Table 10.
Comparison of prototype digital enzyme-linked immunosorbent assay (Simoa) amyloid-β 1–42 peptide assay with the Quanterix commercial Simoa assay in the context of use as a pharmacodynamic marker in β-site amyloid precursor protein cleaving enzyme 1 inhibitor clinical trials
| ELISA | LLOQ (pg/ml; ±20%) | Mean baseline (pg/ml) (SD) | Maximum percentage reduction (SD) | Maximum quantifiable percentage reduction (±20%) |
|---|---|---|---|---|
| Quanterix commercial Aβ1–42 assay performance | ||||
| Aβ1–42 peptide calibrator | ||||
| Quanterix | 0.274 (0.220–0.329)a | 17.1 (2.16)b | 64 (5)c | 98 (96.5–98.7) |
| Fujirebio | 0.824 (0.659–0.989)a | 39.6 (4.93)b | 64 (5)c | 98 (95.4–98.3) |
| Prototype Simoa Aβ1–42 assay performance | ||||
| Aβ1–42 peptide calibrator | ||||
| Quanterix | 1.2 (0.96–1.44) | 18.7 (2.04)d | 75 (3)e | 94 (92.3–94.9) |
| Fujirebio | 2.8 (2.24–3.36) | 44.35 (4.99)d | 79 (3)e | 94 (92.4–94.9) |
Aβ amyloid-β, ELISA Enzyme-linked immunosorbent assay, LLOQ Lower limit of quantification
Note: Quanterix assay data show the maximum reduction of signal observed in I4O-MC-BACA and the assay’s maximum quantifiable percentage reduction limit for the Quanterix commercial assay. Prototype Simoa assay data show results for the same parameters when using the newly developed Simoa assay
aLLOQ based on lowest standard with replicate performance <20% coefficient of variation
bBaseline values are calculated from study I4O-MC-BACA (not shown)
cMaximum percentage reduction calculated from 35-mg dose group of study I4O-MC-BACA (not shown)
dMean baseline values are calculated from study I4O-MC-BACA (Table 3)
eMaximum percentage reduction calculated from 35-mg dose group of study I4O-MC-BACA (Table 5)