Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China

Abstract

IntroductionThe invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7).Methods and analysis1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12–15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed.Ethics and disseminationEthics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance.Trial registration numberNCT02736240.

Immunogenicity and seroefficacy of pneumococcal conjugate vaccines – a systematic review and network meta-analysis

“…10,11,18-89 18 studies (20 publication records) were excluded from the analysis: 6 studies did not provide individual patient or aggregate data, [70][71][72][73] and 12 studies (14 publication records) were head-to-head studies with the vaccines of interest, but it was not possible to form a loop within the network meta-analysis to provide indirect evidence (See Supplementary Figure 1 and Supplementary Table 2). [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89] Of these 12 studies, 8 reported results from different PCVs including a new Cuban PCV7, PCV10-SII, PCV11, PCV12, a Chinese PCV13, PCV14, PCV15, PCV20, PCV24 and PCV SP0202-VI. The remaining 27 studies (53 publication records) from 2009 to 2022 were included in the network meta-analyses.…”

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data

“…1 ), of which 47 studies (78 publication reports) satisfied our eligibility criteria. 10 , 11 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ,…”

“…S1 and Supplementary Table S2 ). 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 93 , 94 , 95 , 96 The remaining 28 studies (54 publication records) from 2009 to 2023 were included in the network meta-analyses. 10 , 11 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ,…”

Comparison of three sample size calculation methods for non-inferiority vaccine trials with multiple continuous co-primary endpoints

“…The lower limit of the confidence interval for the difference between μ T and μ C should be greater than -d, which is the same as requiring the lower limit of the confidence interval for the ratio of the geometric means e μ T and e μ C greater than λ, where d = ln(1/λ). A commonly used margin [19][20][21][22] for the ratio is ln(1/2), which means that the experimental vaccine be at least half as efficacious as the control vaccine.…”