炎症性腸疾患におけるウステキヌマブとヴェドリズマブのモデルに基づいた精密投与 (MOVE-IT)
炎症性腸疾患におけるウステキヌマブとヴェドリズマブのモデルに基づいた精密投与（MIPD） - 独立したランダム化比較試験
The goal of this clinical trial is to investigate if dosage of Ustekinumab (UST) and Vedolizumab (VDZ) based on Model-Informed Precision Dosing (MIPD) is equally as efficient in keeping adults with Inflammatory Bowel Disease (IBD) in remission as management based on what the treating physician deems best. The main question is:
Is using pharmacokinetic-pharmacodynamic (PK-PD) models to predict the appropriate dose and dosing interval for VDZ and UST at least as effective as current practices in maintaining IBD remission.
As above mentioned the comparison-group is adults with IBD, treated with UST or VDZ, managed as the physician deems best.
Participants will:
Have blood and stool tests done, as well as answer a questionnaire 4th weekly Have their dosage frequency decided on either by the PK-model or as the physician deems best visit the clinic once every 24 weeks for checkups. Have an endoscopy done at completion of the study (if the disease is primarily located in the small intestine, MRI or capsule endoscopy will be used instead)
調査の概要
状態
詳細な説明
Patients will 4th weekly have their drug-concentration in blood measured (and if low, also antidrug antibodies). Hemoglobin, Albumin, CRP and white blood cell count will also be done, as well as a stool-sample for calprotectin measurement.
For the control group however, the clinicians and patients will be blinded for the results of the blood- and stool samples, and the samples for drug concentration will not get analyzed before end of study.
4th weekly they will also answer PRO2 questionnaire, as well as the VAS-F. 8th weekly they will in addition to above mentioned also answer the EQ-5D-5L questionnaire.
At inclusion, after 24 weeks, and at 48 weeks the patients will in addition to the above mentioned also answer the short IBDQ and WPAI questionnaires, as well as be seen in the outpatient clinic to obtain HBI or SCCAI score as applicable, as well as to document any changes in concomitant medication or diseases, and to register if any serious adverse events have presented.
At completion of the trial, patients will have a endoscopy done.
In one subprotocol, the investigators will include 20 patients from Odense to have an endoscopy at both inclusion and completion. Here they will also have biopsies taken from all segments of the colon, which will be stores in a biobank for future research.
In another subprotocol 20 patients will be included to have a intestinal ultrasound done at inclusion and completion.
In a biobank for future research the investigators will also store serum-samples, buffy coat, and stool samples collected at inclusion, after 24 and 48 weeks from all included patients.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究場所
-
-
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Aalborg、デンマーク、9000
- Dept. of Gastrointestinal Diseases
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Esbjerg、デンマーク、6700
- Dept. of Internal Medicin
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Hvidovre、デンマーク、2650
- Dept. of Gastrointestinal Diseases
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Nyborg、デンマーク、5800
- Dept. of medicine
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Odense、デンマーク、5000
- Dept. of Gastrointestinal Diseases
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Vejle、デンマーク、7100
- Dept. of Medicine
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Ulcerative colitis or Crohn's disease. Diagnosed, according to universally acknowledged criteria, a minimum of 3 months prior to inclusion
- Age ≥ 18
- Stable treatment with VDZ or UST for at least 3 months prior to inclusion
- Stable disease activity, mild activity is accepted, defined by fecal calprotectin ≤ 200, and a weighted PRO2 < 14 for CD or a PRO2 ≤3 for UC
- No change in medical therapy within 3 months prior to inclusion, as concomitant therapy with other immune suppressants is allowed (Azathioprine, 6-mercaptopurine, Methotrexate, 5-aminosalicylic acid)
- The patient must be able to understand patient information material
- The patient must be able to give informed written consent
Exclusion Criteria:
- Having a diagnose of indeterminate colitis
- Having a stoma or pouch
- Fistulizing disease being the primary reason for treatment with VDZ or UST
- Expected eminent change of therapy
- Expected need for surgical intervention within the coming 3 months
- Contraindication against continuing treatment with VDZ or UST, including prior acute or delayed infusion reaction to VDZ or UST
- Any active infection requiring parenteral treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
- Any condition which the responsible physician finds incompatible with participation in the study
- Patients unable to participate in the collection of symptoms scores
- Patients who are pregnant or nursing at time of inclusion
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Model-informed precision dosing of Vedolizumab/Ustekinumab
Patients will have blood- and stool samples collected, as well as date and time of drug administration every 4th week. All of these informations, in addition to some informations collected at inclusion, will be used in a PK-model to prescribe when the next dosage of drug should be administered to keep the patient in the therapeutic window. |
the pharmacokinetic model will include information about inflammatory parameters both in blood- and fecal samples, as well as weight, sex, previous treatments and drug concentration. |
|
介入なし：Dosing of Vedolizumab/Ustekinumab by physicians best clinical assessment
Patients will have blood- and stool samples collected every 4 weeks, but these will be blinded for the physicians. They are to be treated as regular patients, but will be seen every 24 weeks to collect clinical activity scores, register alterations in concomitant medication and possible serious adverse events. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The fraction of patients in steroid-free remission
時間枠：at the end of the observation period (48 weeks)
|
((for CD defined by PRO2 ≤ 4, for UC defined by PRO2 = 0) AND a fecal calprotectin ≤200) |
at the end of the observation period (48 weeks)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The fraction of the observation period (48 weeks) where the disease is in steroid-free remission
時間枠：this is registered every 4th week throughout the study duration of 48 weeks.
