A Study on the Safety, Reactogenicity, and Immune Response to the GVGH iNTS-GMMA Vaccine Against Invasive Nontyphoidal Salmonella in Adults, Children, and Infants

GlaxoSmithKline (GSK)

Status and phase

Enrolling

Phase 2

Conditions

Salmonella Infections

Treatments

Biological: Pentavalent vaccine

Biological: iNTS-GMMA Dose C

Drug: Placebo

Biological: Measles and Rubella vaccine

Biological: iNTS-GMMA Dose A

Biological: MenACWY

Biological: Pneumococcal vaccine

Biological: Inactivated polio vaccine

Biological: iNTS-GMMA Dose B

Combination Product: DTPa-HBV-IPV+Hib

Biological: Yellow Fever vaccine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06213506

217218

Details and patient eligibility

About

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 on children (24-59 months of age) and finally to infants (9 months and 6 weeks of age). Infants are the target for primary vaccination from 6 weeks of age.

Full description

The study will be conducted in two stages:

Stage 1: Age De-escalation from Adults to Children and Infants

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 85 (Priming phase), and Day 232 (Booster phase).

Stage 2: Dose-finding in Infants of 6 weeks of age

-Infants (6 weeks of age) will receive one of the three dose levels (Dose A [low], Dose B [medium], or Dose C [high]) of the candidate vaccine or the control on Day 1, Day 85 (Priming phase), and Day 232 (Booster phase).

Enrollment

516 estimated patients

Sex

All

Ages

6 weeks to 50 years old

Volunteers

Accepts Healthy Volunteers

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 at 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 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 WHO Z-score less than -2 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/exclusion criteria have been re-checked, and if the participant is confirmed to be eligible.

Administration of long-acting immune-modifying drugs at any time during the study period.
Administration of immunoglobulins and/or any blood products or plasma derivatives from birth (for infant 6 weeks of age) or during the period starting 3 months before the administration of the first dose of study intervention(s) 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) up to the end of the study. For corticosteroids, this will mean prednisone equivalent greater than or equal to (>=) 20 mg/day for adult participants/ >= 0.5 mg/kg/day with maximum of 20 mg/day for pediatric participants (infants and children). 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, drug and device).

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.
Child in care.

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Quadruple Blind

516 participants in 22 patient groups

Adults_Dose C Group

Experimental group

Description:

Adults 18-50 years of age, part of the safety cohort, randomized to receive 2 doses of the iNTS-GMMA Dose C vaccine at Day 1 and Day 57.

Treatment:

Biological: iNTS-GMMA Dose C

Adults_Control Group

Active Comparator group

Description:

Adults 18-50 years of age, part of the safety cohort, randomized to receive 1 dose of the MenACWY vaccine at Day 1 and 1 dose of Placebo at Day 57.

Treatment:

Drug: Placebo

Biological: MenACWY

Children_Dose B Group

Experimental group

Description:

Children 24-59 months of age, part of the safety cohort, randomized to receive 2 doses of the iNTS-GMMA Dose B vaccine at Day 1 and Day 57.

Treatment:

Biological: iNTS-GMMA Dose B

Children_Control B Group

Active Comparator group

Description:

Children 24-59 months of age, part of the safety cohort, randomized to receive 2 doses of the MenACWY vaccine at Day 1 and Day 57.

Treatment:

Biological: MenACWY

Children_Dose C Group

Experimental group

Description:

Children 24-59 months of age, part of the safety cohort, randomized to receive 2 doses of the iNTS-GMMA Dose C vaccine at Day 1 and Day 57.

Treatment:

Biological: iNTS-GMMA Dose C

Children_Control C Group

Active Comparator group

Description:

Children 24-59 months of age, part of the safety cohort, randomized to receive 2 doses of the MenACWY vaccine at Day 1 and Day 57.

Treatment:

Biological: MenACWY

Infants_9M_Dose A Group

Experimental group

Description:

Infants 9 months of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose A vaccine at Day 1, Day 85 and Day 169. These infants also receive an Expanded Program on Immunization (EPI) vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the first study intervention administration occurring at Day 1, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose A

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_9M_Control A Group

Active Comparator group

Description:

Infants 9 months of age, part of the safety cohort, randomized to receive 2 doses of the MenACWY vaccine at Day 1 and Day 85 and 1 dose of the DTPaHBV-IPV+Hib vaccine at Day 169. These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the first study intervention administration occurring at Day 1, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Combination Product: DTPa-HBV-IPV+Hib

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_9M_Dose B Group

Experimental group

Description:

Infants 9 months of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose B vaccine at Day 1, Day 85 and Day 169. These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the first study intervention administration occurring at Day 1, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose B

