Table 3.
Outcomes of immunogenicity readouts according to hypothesis 1–3.
| Method | Readouts | Estimated median difference with 95% CI | p- values | ||
|---|---|---|---|---|---|
| PRIMARY PRIORITY |
Hypothesis 1 Day 0–84 etoricoxib vs controls |
FLUOROSPOT (FS) | Cytokine+ to SUM Ag85B+ESAT6+CFP10 | −19.3 (−136 to 97.7) | 0.74 |
| IFNγ to SUM Ag85B+ESAT6+CFP10 | −28.3 (−128.9 to 72.2) | 0.57 | |||
| Whole blood ICS (WB-ICS) |
Cytokine+ to PPD Cytokine+ to SUM Ag85B+ESAT6+Rv2660c |
−0.47 (−1.02 to 0.071) −0.18 (−0.46 to 0.10) |
0.09 0.21 |
||
|
Hypothesis 2 Day 84–154 H56:IC31 vs controls |
FLUOROSPOT (FS) | Cytokine+ to H56 | 149.7 (22.0 to 277.3) | 0.02 | |
| IFNγ to H56 | 93.8 (25.2 to 162.4) | 0.01 | |||
| Cytokine+ to SUM Ag85B+ESAT6 | 214.3 (11.77 to 416.9) | 0.04 | |||
| Whole blood ICS (WB-ICS) | Cytokine+ to SUM Ag85B+ESAT6+Rv2660c | 0.33 (−0.78 to 1.44) | 0.54 | ||
| ELISA serology | IgG antibody to H56 | 1.15 (−3.89 to 6.1) | 0.64 | ||
|
Hypothesis 3 Day 84–154 etoricoxib+H56:IC31 vs H56:IC31 |
FLUOROSPOT (FS) | Cytokine+ to H56 | −176.3 (−352.0 to −0.6) | 0.05 | |
| IFNγ to H56 | −109.2 (−215.7 to −2.7) | 0.05 | |||
| Cytokine+ to SUM Ag85B+ESAT6 | −252.7 (−495.6 to −9.7) | 0.04 | |||
| Whole blood ICS (WB-ICS) | Cytokine+ to SUM Ag85B+ESAT6+Rv2660c | −0.37 (−1.57 to 0.84) | 0.53 | ||
| ELISA serology | IgG antibody to H56 | −0.86 (−20.8 to 19.1) | 0.93 | ||
| SECONDARY PRIORITY |
Hypothesis 2 Day 84–154 H56:IC31 vs controls |
Whole blood ICS (WB-ICS) | IFNγ+ IL2+ TNFα+ CD4 to Ag85B | 0.04 (0.00 to 0.090) | 0.05 |
| IFNγ+ IL2+ TNFα+ CD4 to ESAT6 | 0.01 (−0.08 to 0.10) | 0.79 | |||
| IFNγ+ IL2+ TNFα+ CD4 to Rv2660c | 0.00 (−0.01 to 0.01) | 0.79 | |||
| IFNγ+ IL2+ TNFα+ CD4 to SUM Ag85B+ESAT6+Rv2660c | 0.09 (−0.04 to 0.21) | 0.16 | |||
| IFNγ- IL2+ TNFα+ CD4 to Ag85 | 0.01 (−0.01 to 0.04) | 0.30 | |||
| IFNγ- IL2+ TNFα+ CD4 to ESAT6 | 0.02 (−0.02 to 0.05) | 0.32 | |||
| IFNγ- IL2+ TNFα+ CD4 to Rv2660c | 0.00 (−0.00 to 0.00) | 1.00 | |||
| IFNγ- IL2+ TNFα+ CD4 to SUM Ag85B+ESAT6+Rv2660c | 0.03 (−0.02 to 0.08) | 0.29 | |||
| IFNγ+ IL2+ TNFα− CD4 to Ag85B | 0.02 (0.00 to 0.03) | 0.03 | |||
| IFNγ+ IL2+ TNFα− CD4 to ESAT6 | 0.01 (−0.00 to 0.02) | 0.12 | |||
| IFNγ+ IL2+ TNFα− CD4 to Rv2660c | 0.00 (−0.00 to 0.01) | 0.58 | |||
| IFNγ+ IL2+ TNFα− CD4 to SUM Ag85B+ESAT6+Rv2660c | 0.05 (−0.00 to 0.09) | 0.05 | |||
| IFNγ+ IL2- TNFα+ CD4 to Ag85 | 0.05 (0.01 to 0.08) | 0.01 | |||
| IFNγ+ IL2- TNFα+ CD4 to ESAT6 | 0.02 (−0.00 to 0.04) | 0.08 | |||
| IFNγ+ IL2- TNFα+ CD4 to Rv2660c | 0.01 (−0.00 to 0.03) | 0.13 | |||
| IFNγ+ IL2- TNFα+ CD4 to SUM Ag85B+ESAT6+Rv2660c | 0.10 (0.02 to 0.17) | 0.02 |
Table 3 Outcomes of immunogenicity analyses readouts for hypothesis 1–3 according to pre-assigned hierarchical order in the statistical plan to compensate for lack of multiple testing and facilitate interpretation. For Hypothesis 1 etoricoxib consists of both the etoricoxib group and the etoricoxib+H56:IC31 group (before vaccination) and controls consists of both the control group and the H56:IC31 group (before vaccination). Upper part of table shows primary priority outcomes. Lower part shows posthoc analysis of readouts defined as secondary priority outcomes. The treatment differences were calculated as estimated difference in median response with 95% confidence intervals based on 1000 bootstrap replications and corresponding two-sided p-value. The significant p-values are in bold.