Endpoints and assessments
EVENTS, SECONDARY, BLOOD
The primary endpoint of this trial was the assessment of the safety and tolerability of multiple subcutaneous injections of SHR-1222. The secondary endpoints included PKs, PDs, and the immunogenicity of SHR-1222.Adverse events (AEs), coded according to the preferred terms of the Medical Dictionary for Regulatory Activities v25.0, were monitored and recorded. Clinical laboratory evaluations, vital signs, and 12-lead electrocardiograms were conducted for safety assessments.Blood samples for PKs and PDs were collected in the morning after an overnight fast for at least 10 hours at 19 time points: days 1, 3, 7, 15, 22, 29, 57, 85, 113, 141 (at predose if dosing); the day after the last dose of the study treatment for 2, 4, 6, 14, or 21 d (days 115, 117, 119, 127, 134 for Q2M cohorts; days 143, 145, 147, 155, and 162 for QM cohorts); and days 169, 197, and 225. PK analyses were performed at Shanghai InnoStar Bio-tech Co., Ltd., including area under the curve from time 0 to the last measurable concentration (AUCAll subjects underwent lumbar spine (L1–L4) and hip (total hip and femoral neck) DXA scans for BMD measurements during the screening period, and on days 57, 85, 169, 197, and 225, using the same Hologic Discovery Wi Bone Densitometer (Hologic, Bedford, MA, United States) at each center. Instrument quality controls were produced to ensure the coefficient of variation (CV) under 1.5% throughout the study to ensure the accuracy of the results.Blood samples for anti-SHR-1222 antibody determination were collected on days 1, 7, 29, 57, 85, 113, 141 (at pre-dose if dosing), 6 d after the last dose of study treatment (days 119 and 147 for Q2M and QM cohorts, respectively), and on day 225. Anti-SHR-1222 antibody was detected at Shanghai InnoStar Bio-tech Co., Ltd. using a validated Meso Scale Discovery electrochemiluminescence immunoassay. Blood samples were stored or transported at ultra-low temperatures ranging from -100°C to -60°C and analyzed in batches.