Assessment of Mucosal Activity to Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants (ADACAL)
cAlprotectin and hsCRP as Markers of a New Diagnostic-therapeutic strAtegy That Assesses muCosal Activity to individuaLize Treatment and Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants
調査の概要
詳細な説明
Patients will be prescreened for inclusion criteria one week before the start of screening at Visit 0 (Prescreening Visit). Patients must be on stable doses of azathioprine/mercaptopurine. Patients will be given a diary to record their CD symptoms for the seven days prior to Visit 1. At Visit 1 (Screening Visit 1), patients will have their CDAI score assessed based upon their diary information. Patients with CDAI ≤ 220 will then have both calprotectin and hsCRP testing done. Patients with calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L will be notified and told to schedule Visit 2 within three weeks. At Visit 2 (Screening Visit 2), patients will undergo a colonoscopy. A Crohn's Disease Endoscopic Index of Severity (CDEIS) will be used to determine the endoscopic activity. Patients with significant endoscopic lesions will be notified and asked to enroll in the study.
Patients will be randomized into the study at Visit 3 (Randomization Visit, same day of Visit 2 in results available). Due to the cost and invasiveness of the colonoscopy, the Screening Visit 2 colonoscopy will serve as the baseline for the study, should the patient be enrolled. Drug will also be dispensed at this visit. Eligible patients will be randomized in a 1:1 ratio to receive either adalimumab or placebo during the treatment period, along with continuing their current immunosuppressive maintenance treatment at a stable dose. Treatment in both arms will be induction at 160/80mg and maintenance on 40 mg every other week.
Patients will return for follow up visits every 12 weeks until the final follow-up visit at 48 weeks (Visit 7), where another colonoscopy will be performed. Patients who terminate early from the study for any reason will be asked to return for a follow-up visit, where Visit 7 procedures will be performed.
Before week 48, if a patient has an increase of more than 50% in either calprotectin and/or hsCRP over baseline and above the thresholds at any regular visit, a follow-up visit will be performed two weeks later. If the 50% increase is still observed another colonoscopy will be performed, within two weeks of the follow-up visit. If patients still have significant endoscopic lesions, study product will be intensified to 40 mg weekly. This will include patients on placebo in order to preserve the double-blind aspect of the study.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Barcelona、スペイン、08025
- Hospital Santa Creu i Sant Pau
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Madrid、スペイン、28034
- Hospital Ramon y Cajal
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Madrid、スペイン、28007
- Hospital Gregorio Marañón
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Madrid、スペイン、28005
- Hospital Universitario La Princesa
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Sevilla、スペイン、41013
- Hospital Virgen del Rocío
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Valencia、スペイン、46010
- Hospital Clinico de Valencia
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Zaragoza、スペイン
- Hospital Lozano Blesa
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A coruña
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Santiago de Compostela、A coruña、スペイン
- Complejo Hospitalario Santiago de Compostela
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Andalucía
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Córdoba、Andalucía、スペイン、14004
- Hospital Universitario Reina Sofia
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Barcelona
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Badalona、Barcelona、スペイン
- Hospital Germans Trias i Pujol
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Canarias
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Las Palmas de Gran Canarias、Canarias、スペイン、35010
- Hospital Doctor Negrin
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Valencia
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Manises、Valencia、スペイン、46940
- Hospital de Manises
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Amiens、フランス、80054
- CHU Amiens - Hospital Nord
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Clichy、フランス、92110
- Hospital Beaujon
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Lille、フランス、59037
- CHRU Lille - Hospital Claude Huriez
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Lyon、フランス、69495
- CHU Lyon Sud
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Nantes、フランス、44093
- CHU Nantes
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Paris、フランス、75010
- Hospital Saint Louis
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Reims、フランス、51092
- CHRU Reims - Hospital Robert Debre
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Rouen、フランス、76031
- CHU Rouen - Hospital Charles Nicolle
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Saint Etienne、フランス、42270
- CH Saint Etienne - Hospital Nord
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Bordeaux
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Pessac、Bordeaux、フランス、33604
- CHU Bordeaux - Hospital Haut-Leveque
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Nancy
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Vandoeuvre Les Nancy、Nancy、フランス、54500
- CHU Nancy - Hospital de Brabois Adultes
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Tours
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Chambray、Tours、フランス、76031
- CHU TOURS - Hospital Trousseau
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Bonheiden、ベルギー、2820
- Imeldaziekenhuis Bonheiden
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Bruxelles、ベルギー、1070
- Hospital Erasme Bruxelles
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Bruxelles、ベルギー、1200
- Hospital Saint Luc Bruxelles
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Gent、ベルギー、9000
- Hospital University Gent
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Liege、ベルギー、4000
- Centre Hospitalier Universitaire de Liege
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Roeselare、ベルギー、8800
- Heiling Hartzieknhuis Roeselare
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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:
- Age 18-75 years old- Patients with CD diagnosis confirmed by colonoscopy
- Patients with inflammatory CD of terminal ileal, colonic or ileocolonic location
- Maintenance treatment with at least 2 mg/kg/day for azathioprine/ 1 mg/kg/day for mercaptopurine or the highest dosage tolerated in patients who could not tolerate this dosage, at least 6 months.
