Clinical trial NCT05480800: A Study to Evaluate Safety, Reactogenicity, and Immune Response of GVGH iNTS-TCV Vaccine Against Invasive Nontyphoidal Salmonella and Typhoid Fever
Official title: A Phase 1/2a, Observer-blind, Randomized, Controlled, Two-stage, Multi-country Study to Evaluate the Safety, Reactogenicity, and Immune Response of the Trivalent Vaccine Against Invasive Nontyphoidal Salmonella (iNTS) and Typhoid Fever in Healthy European and African Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Salmonella Infections
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
name: Wellcome Trust
name: Global Antimicrobial Resistance Innovation Fund-(GAMRIF)
name: Bill and Melinda Gates Foundation
First posted: 2022-07-29
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety, reactogenicity, and immune response induced by the GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-typhoid conjugate (iNTS-TCV) candidate vaccine to be administered for the first time in humans. The study intervention will be evaluated in European adults in Stage 1 (a 2-step staggered design) followed by African adults in Stage 2.


Eligibility criteria: Inclusion criteria

* Participants, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
* Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
* Healthy participants as established by medical history, clinical examination, and laboratory assessment.
* Participant satisfying screening requirements.
* 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 nonchildbearing potential may be enrolled in the study. Nonchildbearing 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 trial if the participant:
* Has practiced adequate contraception for 1 month prior to 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.
* Blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the Investigator to confirm non-reproductive potential according to local laboratory reference range.
* Genetic testing for HLA-B27 will be performed at Screening and only participants with a negative result will be allowed to participate in the study\*.

  * Only for Stage 1.
* For Malawi (Stage 2), the participant lives in Blantyre and has agreed to remain in Blantyre for the study duration.

Exclusion criteria Medical Conditions

* Known exposure to S. Typhi and nontyphoidal Salmonella confirmed by blood culture during the period starting 3 years prior to first study intervention administration confirmed using past medical history.
* History of any reaction or hypersensitivity associated with any component of the study interventions.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Recurrent history or uncontrolled neurological disorders or seizures.
* Any clinically significant\* hematological and/or biochemical laboratory abnormality.

  * The Investigator should use his/her clinical judgment to decide which abnormalities are clinically significant from the panel of tests in the list of safety assays.
* Clinical conditions representing a contraindication to IM injections and/or 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.
* Confirmed positive COVID-19 polymerase chain reaction or lateral flow test during the period starting 28 days before the first administration of study vaccines (Day -28 to Day 1).
* Acute or chronic illness which may be severe enough to preclude participation.
* Any other clinical condition that, in the opinion of the Investigator, might pose additional risk to the participant due to participation in the study.
* All medical conditions will be assessed by the Investigator who may use his/her discretion to decide if the participant meets the exclusion criteria.

Prior/Concomitant Therapy

* History of receiving any typhoid vaccine (Ty21a, Vi capsular polysaccharide, or TCV) in the participant's life.
* 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 (Days -30 to 1) before the first dose of study interventions, or their planned use during the study period.
* A vaccine not foreseen by the study protocol administered during the period starting at 14 days before the first dose and ending 28 days after the last dose of study interventions administration\*, with the exception of flu vaccines or COVID-19 vaccine.

  * In case emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

When regulations allow, the recommended time intervals for administration of these vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after in case of live vaccines) each dose of study intervention administration.

* Administration of long-acting immune-modifying drugs at any time during the study period (eg, infliximab).
* Administration of Ig and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study interventions or planned administration during the study period.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune modifying drugs during the period starting 3 months prior to the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical steroids are allowed.

Prior/Concurrent Clinical Study Experience

- Concurrently participating in another clinical trial, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (vaccine and drug).

Other Exclusions

* Pregnant or lactating female
* Female planning to become pregnant or planning to discontinue contraceptive precautions
* History of/current chronic alcohol consumption and/or drug abuse. This will be decided at the discretion of the Investigator. Chronic alcohol consumption is defined as one or more of the following:
* A prolonged period of frequent and heavy alcohol use
* The inability to control drinking once it has begun
* Physical dependence manifested by withdrawal symptoms when the individual stops using alcohol
* Tolerance or the need to use increasing amounts of alcohol to achieve the same effects
* A variety of social and/or legal problems arising from alcohol use.
* Any study personnel or their immediate dependents, family, or household members.

