Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn's disease (REMODEL-CD) : study protocol for a multicentre, open-label, pragmatic clinical trial in the USA
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
INTRODUCTION: The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring. In response, our team has developed a personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure. We hypothesise that a precision dosing strategy starting from induction and targeting dose-specific pharmacokinetic and pharmacodynamic endpoints throughout therapy will significantly improve outcomes compared with a conventional dosing strategy.
METHODS AND ANALYSIS: Conduct a clinical trial to assess rates of deep remission between Crohn's disease patients receiving infliximab with precision dosing (n=90) versus conventional care (n=90). Patients (age 6-22 years) will be recruited from 10 medical centres in the USA. Each centre has been selected to provide either precision dosing or conventional care dosing. Precision dosing includes the use of a clinical decision support tool (RoadMAB) from the start of infliximab to achieve specific (personalised) trough concentrations and specific pharmacodynamic targets (at doses 3, 4 and 6). Conventional care includes the use of a modified infliximab starting dose (5 or 7.5 mg/kg based on the pretreatment serum albumin) with a goal to achieve maintenance trough concentrations of 5-10 µg/mL. The primary endpoint is year 1 deep remission defined as a combination of clinical remission (paediatric Crohn's disease activity index<10 (child) or a Crohn's disease activity index<150 (adults)), off prednisone>8 weeks and endoscopic remission (simple endoscopic severity-Crohn's disease≤2).
ETHICS AND DISSEMINATION: ). The study protocol has been approved by the Cincinnati Children's Hospital Medical Centre Institutional Review Board. Study results will be disseminated in peer-reviewed journals and presented at scientific meetings.
TRIAL REGISTRATION NUMBER: NCT05660746.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
BMJ open - 14(2024), 3 vom: 25. März, Seite e077193 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Minar, Phillip Paul [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 30.03.2024 published: Electronic ClinicalTrials.gov: NCT05660746 Citation Status MEDLINE |
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| doi: |
10.1136/bmjopen-2023-077193 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Minar, Phillip Paul |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn's disease (REMODEL-CD) |b study protocol for a multicentre, open-label, pragmatic clinical trial in the USA |
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| 500 | |a ClinicalTrials.gov: NCT05660746 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a INTRODUCTION: The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring. In response, our team has developed a personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure. We hypothesise that a precision dosing strategy starting from induction and targeting dose-specific pharmacokinetic and pharmacodynamic endpoints throughout therapy will significantly improve outcomes compared with a conventional dosing strategy | ||
| 520 | |a METHODS AND ANALYSIS: Conduct a clinical trial to assess rates of deep remission between Crohn's disease patients receiving infliximab with precision dosing (n=90) versus conventional care (n=90). Patients (age 6-22 years) will be recruited from 10 medical centres in the USA. Each centre has been selected to provide either precision dosing or conventional care dosing. Precision dosing includes the use of a clinical decision support tool (RoadMAB) from the start of infliximab to achieve specific (personalised) trough concentrations and specific pharmacodynamic targets (at doses 3, 4 and 6). Conventional care includes the use of a modified infliximab starting dose (5 or 7.5 mg/kg based on the pretreatment serum albumin) with a goal to achieve maintenance trough concentrations of 5-10 µg/mL. The primary endpoint is year 1 deep remission defined as a combination of clinical remission (paediatric Crohn's disease activity index<10 (child) or a Crohn's disease activity index<150 (adults)), off prednisone>8 weeks and endoscopic remission (simple endoscopic severity-Crohn's disease≤2) | ||
| 520 | |a ETHICS AND DISSEMINATION: ). The study protocol has been approved by the Cincinnati Children's Hospital Medical Centre Institutional Review Board. Study results will be disseminated in peer-reviewed journals and presented at scientific meetings | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT05660746 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Inflammatory bowel disease | |
| 650 | 4 | |a Paediatric gastroenterology | |
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| 700 | 1 | |a Zhang, Nanhua |e verfasserin |4 aut | |
| 700 | 1 | |a Mizuno, Tomoyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Vinks, Alexander A |e verfasserin |4 aut | |
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