Clinical trial NCT03896477: Study of 10-valent Pneumococcal Conjugate Vaccine (Pneumosil) Administered in a 2+1 Schedule to Healthy Infants
Official title: A Phase 3, Randomized, Observer-Blind Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's 10-Valent Pneumococcal Conjugate Vaccine (PNEUMOSIL®) Administered in a 2+1 Schedule to Healthy Infants in The Gambia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Pneumococcal
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Serum Institute of India Pvt. Ltd.
name: Medical Research Council Unit, The Gambia
name: University College, London
name: FHI 360
First posted: 2019-04-01
Enrollment: 660
Sex: ALL
Minimum age (years): 42
Maximum age (years): 56
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objectives of this study are to evaluate the immunogenicity (antibody response) and safety and tolerability of a 2-dose primary series and booster dose (2+1 schedule) of Pneumosil co-administered with routine pediatric vaccines in healthy infants in The Gambia.

Detailed description: This study will provide data necessary to evaluate the safety and immunogenicity of Pneumosil when administered in an alternative schedule to the 3 dose primary schedule (3+0) evaluated in the Phase 3 pivotal trial (VAC-056; NCT03197376) - namely in a 2 dose primary and booster (2+1) schedule - and compare immunogenicity to that of both currently licensed second-generation pneumococcal conjugate vaccines (Synflorix and Prevenar 13) administered in the same 2+1 schedule.

In this prospective, single center, randomized, active-controlled, observer-blind, Phase 3 descriptive study, 660 healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve infants will be randomized 1:1:1 to receive 3 doses of either Pneumosil, Synflorix or Prevenar 13 at 6 weeks, 14 weeks and 9-10 months of age. Standard Expanded Program on Immunization (EPI) vaccinations in The Gambia will be given concomitantly with all 3 doses of study vaccine.

The booster vaccination window was extended up to 18 months of age due to a pause in the study due to the coronavirus disease 2019 (COVID-19) pandemic. The study schedule for participants is as follows:

* Age 6 weeks: First primary vaccination dose administered
* Age 14 weeks: Second primary vaccination dose administered (8 weeks after first primary dose)
* Age 18 weeks: Blood sample for immunogenicity testing (4 weeks after second primary dose)
* Age 9-18 months: Blood sample for immunogenicity testing and booster vaccination dose administered
* Age 10-19 months: Blood sample for immunogenicity testing (4 weeks after booster dose)

Eligibility criteria: Inclusion Criteria:

* Healthy infants based on medical history and clinical assessment.
* Between 6 and 8 weeks (ie 42 to 56 days) old, inclusive.
* Subject's parent must provide voluntary written/thumb-printed informed consent and be willing to comply with study requirements and procedures.
* Subjects must have been born full-term, have a weight-to-height Z score of ≥ -2 at the time of enrollment (WHO child growth standard), and be ≥ 3.5 kg at randomization.
* Subject's parents must be available for the duration of trial participation

Exclusion Criteria:

* Use of any investigational medicinal product prior to randomization.
* Previous vaccination against or infection with S. pneumoniae.
* History of anaphylactic shock or an allergic reaction to any prior vaccination.
* Any fever, illness (including malaria).
* Receipt of another study vaccine within 30 days of study start.
* Chronic administration of an immunosuppressant or administration of immunoglobulins
* History of blood disorder, primary immunodeficiency, or a sibling who has such a diagnosis or who died suddenly without apparent cause.
* History of meningitis, seizures or any neurological disorder.
* Exposure to human immunodeficiency virus (HIV) by history.

Primary outcomes:
measure: Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster
timeFrame: 4 weeks post booster dose
measure: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination
timeFrame: Day 0 to Day 6 after each vaccination
measure: Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs)
timeFrame: AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall.
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall.
Secondary outcomes:
measure: Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster
timeFrame: 4 weeks post booster dose
measure: Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster
timeFrame: 4 weeks post booster dose
measure: Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster
timeFrame: 4 weeks post booster dose
measure: Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster
timeFrame: 4 weeks post booster dose
measure: Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
measure: Geometric Mean Concentration of Serotype-specific IgG Antibodies Four Weeks After Completion of Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
measure: Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks After Completion of Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
measure: Geometric Mean Titers of Serotype-specific Serum OPA Four Weeks After Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
measure: Percentage of Participants With Serotype-specific Serum IgG Concentrations ≥ 0.35 μg/mL Prior to Booster
timeFrame: Prior to the booster dose at approximately 9 to 16 months of age
measure: Geometric Mean Concentration of Serotype-specific Serum IgG Antibodies Prior to Booster
timeFrame: Prior to the booster dose at approximately 9 to 16 months of age
measure: Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Prior to Booster
timeFrame: Prior to the booster dose at approximately 9 to 16 months of age
measure: Geometric Mean Titer of Serotype-specific Serum OPA Prior to Booster
timeFrame: Prior to the booster dose at approximately 9 to 16 months of age
measure: Ratio of Serotype-specific Serum IgG GMC 4 Weeks Post-Booster to Serotype-specific IgG GMC 4 Weeks After Completion of Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster
measure: Ratio of Serotype-specific Serum OPA GMT 4 Weeks Post-Booster to Serotype-specific OPA GMT 4 Weeks After Completion of Primary Vaccinations
timeFrame: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster
Other outcomes:
Locations:
city: Banjul
country: Gambia
facility: Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM)
Study officials:
affiliation: MRCG at LSHTM
name: Ed Clarke, MB ChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: