Dose-Finding Study of S.Pneumoniae Whole Cell Vaccine Adsorbed to Alum (PATH-wSP) in Healthy Kenyan Adults and Toddlers
Condition: Pneumonia, Pneumococcal
MeSH terms: Pneumonia; Pneumonia, Pneumococcal
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): PATH-wSP; Synflorix; Pentavac; Saline
Intervention type(s): Biological; Biological; Biological; Other
Intervention description(s): Streptococcus pneumoniae Whole Cell Vaccine adsorbed to Alum; 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; 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.; 0.9% Sodium Chloride Injection, USP
Other intervention name(s): 10-valent Pneumococcal Conjugate Vaccine (PCV10); Diptheria Pertussis Tetanus Hep B Haemophilus b Conjugate
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention