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

  • Dermatol Ther (Heidelb). 2025 Nov;15(11):3301-3311. doi: 10.1007/s13555-025-01507-x.
Ji Su Lee  1  2 ,  WonSerk Kim  3 ,  Chong-Hyun Won  4 ,  Yang-Won Lee  5 ,  SeungHwan Lee  6 ,  Heejae Won  6  7 ,  Soon-Jae Park  8 ,  Sunbae Lee  8 ,  Seol-Hee Kim  8 ,  Jiwon Yang  8 ,  Gahee Bahn  8 ,  Dong Hun Lee  9  10  11
Affiliations
  • 1. Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 2. Department of Dermatology, Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center, Seoul, Republic of Korea.
  • 3. Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • 4. Department of Dermatology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
  • 5. Department of Dermatology, Konkuk University School of Medicine, Seoul, Republic of Korea.
  • 6. Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Korea.
  • 7. Department of Biomedical Sciences, Seoul National University Hospital, Seoul, Korea.
  • 8. Alteogen Inc., Daejeon, Korea.
  • 9. Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea. [email protected].
  • 10. Department of Dermatology, Seoul National University Hospital, Seoul National University Collge of Medicine, Seoul, Republic of Korea. [email protected].
  • 11. Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea. [email protected].
PMID: 40892310 DOI: 10.1007/s13555-025-01507-x
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.

Keywords
Clinical trial; Drug delivery; Hyaluronic acid; Hyaluronidase.
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