Opportunistic Pneumococcal Immunisation Trial in MALnutrition (OPTIMAL)

Immunogenicity of Opportunistic Pneumococcal Conjugate Vaccination (Pneumosil®) Versus Control (Typhoid Conjugate Vaccine, Typbar TCV®) in Children Aged 6-59 Months Hospitalised With Severe Acute Malnutrition: a Single-centre, Double-blind, Randomised Controlled Trial in Timor-Leste

The goal of the OPTIMAL clinical trial is to learn if a dose of a pneumococcal conjugate vaccine (PCV) generates a good immune response in young children who are in hospital with severe acute malnutrition.

Researchers will compare an intervention group who get a dose of a PCV (Pneumosil) to a control group who get a dose of a Typhoid conjugate vaccine (Typbar TCV). To ensure all participants receive timely potential benefits, at 3 months participants in the intervention group with receive a dose of Typbar TCV, and those in the conrol group will receive a dose of Pneumosil.

Participants will be visited 4 times at their homes over six months after vaccination, with a phone review at 12 months after vaccination.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumococcal Disease; Pneumococcal Vaccines; Pneumococcal Infection; Pneumonia in Children; Severe Acute Malnutrition in Childhood
• Intervention / Treatment: Biological: Pneumococcal conjugate vaccine; Biological: Typhoid conjugate vaccine

Detailed Description

This is a prospective, single-centre, double-blind, randomised controlled trial in 264 children aged 6-59 months hospitalised with severe acute malnutrition.

Participants will be randomised (1:1) to receive either a dose of a pneumococcal conjugate vaccine (Pneumosil, the intervention group) or a dose of a Typhoid conjugate vaccine (Typbar TCV, the control group). Stratification for randomisation will be done on (a) prior immunisation with a PCV (confirmed or unknown/unvaccinated); and (b) severity of malnurition (weight-for-height/length z-score <-4 or >=-4). Participants will be enrolled as soon as practical after admission to hospital, while randomisation and vaccine administration will occur once the participant is medically stable in the 'transition phase' of SAM care.

The primary objective is to demonstrate that immune responses to the 10 pneumococcal serotypes in Pneumosil are better in participants who receive Pneumosil, compared to those who receive Typbar TCV, when measured 28 days after vaccination.

• Study Type: Interventional
• Enrollment (Estimated): 214
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nicholas S. S. Fancourt, PhD; Phone Number: +61889468600; Email: nick.fancourt@menzies.edu.au
• Study Contact Backup: Name: Jane N Nelson, Bachelor of Nursing; Phone Number: +61889468600; Email: jane.nelson@menzies.edu.au

Study Locations

• Timor-Leste
  • Timor-Leste
    • Dili, Timor-Leste, Timor-Leste
      • Guido Valadares National Hospital (HNGV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 6-59 months at the time of hospitalisation

2. Hospitalised with severe acute malnutrition (SAM, defined as any one of a, b, or c):

   1. weight-for-length/height z-score <-3; or
   2. middle upper arm circumference <11.5cm; or
   3. bilateral pitting pedal oedema unexplained by other causes
3. Parent/carer is willing for their child to participate in the study and has provided written informed consent
4. Parent/carer is willing to comply with all study procedures outlined in the protocol, including specimen collection, for the duration of the study

Exclusion Criteria:

1. Known history of allergy or hypersensitivity to any component of either study vaccine, including diphtheria toxoid, or a history of anaphylactic shock.
2. Treatment with another investigational drug or other intervention in the 30 days prior to randomisation, or ongoing participation in another clinical trial.
3. Suspected primary or secondary immunodeficiency or prolonged administration (>14 days) of an immune modifying drug (including oral glucocorticoids) in the past 3 months.
4. Known terminal illness expected to result in death within 6 months.
5. Participants who, in the opinion of the site Principal Investigator, are unable to comply with the study protocol, including scheduled visits, assessments, and any other protocol-required procedures.
6. Previously enrolled in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm: Pneumosil	Biological: Pneumococcal conjugate vaccine; 10-valent pneumococcal polysaccharide conjugate vaccine at a dosage of 2μg for each serotype polysaccharide for 1, 5, 6A, 7F, 9V, 14, 19A, 19F, 23F, and 4μg for serotype 6B, conjugated to a carrier protein (CRM197), polysorbate 20 and aluminium phosphate as an adjuvant. Administered as an intramuscular injection of 0.5mL.
Other: Control Arm: Typbar TCV	Biological: Typhoid conjugate vaccine; Typhoid conjugate vaccine at a dosage of 25μg purified Vi capsular polysaccharide of Salmonella typhi Ty2 conjugated to Tetanus Toxoid with preservative (2-Phenoxyethanol). Administered as an intramuscular injection of 0.5mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype-specific immunoglobulin G (IgG) antibodies	Pneumosil serotype-specific (1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 23F) immunoglobulin G (IgG) geometric mean concentrations (GMCs).	4 weeks after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype-specific IgG antibodies	Pneumosil serotype-specific IgG GMCs	4 weeks and 3 months after vaccination
Proportion of participants with serotype-specific IgG antibody responses ≥ 0.35 μg/mL	Proportion of participants with Pneumosil serotype-specific IgG concentrations ≥ 0.35μg/mL	4 weeks and 3 months after vaccination
Functional antibody responses	Pneumosil serotype-specific pneumococcal geometric mean opsonisation indices (GMOIs)	4 weeks and 3 months after vaccination
Functional antibody responses	Proportion of participants with Pneumosil serotye-specfiic pneumococcal opsonisation indices (OIs) >8	4 weeks and 3 months after vaccination
Salivary IgG antibodies	Serotype-specific salivary IgG (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C	4 weeks and 3 months after vaccination
Salivary immunoglobulin A (IgA) antibodies	Serotype-specific salivary IgA (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C	4 weeks and 3 months after vaccination
Nasopharyngeal carriage of pneumococcus	Proportion of participants with nasopharyngeal carriage of Pneumosil vaccine-type pneumococci and their antimicrobial resistance patterns	3 months after vaccination
Severe acute malnutrition recovery	Weight-for-height/length z-score >= -2 or MUAC >12.5cm	Reviewed at all study visits until completion (12 months after vaccination)
Re-hospitalisation	Any repeat admission to hospital as confirmed by medical records	3 months and 12 months after vaccination
Mortality	Deaths as reported. Cause of death determined from review of medial records.	3 and 12 months after vaccination
Composite illness or mortality	Repeat hospitalisation(s) or death.	Reviewed at all study visits until completion (12 months after vaccination)
Salmonella Typhi antibodies	Proportion of paticipants with >4 fold rise (compared to pre-vaccination) of Salmonella Typhi anti-Vi IgG geometric mean titres (GMTs)	4 weeks and 3 months after vaccination for all participants, plus 4 months and 6 months after vaccination for participants in the control arm

Collaborators and Investigators

• Sponsor: Nick Fancourt
• Collaborators: University of Edinburgh; Murdoch Childrens Research Institute; The University of Western Australia; Timor-Leste Ministry of Health

Publications and helpful links

Helpful Links

• Pneumosil product information
• Typbar-TCV product information

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pneumonia; Pneumococcal infection; Pneumococcal vaccine; Pneumococcal disease; Pneumococcal; Severe Acute Malnutrition in childhood; Pneumosil
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Pneumonia; Pneumococcal Infections; Biological Products; Complex Mixtures; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Pneumococcal Vaccines
• Other Study ID Numbers: MENTL2024-4996; U1111-1312-6848 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Plan for IPD sharing is in development.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No