Opportunistic Pneumococcal Immunisation Trial in MALnutrition

Phase 4

Not yet recruiting

• Conditions: Severe Acute Malnutrition in Childhood; Pneumonia in Children; Pneumococcal Disease; Pneumococcal Infection; Pneumococcal Vaccines
• Interventions: Biological: Pneumococcal conjugate vaccine; Biological: Typhoid conjugate vaccine

• Registration Number: NCT06817421
• Lead Sponsor: Nick Fancourt

Brief Summary

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).

Participants will be visited monthly at their homes for six months after vaccination, and then once more at 12 months after vaccination. At the end of their involvement in the study participants will be offered a dose of the vaccine they did not get while in hospital.

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 whoh receive Pneumosil, compared to those who receive Typbar TCV, when measured 6 months after vaccination.

Study Timeline

• Study First Submitted: 2025-01-28
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-04
• Last Update Submitted: 2025-02-07
• Study First Posted: 2025-02-10
• Last Update Posted: 2025-02-11
• Study Start: 2025-04
• Primary Completion: 2027-12
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

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

2. Hospitalised with severe acute malnutrition:

   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 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm: Pneumosil	Pneumococcal conjugate vaccine	-
Control Arm: Typbar TCV	Typhoid conjugate vaccine	-

Primary Outcome Measures

Name	Time	Method
Serotype-specific immunoglobulin G (IgG) antibodies	6 months after vaccination	Pneumosil serotype-specific (1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 23F) immunoglobulin G (IgG) geometric mean concentrations (GMCs).

Secondary Outcome Measures

Name	Time	Method
Salivary IgG antibodies	4 weeks and 6 months after vaccination	Serotype-specific salivary IgG (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C
Salivary immunoglobulin A (IgA) antibodies	4 weeks and 6 months after vaccination	Serotype-specific salivary IgA (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C
Composite illness or mortality	Reviewed at all study visits until completion (12 months after vaccination)	Lower respiratory tract infection(s), repeat hospitalisation(s), or death.
Mortality	Reviewed at all study visits until completion (12 months after vaccination)	Deaths as reported. Investigated with verbal autopsy and/or medical record review
Proportion of participants with serotype-specific IgG antibody responses ≥ 0.35 μg/mL	4 weeks, 6 months, and 12 months after vaccination	Proportion of participants with Pneumosil serotype-specific IgG concentrations ≥ 0.35μg/mL
Functional antibody responses	4 weeks and 6 months after vaccination	Pneumosil serotype-specific functional antibody responses measured by opsonophagocytic assays (OPAs)
Nasopharyngeal carriage of pneumococcus	4 weeks, 6 months, and 12 months after vaccination	Frequency and proportion of participants with nasopharyngeal carriage of Pneumosil vaccine-type pneumococci and their antimicrobial resistance patterns
Lower respiratory tract infection	Reviewed at all study visits until completion (12 months after vaccination)	Lower respiratory tract infection episodes determined by medical records and standardised parent questionnaire.
Hospitalisation	Reviewed at all study visits until completion (12 months after vaccination)	Admission to hospital as confirmed by medical records
Severe acute malnutrition recovery	Reviewed at all study visits until completion (12 months after vaccination)	Weight-for-height/length z-score \>= -2
Serotype-specific IgG antibodies	4 weeks and 12 months after vaccination	Pneumosil serotype-specific IgG GMCs

Trial Locations

Locations (1)

Guido Valadares National Hospital (HNGV); 🇹🇱 Dili, Timor-Leste