|
for CD defined by patient reported outcome 2 (PRO2) stool frequency <= 3 and abdominal pain < = 1, for UC defined by PRO2, number of abnormal stools for the patient, bleeding from the rectum = 0) AND a fecal calprotectin ≤ 200. |
this is registered every 4th week throughout the study duration of 48 weeks.
|
|
The financial costs associated with the two treatment strategies over the observation period (12 months)
時間枠：through study completion, an average of 48 weeks
|
expenditure on medicines (both expenditure on the purchase of medicines and expenditure on the administration of medicines), expenses for doctor visits / visits to a nurse, possibly expenses for hospitalization, possibly expenses for surgery, possibly expenses for sick leave and possibly expenses for early retirement. After end of study, the investigators will collect data on sick leave etc. from the national patient registry. |
through study completion, an average of 48 weeks
|
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Endoscopic healing of the mucosa
時間枠：at completion of study, approximately 48 weeks
|
for CD assessed by Simple Endoscopic Score for Crohn's Disease (SES-CD) <3; and for UC assessed on the basis of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)≤1. If disease is primarily located in the small intestine, MRI or capsule endoscopy will be used instead, and assessed by the simplified MaRIA score <1 or Lewis score ≤135, respectively |
at completion of study, approximately 48 weeks
|
|
Changes in quality of life during the study period
時間枠：48 weeks
|
assessed by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) difference between baseline and end of study. Improvement of quality of life indicated by a positive change of the SIBDQ. SIBDQ is collected at inclusion, week 24 and week 48. A higher the score, indicates a better outcome, Maksimum score of 70 points. |
48 weeks
|
|
Quality of life as QALYs
時間枠：48 weeks
|
assessed by the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and converted to QALYs. The cost per QALY will also be calculated. EQ-5D-5L is collected every 8th week throughout the study. Score ranges from 5-25, a higher score indicating poorer quality of life. |
48 weeks
|
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Clinical Disease Activity
時間枠：48 weeks
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assessed by Simplified Clinical Colitis Activity Index (SCCAI) for UC and Harvey-Bradshaw Index (HBI) for CD. These are collected at inclusion and every 24th week thereafter. SCCAI score ranges from 0-19, a higher score indicating a more severe disease activity. HBI score ranges from 0-20, a higher score indicating more severe disease activity. |
48 weeks
|
|
Inflammatory burden over the observational period
時間枠：48 weeks
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CRP, albumin, hemoglobin, leukocyte counts and fecal calprotectin. These will be collected every 4th week |
48 weeks
|
|
Expenses for analysis of drug concentration
時間枠：48 weeks
|
patients will have drug concentrations analyzed every 4th week, the price of this will be collected |
48 weeks
|
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Expenses for drugs
時間枠：48 weeks
|
patients will typically administer sc VDZ every 4th to 2nd week, iv VDZ every 12th to 4th week and UST every 12th to 4th week |
48 weeks
|
|
Drug persistency
時間枠：48 weeks
|
number of patients switching to another treatment during the study |
48 weeks
|
|
Disease flares
時間枠：48 weeks
|
assessed by consumption of glucocorticoids or IBD-related surgery |
48 weeks
|
|
Fatigue
時間枠：48 weeks.
|
to assess if treating according to a PK-model results in less fatigue measured by Visual Analogue Scale to Evaluate Fatigue Severity (VAS-F). Patients are asked to register how fatigued they feel every 4th week throughout the study. The VAS-F is a visual analogue scale that goes from 0-10, 10 indicating severe fatigue. |
48 weeks.
|
|
Disease impact on work productivity and performance of daily activities
時間枠：48 weeks
|
Assessed by difference in Work Productivity and Activity Impairment questionnaire (WPAI) scores and changes in scores between patients in the intervention- and control group. WPAI is collected at inclusion and every 24th week throughout the study. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. |
48 weeks
|
協力者と研究者
捜査官
- 主任研究者：Mark A Ainsworth, professor, DMSc、Odense University Hospital
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 32844
- 2024-517123-39-00 (Ctis)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
De-identified individual participant data will possibly be shared, including clinical characteristics, laboratory test results, and patient-reported outcomes relevant to the study endpoints.
Data will be available after publication of the main trial results and completion of any relevant follow-up studies. This is expected to occur approximately one year after the study's primary completion date.
Data will be available for a minimum of 5 years following the publication of the trial results.
IPD 共有時間枠
will become available approximately March 2028 and will be available for at least 5 years
IPD 共有アクセス基準
Data will be shared with qualified researchers conducting legitimate scientific inquiries, particularly those working within the field of inflammatory bowel disease (IBD) and therapeutic drug monitoring (TDM)
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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