NCT02097472

Dose-Finding Study of S.Pneumoniae Whole Cell Vaccine Adsorbed to Alum (PATH-wSP) in Healthy Kenyan Adults and Toddlers

A Dose-Finding Study to Assess the Safety, Tolerability, and Immunogenicity of Inactivated Streptococcus Pneumoniae Whole Cell Vaccine Formulated With Alum (PATH-wSP) in Healthy Kenyan Young Adults and PCV-Primed Toddlers

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 304 (actual)
• Sponsor: PATH · Academic / Other
• Sex: All
• Age: 12 Months – 45 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to assess the safety and tolerability of PATH-wSP, administered intramuscularly to healthy Kenyan adults and toddlers who have been primed with a pneumococcal conjugate vaccine (PCV). Additionally, the study will explore whether a measurable immune response is elicited when PATH-wSP is administered to healthy Kenyan adults and toddlers who have been primed with PCV.

Detailed description

S. pneumoniae whole cell vaccine (SPWCV) is a vaccine candidate made from whole, unencapsulated pneumococcal cells. S. pneumoniae whole cell antigen bulk was manufactured at Walter Reed Army Institute of Research from strain RM200 RX1E PdT ΔlytA and is inactivated with beta-propiolactone. Pneumolysin, a proven virulence factor, was genetically knocked out in SPWCV and replaced with pneumolysoid, a derivative carrying the toxin gene with 3 point mutations known to abolish both cytolytic activity and complement activation. When adsorbed to aluminum hydroxide (alum), SPWCV is utilized as the vaccine candidate Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant (PATH-wSP) for clinical investigation. PATH-wSP has been previously tested in adults in a Phase 1 trial in the US, in which doses of 100 to 600 μg were given to healthy young adults in a 3-vaccination series and showed a favorable safety, tolerability, and immunogenicity profile. This study was a dose escalation and age de-escalation study, and sequential cohorts of subjects were identified to allow safety evaluations of dosing and ages to occur progressively during the study. The following PATH-wSP cohorts were defined for adult and toddler subjects: * Adult Cohort 1: 600 μg PATH-wSP or saline * Adult Cohort 2: 1000 μg PATH-wSP or saline * Toddler Cohort 1: 300 μg PATH-wSP and/or active control vaccines * Toddler Cohort 2: 600 μg PATH-wSP and/or active control vaccines.

Conditions

• Pneumonia, Pneumococcal

Interventions

Type	Name	Description
BIOLOGICAL	PATH-wSP	Streptococcus pneumoniae Whole Cell Vaccine adsorbed to Alum
BIOLOGICAL	Synflorix	1 dose (0.5 mL) contains: 1 μg of each of the following pneumococcal polysaccharide serotypes: 1, 5, 6B, 7F, 9V, 14, and 23 F And 3 μg of the following pneumococcal polysaccharide serotypes: 4, 18C and 19F. The serotypes are conjugated to either: protein D (derived from Non-Typeable Haemophilus influenzae) carrier protein, tetanus toxoid carrier protein or diphtheria toxoid carrier protein
BIOLOGICAL	Pentavac	Each PFS contains 0.5 ml (single dose): Diphtheria Toxoid 20 Lf to 30 Lf Tetanus Toxoid 2.5 Lf to 10 Lf B. Pertussis 4 IU HBsAg (rDNA) 10 mcg Purified capsular HIB Polysaccharide (PRP) Conjugated to Tetanus Toxoid (carrier protein) 10 mcg Adsorbed on Aluminium Phosphate, AL+++ 1.25 mg Preservative: Thiomersal 0.005 % Dose: O.5ml by intramuscular injection.
OTHER	Saline	0.9% Sodium Chloride Injection, USP

Timeline

• Start date: 2014-04-01
• Primary completion: 2015-12-01
• Completion: 2015-12-01
• First posted: 2014-03-27
• Last updated: 2019-10-10
• Results posted: 2018-06-12

Locations

1 site across 1 country: Kenya