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_9M_Control B Group

Active Comparator group

Description:

Treatment:

Combination Product: DTPa-HBV-IPV+Hib

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_9M_Dose C Group

Experimental group

Description:

Infants 9 months of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose C vaccine at Day 1, Day 85 and Day 169. These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the first study intervention administration occurring at Day 1, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose C

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_9M_Control C Group

Active Comparator group

Description:

Treatment:

Combination Product: DTPa-HBV-IPV+Hib

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Dose A Group

Experimental group

Description:

Infants 6 weeks of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose A vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the third study intervention administration occurring at Day 232, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose A

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Control A Group

Active Comparator group

Description:

Infants 6 weeks of age, part of the safety cohort, randomized to receive 3 doses of the MenACWY vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). To allow completion of the vaccination schedule a fourth dose of the MenACWY vaccine is administered after the trial ends, as per the licensed indication and in private vaccination settings. These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the third study intervention administration occurring at Day 232, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Dose B Group

Experimental group

Description:

Infants 6 weeks of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose B vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the third study intervention administration occurring at Day 232, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose B

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Control B Group

Active Comparator group

Description:

Treatment:

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Dose C Group

Experimental group

Description:

Infants 6 weeks of age, part of the safety cohort, randomized to receive 3 doses of the iNTS-GMMA Dose C vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine at 28 days after the third study intervention administration occurring at Day 232, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose C

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Control C Group

Active Comparator group

Description:

Treatment:

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Infants_6W_Dose A_2 Group

Experimental group

Description:

Infants 6 weeks of age, part of the dose-finding cohort, randomized to receive 3 doses of the iNTS-GMMA Dose A vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with the following vaccines: Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine administered concomitantly during the last iNTS-GMMA administration at Day 232, and the pentavalent vaccine (DTPwHepB-Hib), the Pneumococcal conjugate vaccine, and the inactivated polio vaccine administered at the same time, at 6, 10 and 14 weeks of age, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: Inactivated polio vaccine

Biological: Pneumococcal vaccine

Biological: iNTS-GMMA Dose A

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Biological: Pentavalent vaccine

Infants_6W_Dose B_2 Group

Experimental group

Description:

Infants 6 weeks of age, part of the dose-finding cohort, randomized to receive 3 doses of the iNTS-GMMA Dose B vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with the following vaccines: Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine administered concomitantly during the last iNTS-GMMA administration at Day 232, and the pentavalent vaccine (DTPwHepB-Hib), the Pneumococcal conjugate vaccine, and the inactivated polio vaccine administered at the same time, at 6, 10 and 14 weeks of age, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: Inactivated polio vaccine

Biological: iNTS-GMMA Dose B

Biological: Pneumococcal vaccine

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Biological: Pentavalent vaccine

Infants_6W_Dose C_2 Group

Experimental group

Description:

Infants 6 weeks of age, part of the dose-finding cohort, randomized to receive 3 doses of the iNTS-GMMA Dose C vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). These infants also receive an EPI vaccination with the following vaccines: Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine administered concomitantly during the last iNTS-GMMA administration at Day 232, and the pentavalent vaccine (DTPwHepB-Hib), the Pneumococcal conjugate vaccine, and the inactivated polio vaccine administered at the same time, at 6, 10 and 14 weeks of age, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: iNTS-GMMA Dose C

Biological: Inactivated polio vaccine

Biological: Pneumococcal vaccine

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Biological: Pentavalent vaccine

Infants_6W_Control_2 Group

Active Comparator group

Description:

Infants 6 weeks of age, part of the dose-finding cohort, randomized to receive 3 doses of the MenACWY vaccine at Day 1, Day 57 (during the Priming phase) and at Day 232 (during the Booster phase). To allow completion of the vaccination schedule a fourth dose of the MenACWY vaccine is administered after the trial ends, as per the licensed indication and in private vaccination settings. These infants also receive an EPI vaccination with the following vaccines: Measles and Rubella Vaccine (MR-VAC) and Yellow Fever (YF) vaccine administered concomitantly during the last study intervention administration at Day 232, and the pentavalent vaccine (DTPw-HepB-Hib), the Pneumococcal conjugate vaccine, and the inactivated polio vaccine administered at the same time, at 6, 10 and 14 weeks of age, at the local EPI vaccination centers, and not part of the current clinical trial.

Treatment:

Biological: Inactivated polio vaccine

Biological: Pneumococcal vaccine

Biological: MenACWY

Biological: Measles and Rubella vaccine

Biological: Yellow Fever vaccine

Biological: Pentavalent vaccine