Ji Su Lee, WonSerk Kim, Chong-Hyun Won, Yang-Won Lee, SeungHwan Lee, Heejae Won, Soon-Jae Park, Sunbae Lee, Seol-Hee Kim, Jiwon Yang, Gahee Bahn, Dong Hun Lee
{"title":"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：一项随机、双盲、安慰剂对照的健康志愿者一期研究","authors":"Ji Su Lee, WonSerk Kim, Chong-Hyun Won, Yang-Won Lee, SeungHwan Lee, Heejae Won, Soon-Jae Park, Sunbae Lee, Seol-Hee Kim, Jiwon Yang, Gahee Bahn, Dong Hun Lee","doi":"10.1007/s13555-025-01507-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05232175.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Safety, Tolerability, and Pharmacokinetics of ALT-BB4 (A Novel Recombinant Hyaluronidase): A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study in Healthy Volunteers.\",\"authors\":\"Ji Su Lee, WonSerk Kim, Chong-Hyun Won, Yang-Won Lee, SeungHwan Lee, Heejae Won, Soon-Jae Park, Sunbae Lee, Seol-Hee Kim, Jiwon Yang, Gahee Bahn, Dong Hun Lee\",\"doi\":\"10.1007/s13555-025-01507-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05232175.</p>\",\"PeriodicalId\":11186,\"journal\":{\"name\":\"Dermatology and Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Dermatology and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13555-025-01507-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dermatology and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13555-025-01507-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
The Safety, Tolerability, and Pharmacokinetics of ALT-BB4 (A Novel Recombinant Hyaluronidase): A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study in Healthy Volunteers.
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.
期刊介绍：
Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
