (Day 85) up to end of study participation (Day 400) | — |
| Number of infant participants 6 weeks of age with deviations from reference ranges or baseline values for hematological, renal, and hepatic panel test results | At Day 239 (7 days after the study intervention administration) | — |
| Anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in adult participants 18-50 years of age | At Days 1 and 57 (before each study intervention administration) and at Days 29 and 85 (28 days after each study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG GMCs are assessed. |
| Anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in child participants 24-59 months of age | At Days 1 and 57 (before each study intervention administration) and at Days 29 and 85 (28 days after each study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG GMCs are assessed. |
| Anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in infant participants 9 months of age | At Days 1, 85 and 169 (before each study intervention administration) and at Days 29, 113 and 197 (28 days after each study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG GMCs are assessed. |
| Anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in infant participants 6 weeks of age | At Days 1, 57 and 232 (before each study intervention administration) at Days 29, 85 and 260 (28 days after each study intervention administration) and at Day 239 (7 days after the third study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG GMCs are assessed. |
| Number of adult participants 18-50 years of age achieving, for each antigen (Ag), at least a 2-fold and 4-fold rise in anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) antibody concentration | At Days 29 and 85 (28 days after each study intervention administration) compared to Day 1 (baseline, prior to first study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG antibody concentrations are assessed. |
| Number of child participants 24-59 months of age achieving, for each antigen (Ag), at least a 2-fold and 4-fold rise in anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) antibody concentration | At Days 29 and 85 (28 days after each study intervention administration) compared to Day 1 (baseline, prior to first study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG antibody concentrations are assessed. |
| Number of infant participants 9 months of age achieving, for each antigen (Ag), at least a 2-fold and 4-fold rise in anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) antibody concentration | At Days 29, 113 and 197 (28 days after each study intervention administration) compared to Day 1 (baseline, prior to first study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG antibody concentrations are assessed. |
| Number of infant participants 6 weeks of age achieving, for each antigen (Ag), at least a 2-fold and 4-fold rise in anti-invasive nontyphoidal Salmonella (iNTS) serotype specific immunoglobulin G (IgG) antibody concentration | At Days 29, 85 and 260 (28 days after each study intervention administration) and at Day 239 (7 days after the third study intervention administration) compared to Day 1 (baseline, prior to first study intervention administration) | Anti-S. Typhimurium OAg total IgG and anti-S. Enteritidis OAg total IgG antibody concentrations are assessed. |
Countries
Ghana
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed