Safety and Immunogenicity of a 10 Valent Pneumococcal Conjugate Vaccine (SIILPCV10) in Healthy Adults, Toddlers, Infants

Pneumococcal Disease Clinical Trial

Official title: A Phase 1/2, Prospective,Randomized, Active-Controlled, Double-Blind, Age De-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's PCV10 in Healthy Adults, Toddlers, and Infants

Status Completed

Clinical Trial Summary

Phase 1/2, Prospective, Single Center, Randomized, ActiveControlled, Double-Blind, Age De-escalation Study to assess the safety and tolerability of SIILPCV10 administered as a single-dose regimen to healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve young adults and PCV-primed toddlers through 4 weeks post vaccination.

Each adult and toddler subject will undergo a total of 4 clinic visits. Each infant subject will undergo a total of 9 scheduled visits. Blood will be collected from all subjects during the screening visit for safety and potential immunological assessments, and 28 days after completion of the vaccination schedule for immunological assessments. For adults, the vaccine was given intramuscularly into the mid-deltoid muscle of nondominant arm using a 24-gauge needle. For toddlers and infants, the vaccine will be given IM into the anterolateral aspect of the left thigh. Blood will be collected from adults and toddlers for safety labs at the Day 7 post-vaccination visit.

Clinical Trial Description

This was a prospective, single-center, randomized, active-controlled, double-blind, age de escalation study in healthy Gambian PCV-naïve adults (18-40 years old), PCV primed toddlers (12-15 months old) and PCV-naïve infants (6-8 weeks old).

In the adult cohort, at least 34 eligible PCV-naïve adults (18-40 years old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Pneumovax 23 in a 1:1 ratio on Day 0 (V1), with stratification by sex (although no fixed proportion of males and females was required in the cohort as a whole).

In the toddler cohort, at least 112 eligible PCV-primed toddlers (12-15 months old) were planned to be randomized into the study to receive a single dose of either SIILPCV10 or Prevenar 13 in a 1:1 ratio on Day 0 (V1).

Each adult and toddler subject underwent a total of 4 clinic visits, including at least 1 screening visit (V0) no more than 14 days prior to Day 0, a vaccination visit on Day 0 (V1), and follow-up clinic visits at 7 (+3) and 28 (+14) days after vaccination (V2 and V3, respectively). A total of 3 blood samples were obtained for laboratory safety and immunogenicity assessments.

In the infant cohort, at least 200 eligible PCV-naïve infants (6 to 8 weeks old) were randomized into the study to receive 3 doses of either SIILPCV10 or Prevenar 13 in a 1:1 ratio along with standard Expanded Program on Immunisation (EPI) vaccinations (pentavalent diphtheria, tetanus, whole-cell pertussis, hepatitis B, and Haemophilus influenzae type b combined vaccine [DTwP-HepB-Hib], oral poliovirus vaccine [OPV], rotavirus vaccine [RV], and inactivated poliovirus vaccine [IPV]).

Each infant subject underwent a total of 9 scheduled visits for the primary series: at least 1 screening visit (V0); 3 primary vaccination visits at 28 (+14)-day intervals (V1, 3, 5); follow-up clinic visits at 7 (+3) days after each primary vaccination (V2, 4, 6); and 2 follow-up visits 28 and 84 days after the last primary vaccination (V7 and V8, respectively). Windows for follow-up and subsequent vaccination visits were calculated based on the actual calendar date of the prior vaccination, rather than relative to the day of randomization. Vaccinations included the blinded PCV study vaccine (SIILPCV10 or Prevenar 13) and the unblinded EPI vaccines (DTwP-HepB-Hib, OPV, RV, and IPV).

A total of 2 blood samples were obtained for the primary series (V0 and V7), with the first sample used for safety laboratory eligibility assessment, and if randomized, for baseline immunogenicity testing. Immunogenicity testing was also done on the second sample.

During the supplemental booster phase, infant subjects underwent 2 additional visits: a fourth (booster) vaccination visit (V9) at ≥ 9 months of age, and a follow-up visit 28 days after the booster dose (V10). The EPI vaccines scheduled for 9 months of age in The Gambia were not given as part of the study. However, study personnel contacted parents of infant subjects to remind them of the need to attend this EPI vaccination visit at the due date to allow for effective scheduling of the subsequent booster. The vaccine (SIILPCV10 or Prevenar 13) was given at least 4 weeks after the routine EPI vaccines given at 9 months of age in The Gambia (measles and rubella, yellow fever, and OPV). Infants who received SIILPCV10 at V9 were offered a booster dose of Prevenar 13 at least 56 days following the SIILPCV10 boost. Immunogenicity testing was performed on 2 additional blood samples collected during the booster phase (V9 and V10).

In the adult and toddler cohorts, on the day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia and a urine pregnancy test was performed (in adult women who were not surgically sterile) to rule out pregnancy before final eligibility was confirmed and randomization occurred. In the infant cohort, on each day of vaccination, a malaria rapid test was performed using a finger prick to rule out parasitemia before vaccination occurred. Any infant showing signs of acute illness or abnormal vital signs on the day of vaccination were not vaccinated until recovery was documented by the study team.

After all vaccinations, subjects were monitored for solicited reactogenicity. All adult and toddler subjects were monitored for AEs at each clinic visit until V3, and ongoing AEs at study exit were followed until last subject last visit (LSLV). Infant subjects were monitored for AEs at each clinic visit until V8. For infants who participated in the booster phase of the study, AEs were recorded at V10, and any conditions present at V9 were considered baseline.

SAS software was used to analyze data. ;

Related Conditions & MeSH terms

• Pneumococcal Disease
• Pneumococcal Infections

• NCT number: NCT02308540
• Study type: Interventional
• Source: PATH
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 12, 2015
• Completion date: November 3, 2016