Kang David W, Connor Robert J, Nekoroski Tara, Bitsura Jo Ann M, Kindig Susan K, Knowles Stephen P, LaBarre Michael J
Halozyme Therapeutics, Inc. (Innovation Department), San Diego, CA, USA.
Halozyme Therapeutics, Inc, 12390 El Camino Real, San Diego, CA, 92130, USA.
Drug Deliv Transl Res. 2025 May 30. doi: 10.1007/s13346-025-01883-z.
Until recently, approved handheld auto-injectors (AIs) have been limited to volumes ≤ 2 mL. A prototype rapid high-volume AI (HVAI) that can deliver 10 mL in 30 s was developed to administer therapeutics co-formulated with a proprietary recombinant human hyaluronidase PH20 (rHuPH20). This phase I, open-label study assessed the tolerability of subcutaneous (SC) injections of 10% (100 mg/mL) immunoglobulin G (IgG) solution co-administered with 4000 U/mL rHuPH20, delivered using a syringe pump at a target rate of 5 or 10 mL/30 seconds or the prototype HVAI at a target rate of 10 mL/30 seconds in healthy human subjects. Subjects received 5 mL (Cohort A, n = 12) or 10 mL (Cohort B, n = 12) of test solution via syringe pump (injection visit 1), and 10 mL of test solution via HVAI (Cohorts A & B; injection visit 2). Primary endpoints were tolerability and safety outcomes. Secondary endpoints included HVAI injection duration. All 24 subjects completed visit 1; 23/24 completed visit 2. All injections were tolerated, with no serious adverse events (AEs). Following syringe pump administration, 6/24 subjects (25%) reported eight treatment-emergent AEs (TEAEs); after HVAI administration, 4/23 (17%) reported four TEAEs, all mild in severity. Mean (± SEM) injection duration via HVAI was 27.9 ± 0.8 s. Most subjects (91%, 21/23) experienced no or mild injection-site pain following HVAI administration, and 96% (22/23) said they would be willing to have the HVAI injection again. SC injection of a 10% IgG solution in combination with rHuPH20 was well tolerated at an injection rate of 10 mL/~30 s using the prototype HVAI.
直到最近，已获批的手持式自动注射器（AI）的容量都限制在≤2 mL。研发了一种原型快速大容量自动注射器（HVAI），它能够在30秒内注射10 mL，用于注射与一种专利重组人透明质酸酶PH20（rHuPH20）共同配制的治疗药物。这项I期开放标签研究评估了在健康人类受试者中，皮下（SC）注射与4000 U/mL rHuPH20共同给药的10%（100 mg/mL）免疫球蛋白G（IgG）溶液的耐受性，使用注射器泵以5或10 mL/30秒的目标速率给药，或使用原型HVAI以10 mL/30秒的目标速率给药。受试者通过注射器泵接受5 mL（A组，n = 12）或10 mL（B组，n = 12）测试溶液（注射访视1），并通过HVAI接受10 mL测试溶液（A组和B组；注射访视2）。主要终点是耐受性和安全性结果。次要终点包括HVAI注射持续时间。所有24名受试者完成了访视1；23/24完成了访视2。所有注射均耐受，无严重不良事件（AE）。在通过注射器泵给药后，6/（24名受试者（25%）报告了8例治疗中出现的不良事件（TEAE）；在通过HVAI给药后，4/23（17%）报告了4例TEAE，均为轻度。通过HVAI的平均（±SEM）注射持续时间为27.9±0.8秒。大多数受试者（91%，21/23）在通过HVAI给药后未出现或仅出现轻度注射部位疼痛，96%（22/23）表示他们愿意再次接受HVAI注射。使用原型HVAI以10 mL/约30秒的注射速率皮下注射10% IgG溶液与rHuPH20的组合耐受性良好。
