A Study to Evaluate the Safety, Reactogenicity, and Immune Response of the GSK Vaccines Institute for Global Health (GVGH) Quadrivalent Pan-Salmonella Vaccine With and Without Alum in Healthy Young Adults

Official title

A Phase 1, Randomized, Controlled, Observer-blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of the GVGH Quadrivalent Pan-Salmonella Vaccine With and Without Alum in Healthy Adults 18 to 45 Years of Age in Africa

Overview

The current clinical study will evaluate the GVGH Quadrivalent Pan-Salmonella vaccine for the first time in healthy adults in Africa. The purpose of the current Phase 1 study is to evaluate the safety, reactogenicity, and the immune response induced by the Pan-Salmonella vaccine.

Interventions

• Biological Pan-Salmonella-with-Alum (Low dose) vaccine
  Participants receive low dose of the Pan-Salmonella-with-Alum.
• Biological Pan-Salmonella-with-Alum (Full dose) vaccine
  Participants receive full dose of the Pan-Salmonella-with-Alum.
• Biological Pan-Salmonella-without-Alum (Low dose) vaccine
  Participants receive low dose of the Pan-Salmonella-without-Alum.
• Biological Pan-Salmonella-without-Alum (Full dose) vaccine
  Participants receive full dose of the Pan-Salmonella-without-Alum.
• Biological Typhoid Vi conjugate vaccine
  Participants receive Typhoid Vi conjugate vaccine as control
• Other Placebo
  Participants receive Placebo (saline solution) as control.

Primary outcome measures

• Number of participants with solicited administration site events [Time frame: From Day 1 to Day 7]
• Number of participants with solicited administration site events [Time frame: From Day 61 to Day 67]
• Number of participants with solicited administration site events [Time frame: From Day 181 to Day 187]
• Number of participants with solicited systemic events [Time frame: From Day 1 to Day 7]
• Number of participants with solicited systemic events [Time frame: From Day 61 to Day 67]
• Number of participants with solicited systemic events [Time frame: From Day 181 to Day 187]
• Number of participants with unsolicited events [Time frame: From Day 1 to Day 30]
• Number of participants with unsolicited events [Time frame: From Day 61 to Day 91]
• Number of participants with unsolicited events [Time frame: From Day 181 to Day 211]
• Number of participants with serious adverse events (SAEs) [Time frame: From Day 1 to Day 211]

Secondary outcome measures (11)

• Number of participants with serious adverse events (SAEs) [Time frame: From Day 211 to Day 361]
• Number of participants with AEs/SAEs leading to withdrawal from the study or discontinuation of study intervention [Time frame: From Day 211 to Day 361]
• Geometric mean concentration (GMC) of anti-serotype specific immunoglobulin G (IgG) antibody [Time frame: Pre-intervention at Day 1, Day 61 and Day 181]
• Adjusted GMC of anti-serotype specific IgG antibody [Time frame: Pre-intervention at Day 1, Day 61 and Day 181]
• GMC of anti-serotype specific IgG antibody [Time frame: At Day 31, Day 91 and Day 211]
• Adjusted GMC of anti-serotype specific IgG [Time frame: At Day 31, Day 91 and Day 211]
• Number of participants with anti-serotype specific IgG antibody concentration fold increase [Time frame: At Day 31, Day 91 and Day 211 compared with baseline (Day 1)]
• Number of participants with Anti-Vi Ag IgG antibody concentrations [Time frame: Pre-dose at Day 1, Day 61 and Day 181]
• Number of participants with Anti-Vi Ag IgG antibody concentrations [Time frame: At Day 31, Day 91 and Day 211]
• Number of participants with Anti-Vi Ag IgG antibody concentrations [Time frame: Pre-dose at Day 1, Day 61 and Day 181]
• Number of participants with Anti-Vi Ag IgG antibody concentrations [Time frame: At Day 31, Day 91 and Day 211]

Eligibility criteria

Inclusion criteria

• Participants 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 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\*.

\*Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, and human immunodeficiency virus (HIV) antibodies will also be tested at Screening.

• A male or female between and including 18 to 45 years of age at the time of the first study intervention administration, and no older than 45 years of age at second dose 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 menopause.
• Participants of childbearing potential may be enrolled in the study if the participant:

• Has practiced adequate contraception (as indicated in Section 10.5) for at least 30 days prior to study intervention administration, and
• Has a negative pregnancy test within 24 hours prior to the study intervention administration, and
• Has agreed to continue adequate contraception during the entire treatment period and for 8 weeks after completion of the study intervention administration series.
• Negative HLA-B27 testing.
• Body mass index of 18>= to <=30 kg/m2 at Screening.
• Living in the study area and plan to remain in the study area for the study duration.

Exclusion criteria

Medical Conditions:

• Known exposure to S. Typhi, S. Paratyphi A, and non-typhoidal Salmonella confirmed by blood culture during the period starting 3 years prior to first study intervention administration as confirmed using medical history.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• 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.
• Clinical conditions representing a contraindication to intramuscular (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.
• 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.

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, S. Paratyphi A, or GMMA vaccines in the participant's life.
• Use of any investigational or non-registered product (drug, vaccine, or medical device) 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.

Use of herbs and traditional treatments is not considered an exclusion criterion.

• A vaccine not foreseen by the study protocol administered during the period starting at 14 days before the first dose and ending 30 days after the last dose of study interventions administration, with the exception of flu vaccines or Coronavirus disease 2019 vaccine.
• Administration of long-acting immune-modifying drugs (e.g., infliximab) at any time during the study period.
• Administration of immunoglobulins 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 be prednisone equivalent >=20 mg/day for adult participants. Inhaled and topical steroids are allowed.

Prior/Concurrent Clinical Study Experience:

• Concurrently participating in another clinical study, 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.
• Any study personnel or their immediate dependents, family, or household members.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Triple blind

Primary purpose

Prevention

Study locations

South Africa · 1 center

• GSK Investigational Site — Bloemfontein

Identifiers

NCT: NCT07663032 · 300281

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