Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis
Copyright © 2023 Walker, Adams, Guy, Chandrasekaran, Kinnersley, Ramesh, Zhang, Brown and Niranjan..
Background: Preliminary evidence for efficacy in pulmonary sarcoidosis has been shown for efzofitimod. Here we present supportive evidence of efficacy based on an exposure-response analysis. Methods: Data from two studies (Phase 1, N = 24, single dose in healthy volunteers, and Phase 1b/2a, N = 25, multiple doses over 24 weeks in participants with pulmonary sarcoidosis) were used to build a population pharmacokinetic model. Using this model, the relationship between efzofitimod exposure and three prespecified efficacy parameters [mean daily oral corticosteroid (OCS) dose, percent-predicted forced vital capacity (ppFVC) and King's Sarcoidosis Questionnaire-Lung (KSQ-Lung) score] was explored. Linear regression described the relationship of efzofitimod exposure and OCS reduction, ppFVC and KSQ-Lung score. Logistic regression related efzofitimod exposure to the probability of achieving a minimal clinically important difference for ppFVC and KSQ-Lung score. Due to the small study size, trends (not statistical significance) in relationships are reported. Results: In patients with pulmonary sarcoidosis, as efzofitimod exposure increased, the mean daily OCS dose decreased, and ppFVC and KSQ-Lung score improved over baseline. The slope for all the endpoints by both linear and logistic regression showed an improving trend with increased exposure. Conclusion: These preliminary findings of a positive exposure-response across multiple efficacy endpoints support the claim that proof of concept has been established for the use of efzofitimod in pulmonary sarcoidosis. Clinical Trial Registration: clinicaltrials.gov, identifier NCT03824392.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in pharmacology - 14(2023) vom: 20., Seite 1258236 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Walker, Gennyne [VerfasserIn] |
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| Links: |
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| Themen: |
Efzofitimod |
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| Anmerkungen: |
Date Revised 20.10.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT03824392 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fphar.2023.1258236 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363472002 |
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| 520 | |a Copyright © 2023 Walker, Adams, Guy, Chandrasekaran, Kinnersley, Ramesh, Zhang, Brown and Niranjan. | ||
| 520 | |a Background: Preliminary evidence for efficacy in pulmonary sarcoidosis has been shown for efzofitimod. Here we present supportive evidence of efficacy based on an exposure-response analysis. Methods: Data from two studies (Phase 1, N = 24, single dose in healthy volunteers, and Phase 1b/2a, N = 25, multiple doses over 24 weeks in participants with pulmonary sarcoidosis) were used to build a population pharmacokinetic model. Using this model, the relationship between efzofitimod exposure and three prespecified efficacy parameters [mean daily oral corticosteroid (OCS) dose, percent-predicted forced vital capacity (ppFVC) and King's Sarcoidosis Questionnaire-Lung (KSQ-Lung) score] was explored. Linear regression described the relationship of efzofitimod exposure and OCS reduction, ppFVC and KSQ-Lung score. Logistic regression related efzofitimod exposure to the probability of achieving a minimal clinically important difference for ppFVC and KSQ-Lung score. Due to the small study size, trends (not statistical significance) in relationships are reported. Results: In patients with pulmonary sarcoidosis, as efzofitimod exposure increased, the mean daily OCS dose decreased, and ppFVC and KSQ-Lung score improved over baseline. The slope for all the endpoints by both linear and logistic regression showed an improving trend with increased exposure. Conclusion: These preliminary findings of a positive exposure-response across multiple efficacy endpoints support the claim that proof of concept has been established for the use of efzofitimod in pulmonary sarcoidosis. Clinical Trial Registration: clinicaltrials.gov, identifier NCT03824392 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a King’s Sarcoidosis Questionnaire-Lung | |
| 650 | 4 | |a efzofitimod | |
| 650 | 4 | |a exposure-response relationship | |
| 650 | 4 | |a forced vital capacity | |
| 650 | 4 | |a pulmonary sarcoidosis treatment | |
| 650 | 4 | |a steroid-sparing effect | |
| 700 | 1 | |a Adams, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Guy, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Chandrasekaran, Abhijeeth |e verfasserin |4 aut | |
| 700 | 1 | |a Kinnersley, Nelson |e verfasserin |4 aut | |
| 700 | 1 | |a Ramesh, Pavithra |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Fran |e verfasserin |4 aut | |
| 700 | 1 | |a Niranjan, Vis |e verfasserin |4 aut | |
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