Primary outcomes:
measure: Number of participants in Europe/Stage 1 with solicited administration site events after the first study intervention administration
timeFrame: During 7 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Europe/Stage 1 with solicited administration site events after the second study intervention administration
timeFrame: During 7 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Europe/Stage 1 with solicited administration site events after the third study intervention administration
timeFrame: During 7 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Europe/Stage 1 with solicited systemic events after the first study intervention administration
timeFrame: During 7 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Europe/Stage 1 with solicited systemic events after the second study intervention administration
timeFrame: During 7 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Europe/Stage 1 with solicited systemic events after the third study intervention administration
timeFrame: During 7 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the first study intervention administration
timeFrame: During 28 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the second study intervention administration
timeFrame: During 28 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the third study intervention administration
timeFrame: During 28 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Europe/Stage 1 with serious adverse events (SAEs)
timeFrame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
measure: Number of participants in Europe/Stage 1 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention
timeFrame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 8
timeFrame: At Day 8 (7 days after the first study intervention administration)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 64
timeFrame: At Day 64 (7 days after the second study intervention administration)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 176
timeFrame: At Day 176 (7 days after the third study intervention administration)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 29
timeFrame: At Day 29 (28 days after the first study intervention administration)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 85
timeFrame: At Day 85 (28 days after the second study intervention administration)
measure: Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 197
timeFrame: At Day 197 (28 days after the third study intervention administration)
measure: Number of participants in Africa/Stage 2 with solicited administration site events after the first study intervention administration
timeFrame: During 7 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Africa/Stage 2 with solicited administration site events after the second study intervention administration
timeFrame: During 7 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Africa/Stage 2 with solicited administration site events after the third study intervention administration
timeFrame: During 7 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Africa/Stage 2 with solicited systemic events after the first study intervention administration
timeFrame: During 7 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Africa/Stage 2 with solicited systemic events after the second study intervention administration
timeFrame: During 7 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Africa/Stage 2 with solicited systemic events after the third study intervention administration
timeFrame: During 7 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the first study intervention administration
timeFrame: During 28 days after the first study intervention administration occurring at Day 1
measure: Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the second study intervention administration
timeFrame: During 28 days after the second study intervention administration occurring at Day 57
measure: Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the third study intervention administration
timeFrame: During 28 days after the third study intervention administration occurring at Day 169
measure: Number of participants in Africa/Stage 2 with serious adverse events (SAEs)
timeFrame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
measure: Number of participants in Africa/Stage 2 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention
timeFrame: From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 8
timeFrame: At Day 8 (7 days after the first study intervention administration)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 64
timeFrame: At Day 64 (7 days after the second study intervention administration)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 176
timeFrame: At Day 176 (7 days after the third study intervention administration)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 29
timeFrame: At Day 29 (28 days after the first study intervention administration)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 85
timeFrame: At Day 85 (28 days after the second study intervention administration)
measure: Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 197
timeFrame: At Day 197 (28 days after the third study intervention administration)
Secondary outcomes:
measure: Number of participants with serious adverse events (SAEs)
timeFrame: From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
measure: Number of participants with AEs/SAEs leading to withdrawal from the study
timeFrame: From 28 days after third study intervention administration (Day 197) up to Day 337
measure: Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Europe/Stage 1, and between-group ratios
timeFrame: At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)
measure: Anti-serotype specific immunoglobulin G (IgG) within-participant geometric mean ratios (GMRs) in participants in Europe/Stage 1
timeFrame: At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)
measure: Number of participants in Europe/Stage 1 achieving, for each antigen (Ag), at least a 4-fold rise in anti-serotype specific immunoglobulin G (IgG) antibody concentration
timeFrame: At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
measure: Number of participants in Europe/Stage 1 with Anti-S. typhi Vi Ag IgG antibody concentrations equivalent to ≥ 4.3 micrograms per milliliter (µg/mL)
timeFrame: At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)
measure: Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Africa/Stage 2, and between-group ratios
timeFrame: At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)
measure: Anti-serotype specific immunoglobulin G (IgG) within-participant geometric mean ratios (GMRs) in participants in Africa/Stage 2
timeFrame: At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)
measure: Number of participants in Africa/Stage 2 achieving, for each antigen (Ag), at least a 4-fold rise in anti-serotype specific immunoglobulin G (IgG) antibody concentration
timeFrame: At Days 29, 85 and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
measure: Number of participants in Africa/Stage 2 with Anti-S. Typhi Vi antigen (Ag) immunoglobulin G (IgG) antibody concentrations equivalent to ≥ 4.3 micrograms per milliliter (µg/mL)
timeFrame: At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Blantyre 3
country: Malawi
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: