Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy : Results from the First-in-Human study
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy.
METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab.
RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab.
CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111706 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ye, Young-Min [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111706 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Ye, Young-Min |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy |b Results from the First-in-Human study |
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| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy | ||
| 520 | |a METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab | ||
| 520 | |a RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab | ||
| 520 | |a CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a (6 max): Atopy | |
| 650 | 4 | |a Allergy | |
| 650 | 4 | |a IgE | |
| 650 | 4 | |a Mast cell | |
| 650 | 4 | |a anti-IgE antibody | |
| 650 | 7 | |a Omalizumab |2 NLM | |
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| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Immunoglobulin E |2 NLM | |
| 650 | 7 | |a 37341-29-0 |2 NLM | |
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| 650 | 7 | |a 147205-72-9 |2 NLM | |
| 700 | 1 | |a Park, Jung-Won |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sae-Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, You Sook |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sook Young |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sae Young |e verfasserin |4 aut | |
| 700 | 1 | |a Sim, Sujin |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Eunji |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Bomin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jieon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Su Kyung |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Myoung Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Hae-Sim |e verfasserin |4 aut | |
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