Long-term Persistence of Immunogenicity After Primary Vaccination and Response to Booster Vaccination With Typhoid Conjugate Vaccine: Results of a Phase IV Extension Study.

OBJECTIVE: To evaluate the persistence of antibodies three years after primary vaccination with typhoid conjugate vaccine (TCV) of either Cadila Healthcare Ltd. (Cadila-TCV) or Bharat Biotech International Ltd. (Bharat-TCV) administered in a previous phase II/III study, and to study the booster dose response to Cadila-TCV. METHODS: This was an open-label, phase IV extension study conducted in tertiary care and multispecialty hospitals in India. 112 subjects (Cadila-TCV-57, Bharat-TCV-55) who had participated in previous study were enrolled. Of these, eligible subjects received a single-dose of Cadila-TCV and were followed-up for 28 days post-booster. Primary outcome was persistence of antibodies 3 years after primary vaccination and seroconversion (≥4-fold rise in antibody titre from baseline) 28 days post-booster. Safety was based on reported adverse events (AEs) post-booster. RESULTS: The baseline GMT reported in the current study was significantly higher than pre-vaccination GMT reported in the previous study. 89/112 (79.5%) subjects had antibody titer ≥10 IU/mL at baseline; eligible subjects (n=17) who had baseline antibody titre <10 IU/mL were administered booster dose. All the vaccinated subjects showed seroconversion post-booster. The GMTs reported at 10 days and 28 days post-booster were significantly higher as compared to GMTs reported after primary vaccination in previous study. 4 (23.5%) vaccinated subjects reported 9 AEs; all were solicited and of mild/moderate intensity. CONCLUSIONS: There was a significant persistence of immunogenicity after primary vaccination with both the TCVs, and robust immune response after booster vaccination with Cadila-TCV.

Immunogenicity and Safety of Typhoid Conjugate Vaccine in Healthy Indian Subjects: A Randomized, Active-controlled, Comparative Clinical Trial.

OBJECTIVE: To compare the immunogenicity and safety of an investigational typhoid Vi conjugate vaccine (Test TCV) with a marketed typhoid Vi conjugate vaccine (Comparator TCV). DESIGN: Randomized, controlled trial. SETTING: Tertiary care and multispecialty hospitals. PARTICIPANTS: 240 healthy subjects of 6 months to 45 years. Pediatric (<18 years) subjects were enrolled after day 21 safety assessment of adult subjects. INTERVENTION: Participants received a single-dose of test TCV or comparator TCV at baseline and were followed up for 6 weeks post-vaccination. MAIN OUTCOME MEASURE: Primary variable was to demonstrate non-inferiority of the test TCV with the comparator TCV for seroconversion post-vaccination (³4-fold rise in antibody titre). Secondary variables were seroconversion in the adult and pediatric cohorts, and geometric mean titre of antibodies while the safety was based on reported adverse events. RESULTS: A total of 117 subjects (Adult-58, Pediatric-59) and 119 subjects (Adult-60, Pediatric-59) in test and comparator group, respectively completed the study. The seroconversion rate with test TCV (overall-94.8%, adult-96.6% and pediatric-93.1%) was non-inferior to comparator TCV (overall-91.6%, adult-91.7% and pediatric-91.5%). The geometric mean titres of antibodies (EU/mL) at baseline (test TCV: overall-7.6, adult-10.0, and pediatric-5.7; and comparator TCV: overall-8.0, adult-12.0, and pediatric-5.3) and at end of study (test TCV: overall-1121.0, adult-1411.0 and pediatric-891.1; and comparator TCV: overall-1104.0, adult-1199.0 and pediatric-1014.0) were also comparable between the groups (P>0.05 for all). The most common adverse event was injection-site pain followed by fever in both the groups. CONCLUSIONS: The immunogenicity and safety of test TCV is comparable to already marketed comparator TCV.

Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate in comparison with chloroquine phosphate in children with acute uncomplicated Plasmodium vivax malaria: A phase III, randomised, multicentric study.

BACKGROUND & OBJECTIVES: In India, the burden of Plasmodium vivax malaria has been projected to be highest in some areas. This study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate (AM) 37.5 mg and piperaquine phosphate 187.5 mg (PQP) dispersible tablets and (not with) chloroquine in the treatment of uncomplicated vivax malaria in pediatric patients. METHODS: This multicentric, open-label trial was carried out at 12 sites in India. A total of 164 patients aged 6 months to 12 years with P. vivax malaria were randomized in a ratio of 2:1 to AM-PQP (111 patients) or chloroquine (53 patients) arms. The duration of follow up was 42 days. RESULTS: At 72 hours, the proportion of a parasitaemic and afebrile patients was 100% in both treatment arms in per protocol (PP) population, and 98.2% and 100% [95% CI: -1.8 (-6.33 to 5.08)] in AM-PQP and chloroquine arms, respectively, in intent to treat (ITT) population. The efficacy and safety of AM-PQP was found to be comparable to chloroquine in the treatment of uncomplicated P. vivax malaria in pediatric patients. Overall, the cure rate at Day 28 and 42 was >95% for both AM-PQP or CQ. The commonly reported clinical adverse event was vomiting. No patient was discontinued for any QTc abnormality. INTERPRETATION & CONCLUSION: The efficacy and safety of FDC of arterolane maleate and piperaquine phosphate was found to be comparable to chloroquine for treatment of uncomplicated P. vivax malaria in pediatric patients.