Clinical trial NCT06817421: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Severe Acute Malnutrition in Childhood
Pneumococcal Disease
Pneumococcal Vaccines
Pneumococcal Infection
Pneumonia in Children
Keywords: Pneumococcal
Severe Acute Malnutrition in childhood
Pneumococcal vaccine
Pneumosil
Pneumococcal disease
Pneumococcal infection
Pneumonia
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: Murdoch Childrens Research Institute
name: The University of Western Australia
name: University of Edinburgh
name: Timor-Leste Ministry of Health
First posted: 2025-02-10
Enrollment: 264
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, single-centre, double-blind, phase 4, randomised, controlled trial in children aged 6-59 months hospitalised with severe acute malnutrition.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serotype-specific immunoglobulin G (IgG) antibodies
timeFrame: 6 months after vaccination
Secondary outcomes:
measure: Serotype-specific IgG antibodies
timeFrame: 4 weeks and 12 months after vaccination
measure: Proportion of participants with serotype-specific IgG antibody responses ≥ 0.35 μg/mL
timeFrame: 4 weeks, 6 months, and 12 months after vaccination
measure: Functional antibody responses
timeFrame: 4 weeks and 6 months after vaccination
measure: Salivary IgG antibodies
timeFrame: 4 weeks and 6 months after vaccination
measure: Salivary immunoglobulin A (IgA) antibodies
timeFrame: 4 weeks and 6 months after vaccination
measure: Nasopharyngeal carriage of pneumococcus
timeFrame: 4 weeks, 6 months, and 12 months after vaccination
measure: Lower respiratory tract infection
timeFrame: Reviewed at all study visits until completion (12 months after vaccination)
measure: Hospitalisation
timeFrame: Reviewed at all study visits until completion (12 months after vaccination)
measure: Severe acute malnutrition recovery
timeFrame: Reviewed at all study visits until completion (12 months after vaccination)
measure: Mortality
timeFrame: Reviewed at all study visits until completion (12 months after vaccination)
measure: Composite illness or mortality
timeFrame: Reviewed at all study visits until completion (12 months after vaccination)
Other outcomes:
Locations:
city: Dili
country: Timor-Leste
facility: Guido Valadares National Hospital (HNGV)
Study officials:
References: