ALT-BB4（一种新型重组透明质酸酶）的安全性、耐受性和药代动力学：一项在健康志愿者中进行的随机、双盲、安慰剂对照的1期研究。

The Safety, Tolerability, and Pharmacokinetics of ALT-BB4 (A Novel Recombinant Hyaluronidase): A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study in Healthy Volunteers.

作者信息

Lee Ji Su, Kim WonSerk, Won Chong-Hyun, Lee Yang-Won, Lee SeungHwan, Won Heejae, Park Soon-Jae, Lee Sunbae, Kim Seol-Hee, Yang Jiwon, Bahn Gahee, Lee Dong Hun

机构信息

Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Department of Dermatology, Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center, Seoul, Republic of Korea.

出版信息

Dermatol Ther (Heidelb). 2025 Sep 2. doi: 10.1007/s13555-025-01507-x.

DOI:10.1007/s13555-025-01507-x

PMID:40892310

Abstract

INTRODUCTION

Hyaluronidase has been used as an adjuvant to facilitate subcutaneous drug delivery by degrading hyaluronic acid, a viscoelastic barrier in subcutaneous tissue. However, traditional animal-derived hyaluronidases raise safety concerns, including risk of anaphylaxis and zoonoses. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of ALT-BB4, a novel recombinant hyaluronidase derived from human hyaluronidase PH20, in healthy adults.

METHODS

This first-in-human, multicenter, randomized, double-blinded, placebo-controlled phase 1 study included 244 participants who received single intradermal or subcutaneous injections of ALT-BB4 or placebo. The study was conducted in three parts: part I assessed drug allergy reactions, part II-A evaluated pharmacokinetics, and part II-B assessed safety and tolerability.

RESULTS

Intradermal injection of ALT-BB4 exhibited a low incidence of drug allergy reactions (0.4%), with no significant difference compared with placebo (p = 0.317). Subcutaneous injection of ALT-BB4 resulted in more frequent injection site treatment emergent adverse events (TEAEs) compared with placebo (16.9% versus 0%; p < 0.001). All injection site TEAEs were mild, self-resolving, and did not require treatment. Systemic TEAEs were less frequent in the ALT-BB4 group compared with placebo (0.7% versus 5.6%; p = 0.045), and no serious adverse events were reported. Notably, no antidrug antibodies were detected. Pharmacokinetic analysis revealed minimal systemic absorption of ALT-BB4.

CONCLUSIONS

Both intradermal and subcutaneous injection of ALT-BB4 demonstrated excellent safety and tolerability, supporting its potential as a promising alternative to traditional animal-derived hyaluronidases. Future studies are warranted to confirm these findings in broader clinical settings.

TRIAL REGISTRATION

ClinicalTrials.gov identifier, NCT05232175.

摘要

引言

透明质酸酶已被用作佐剂，通过降解皮下组织中的粘弹性屏障透明质酸来促进皮下药物递送。然而，传统的动物源性透明质酸酶引发了安全问题，包括过敏反应和人畜共患病风险。本研究旨在评估一种源自人透明质酸酶PH20的新型重组透明质酸酶ALT-BB4在健康成年人中的安全性、耐受性和药代动力学。

方法

这项首次人体、多中心、随机、双盲、安慰剂对照的1期研究纳入了244名参与者，他们接受了单次皮内或皮下注射ALT-BB4或安慰剂。该研究分为三个部分：第一部分评估药物过敏反应，第二部分A评估药代动力学，第二部分B评估安全性和耐受性。

结果

皮内注射ALT-BB4的药物过敏反应发生率较低（0.4%），与安慰剂相比无显著差异（p = 0.317）。与安慰剂相比，皮下注射ALT-BB4导致注射部位治疗出现的不良事件（TEAE）更频繁（16.9%对0%；p < 0.001）。所有注射部位TEAE均为轻度，可自行缓解，无需治疗。与安慰剂相比，ALT-BB4组的全身性TEAE较少（0.7%对5.6%；p = 0.045），且未报告严重不良事件。值得注意的是，未检测到抗药抗体。药代动力学分析显示ALT-BB4的全身吸收极少。