A Phase 1/2, Randomized, Placebo-Controlled, Observer-Blind Study to Assess the Safety, Tolerability, and Immunogenicity of Streptococcus pneumoniae Whole Cell Vaccine, Inactivated and Adsorbed to Aluminum Hydroxide (PATH-wSP) in Healthy Kenyan Young Adults (18 to 40 years) and Toddlers (12 to 21 months)

This study (VAC-040) is required to assess the safety and tolerability of the single-vial formulation of PATH-wSP manufactured by Bio Farma, prior to use of this new formulation in such an infant population in a Phase 2 dose-ranging, proof-of-concept study. This randomized, placebo-controlled, observer-blind trial is designed to sequentially evaluate PATH‑wSP at two escalating doses (0.6 mg and 1 mg) in both adults and toddlers.  The following cohorts will be tested:

Adult (18-40 years old) Cohorts:

• Two 0.6 mg doses of PATH-wSP (12 subjects) or saline (12 subjects) with a 28-day interval between doses.
• Two 1 mg doses of PATH-wSP (12 subjects) or saline (12 subjects) with a 28-day interval between doses.

Toddler (12-21 months old) Cohorts:

• Two 0.6 mg doses of PATH-wSP (50 subjects) or saline (50 subjects) with a 56-day interval between doses, and pentavalent vaccine co-administered with the second dose.
• Two 1 mg doses of PATH-wSP (50 subjects) or saline (50 subjects) with a 56-day interval between doses, and pentavalent vaccine co-administered with the second dose.

Each adult subject will undergo a total of 6 scheduled visits, including at least one screening visit no more than 28 days prior to vaccination (Visit 0), two vaccination visits (scheduled 28 days apart), two safety visits at 7 days post each vaccination and a final visit at 28 days post the final vaccination.

Each toddler subject will undergo a total of 8 scheduled visits, including at least one screening visit no more than 28 days prior to vaccination (Visit 0), two vaccination visits (scheduled 56 days apart), and five safety visits at 7 and 28 days after the first vaccination and at 7, 28, and 56 days after the second dose.

Daily reactogenicity assessments for 7 days post vaccination will be completed in all subjects by fieldworkers using a standard home visit diary.

For all subjects, blood draws for safety laboratory tests and/or PATH-wSP-induced immune responses will be performed at screening (baseline safety and immunogenicity), 7 days after each study vaccination (safety only) and 28 days after the second vaccination (immunogenicity only).

Primary objectives of this study are:

• To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1 mg) of PATH-wSP vaccine, administered in a 2-series schedule, 4 weeks apart, in healthy adults.
• To evaluate the safety and tolerability of 2 dose levels (0.6 mg and 1 mg) of PATH-wSP vaccine, administered in a 2-series schedule, 8 weeks apart, in healthy toddlers when co-administered with a booster dose of licensed pentavalent vaccine (diphtheria, tetanus, whole-cell pertussis, Haemophilus influenzae type b, and hepatitis B combined vaccine) at the second vaccination.