Meso scale discovery platform

Safety endpoints were the incidence of adverse events (AEs) in the treatment period and follow-up period; abnormalities in laboratory test parameters, electrocardiograms (ECG), vital signs, and weight; and immunogenicity. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA, version 20.1). Samples for laboratory testing, vital signs, and weight were collected at screening, baseline, week 4, week 12, week 24, and week 52/discontinuation. ECG was performed at screening, week 24, and week 52/discontinuation. For the evaluation of immunogenicity, anti-teriparatide antibodies and neutralizing activities were analyzed in serum samples collected at baseline and week 52/discontinuation. Anti-teriparatide antibodies were detected with a validated electrochemiluminescent immunoassay using the Meso Scale Discovery platform (Meso Scale Diagnostics, LLC., Rockville, MD, USA) and biotinylated RGB-10 and SULFO-TAG-labeled RGB-10. A validated cell-based assay (CatchPoint cyclic-AMP fluorescent assay kit; Molecular Devices Japan K.K., Tokyo, Japan) was used to measure neutralizing activities. Assessments for neutralizing activities were conducted only in samples positive for anti-teriparatide antibodies. Samples for laboratory testing and immunogenicity analysis were centrally analyzed at the same facility as for P1NP (LSI Medience Corp., Tokyo, Japan).

Plasma, serum, and peripheral blood mononuclear cells samples were collected at predetermined timepoints for endpoint analysis [27 ]. Human immunodeficiency virus testing was conducted using an algorithm, and HIV immunoassays were also evaluated for cross-reactivity.
Plasma samples for PK analysis were collected before and 1, 3, and 7 days and 2, 4, 8, 12, 16, and 24 weeks after the first dose. Participants who received a second bnAb dose had additional PK samples up to 24 weeks after the second dose. For VRC07-523LS, a quantitative electrochemiluminescence sandwich immunoassay technique was performed on the Meso Scale Discovery platform. For PGT121, an enzyme-linked immunoassay platform was used [29 (link), 31 ]. To determine neutralizing activity, a TZM-bl-neutralizing antibody assay using env-pseudotyped viruses was used [32 (link)] (Supplementary Text).