Efficacy and safety of rademikibart (CBP-201), a next-generation mAb targeting IL-4Rα, in adults with moderate to severe atopic dermatitis : A phase 2 randomized trial (CBP-201-WW001)
Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody.
OBJECTIVE: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis.
METHODS: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021.
RESULTS: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct.
CONCLUSIONS: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:153 |
|---|---|
| Enthalten in: |
The Journal of allergy and clinical immunology - 153(2024), 4 vom: 15. Apr., Seite 1040-1049.e12 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Silverberg, Jonathan I [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jaci.2023.11.924 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366485857 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366485857 | ||
| 003 | DE-627 | ||
| 005 | 20240416232423.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240108s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jaci.2023.11.924 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1377.xml |
| 035 | |a (DE-627)NLM366485857 | ||
| 035 | |a (NLM)38157942 | ||
| 035 | |a (PII)S0091-6749(23)02546-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Silverberg, Jonathan I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy and safety of rademikibart (CBP-201), a next-generation mAb targeting IL-4Rα, in adults with moderate to severe atopic dermatitis |b A phase 2 randomized trial (CBP-201-WW001) |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.04.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody | ||
| 520 | |a OBJECTIVE: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis | ||
| 520 | |a METHODS: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021 | ||
| 520 | |a RESULTS: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct | ||
| 520 | |a CONCLUSIONS: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atopic dermatitis | |
| 650 | 4 | |a CBP-201 | |
| 650 | 4 | |a dosing frequency | |
| 650 | 4 | |a efficacy | |
| 650 | 4 | |a rademikibart | |
| 650 | 4 | |a safety | |
| 650 | 4 | |a tolerability | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Strober, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Feinstein, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jinhua |e verfasserin |4 aut | |
| 700 | 1 | |a Guttman-Yassky, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Simpson, Eric L |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Longphre, Malinda |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Jiawang |e verfasserin |4 aut | |
| 700 | 1 | |a Yun, Jang |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Belinda |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Wubin |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Selwyn |e verfasserin |4 aut | |
| 700 | 1 | |a Collazo, Raúl |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Zheng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of allergy and clinical immunology |d 1971 |g 153(2024), 4 vom: 15. Apr., Seite 1040-1049.e12 |w (DE-627)NLM000018449 |x 1097-6825 |7 nnns |
| 773 | 1 | 8 | |g volume:153 |g year:2024 |g number:4 |g day:15 |g month:04 |g pages:1040-1049.e12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jaci.2023.11.924 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 153 |j 2024 |e 4 |b 15 |c 04 |h 1040-1049.e12 | ||