Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase Inhibitor, in Patients With Rheumatoid Arthritis : A Randomized, Double-blind, Placebo-controlled, 2-part Phase II Study
Copyright © 2021 by the Journal of Rheumatology..
OBJECTIVE: To evaluate the efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase in a 2-part, phase II trial (RAjuvenate; ClinicalTrials.gov: NCT02628028) in adults with active rheumatoid arthritis (RA).
METHODS: In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5, 10, or 30 mg or placebo once daily for 4 weeks to assess safety and tolerability. No safety signals precluded moving to Part B, where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5 mg (n = 63), 10 mg (n = 62), or 30 mg (n = 63), or placebo (n = 62) once daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary and secondary endpoints. Nonresponder imputation was used for missing data.
RESULTS: After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. One hundred and eighty-nine (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (P > 0.05 for all comparisons). Five serious adverse events occurred (n = 2, placebo; n = 3, 30 mg); there was 1 death due to a fall.
CONCLUSION: While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA.
| Errataetall: |
CommentIn: J Rheumatol. 2021 Jul;48(7):957-959. - PMID 33858981 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
The Journal of rheumatology - 48(2021), 7 vom: 15. Juli, Seite 969-976 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Genovese, Mark C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.10.2021 Date Revised 27.06.2022 published: Print-Electronic ClinicalTrials.gov: NCT02628028 CommentIn: J Rheumatol. 2021 Jul;48(7):957-959. - PMID 33858981 Citation Status MEDLINE |
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| doi: |
10.3899/jrheum.200893 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318886626 |
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| 245 | 1 | 0 | |a Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase Inhibitor, in Patients With Rheumatoid Arthritis |b A Randomized, Double-blind, Placebo-controlled, 2-part Phase II Study |
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| 500 | |a Date Completed 21.10.2021 | ||
| 500 | |a Date Revised 27.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02628028 | ||
| 500 | |a CommentIn: J Rheumatol. 2021 Jul;48(7):957-959. - PMID 33858981 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 by the Journal of Rheumatology. | ||
| 520 | |a OBJECTIVE: To evaluate the efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase in a 2-part, phase II trial (RAjuvenate; ClinicalTrials.gov: NCT02628028) in adults with active rheumatoid arthritis (RA) | ||
| 520 | |a METHODS: In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5, 10, or 30 mg or placebo once daily for 4 weeks to assess safety and tolerability. No safety signals precluded moving to Part B, where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5 mg (n = 63), 10 mg (n = 62), or 30 mg (n = 63), or placebo (n = 62) once daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary and secondary endpoints. Nonresponder imputation was used for missing data | ||
| 520 | |a RESULTS: After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. One hundred and eighty-nine (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (P > 0.05 for all comparisons). Five serious adverse events occurred (n = 2, placebo; n = 3, 30 mg); there was 1 death due to a fall | ||
| 520 | |a CONCLUSION: While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA | ||
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