Opportunistic Pneumococcal Immunisation Trial in MALnutrition

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Serotype-specific immunoglobulin G (IgG) antibodies [Time frame: 4 weeks after vaccination]

Secondary outcome measures (12)

• Serotype-specific IgG antibodies [Time frame: 4 weeks and 3 months after vaccination]
• Proportion of participants with serotype-specific IgG antibody responses ≥ 0.35 μg/mL [Time frame: 4 weeks and 3 months after vaccination]
• Functional antibody responses [Time frame: 4 weeks and 3 months after vaccination]
• Functional antibody responses [Time frame: 4 weeks and 3 months after vaccination]
• Salivary IgG antibodies [Time frame: 4 weeks and 3 months after vaccination]
• Salivary immunoglobulin A (IgA) antibodies [Time frame: 4 weeks and 3 months after vaccination]
• Nasopharyngeal carriage of pneumococcus [Time frame: 3 months after vaccination]
• Severe acute malnutrition recovery [Time frame: Reviewed at all study visits until completion (12 months after vaccination)]
• Re-hospitalisation [Time frame: 3 months and 12 months after vaccination]
• Mortality [Time frame: 3 and 12 months after vaccination]
• Composite illness or mortality [Time frame: Reviewed at all study visits until completion (12 months after vaccination)]
• Salmonella Typhi antibodies [Time frame: 4 weeks and 3 months after vaccination for all participants, plus 4 months and 6 months after vaccination for participants in the control arm]

Eligibility criteria

Inclusion criteria

• Aged 6-59 months at the time of hospitalisation
• Hospitalised with severe acute malnutrition (SAM, defined as any one of a, b, or c):

• weight-for-length/height z-score <-3; or
• middle upper arm circumference <11.5cm; or
• bilateral pitting pedal oedema unexplained by other causes
• Parent/carer is willing for their child to participate in the study and has provided written informed consent
• 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

• Known history of allergy or hypersensitivity to any component of either study vaccine, including diphtheria toxoid, or a history of anaphylactic shock.
• Treatment with another investigational drug or other intervention in the 30 days prior to randomisation, or ongoing participation in another clinical trial.
• Suspected primary or secondary immunodeficiency or prolonged administration (>14 days) of an immune modifying drug (including oral glucocorticoids) in the past 3 months.
• Known terminal illness expected to result in death within 6 months.
• 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.
• Previously enrolled in this trial.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Timor-Leste · 1 center

• Guido Valadares National Hospital (HNGV) — Dili

Identifiers

NCT: NCT06817421 · MENTL2024-4996 · U1111-1312-6848

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