- Willingness to sign informed consent
- If female of childbearing age, be post-menopausal, surgically sterile, or willing to use a reliable form of birth control for the duration of the study (such as physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device)and for at least five months after the last adalimumab treatment.
- Able to comply with the requirements of the study.
- CDAI score ≤ 220.
- Calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L.
- Significant lesions seen during colonoscopy, as defined by CDEIS.
Exclusion Criteria:
- Patients with an ostomy, or ileoanal pouch (subject with previous ileo-rectal anastomosis are not excluded), draining fistula, abscess
- Patients who had intestinal resection within one year.
- Symptomatic stricture either diagnosed by colonoscopy or clinically suspected and confirmed by imaging techniques.
- Prior treatment with any anti-tumor necrosis factor (TNF) drug.
- Patients receiving rectal treatment 1 month before inclusion
- Signs of active infection
- Previous history of active untreated or inadequately treated tuberculosis (TB) or latent TB. Patients should be screened for latent TB as per local guidelines or clinical practice in the country of study conduct. Patients with latent TB should be treated with standard antimycobacterial therapy (for at least 4 weeks) before initiating biologic therapy and have a negative CRX for active TB at screening
- Subjects with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), recent cerebrovascular accident, or any other condition which, in the opinion of the Investigator or the sponsor, would put the subject at risk by participation in the protocol
- Signs of colon cancer or dysplasia
- Signs of severe or unstable renal, hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, or hematological disease
- Signs of cancer in the past five years, except for localized and treated basal cell skin cancer or cervical cancer
- Patients who are pregnant or nursing
Concomitant treatment with:
- Live vaccines.
- 5-ASA compounds: Rectal 5-ASA should be discontinued at least 4 weeks before study inclusion. Oral 5-ASA must be at a stable dose for at least 4 weeks before study inclusion. If oral 5-ASA has recently been discontinued, 4 weeks should pass before study inclusion.
- Oral corticosteroids (eg., Prednisone, budesonide) should be discontinued for 3 months before study inclusion.
- Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
- Immunomodulators:
Patients receiving therapy with azathioprine/mercaptopurine must have been on a stable dose for at least 12 weeks before inclusion and must continue with the same dose during the study.
No treatment with other known immunomodulators (eg. methotrexate, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, ustekinumab, pentoxifylline, or mycophenolate mofetil) or experimental drugs (eg., factor colony stimulating granulocyte macrophage [GM-CSF]) within 6 months
- Monoclonal antibodies or anti-TNF drugs.
Aspirin or Non-steroidal anti-inflammatory drugs (NSAIDs). Treatment with aspirin and/or NSAIDS should not occur for more than 15 consecutive days before collecting of the stool sample for Calprotectin and performing the colonoscopy.
- Screening laboratory and other analyses show any of the following abnormal results:
- Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 x the upper limit of the reference range;
- Total bilirubin ≥ 3 mg/dL (51 μmol/L);
Serum creatinine > 1.6 mg/dL (144 μmol/L)
- History of any drug or alcohol abuse in the past 2 years
- Receipt of other study product within 3 months of inclusion in this study
- Patients employed by the sponsor or in any relationship of dependence with the sponsor and/or investigator
- Staff at the study center
- Hypersensitivity to the active substance or to any of the excipients
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:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター:PLACEBO
Treatment with placebo
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PLACEBO at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48.
If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier.
If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly
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アクティブコンパレータ:ADALIMUMAB
Treatment with Adalimumab
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Adalimumab at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48.
If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier.
If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly.
他の名前:
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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 |
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The primary efficacy endpoint is the rate of therapeutic failure up to week 48
時間枠:Every 12 weeks up to Week 48
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The therapeutic failure is defined as any of following cases:
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Every 12 weeks up to Week 48
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
The rate of therapeutic failure (see the definition of primary endpoint) up to week 24
時間枠:up to week 24
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up to week 24
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Change in CDEIS from baseline to week 48
時間枠:up to week 48
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CDEIS = Crohn's Disease Endoscopic Index of Severity.
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up to week 48
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The rate of mucosal healing (CDEIS=0) at week 48
時間枠:at week 48
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CDEIS = Crohn's Disease Endoscopic Index of Severity
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at week 48
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The rate of CDEIS remission (CDEIS<=3) at week 48
時間枠:at week 48
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CDEIS = Crohn's Disease Endoscopic Index of Severity
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at week 48
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The rate of CDEIS response, which is defined as a decrease of at least 4 points in CDEIS from baseline to week 48
時間枠:from baseline up to week 48
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CDEIS = Crohn's Disease Endoscopic Index of Severity
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from baseline up to week 48
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Change in CDAI from baseline to week 12, 24, 36 and 48
時間枠:from baseline to week 12, 24, 36 and 48
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CDAI = Crohn's Disease Activity Index.
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from baseline to week 12, 24, 36 and 48
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Change in the global score based on IBDQ from baseline to week 12, 24, 36, and 48.
時間枠:from baseline to week 12, 24, 36, and 48.
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IBDQ = Inflammatory Bowel Disease Questionnaire.
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from baseline to week 12, 24, 36, and 48.
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Area Under the Curve (AUC) over 48 weeks for CDAI
時間枠:48 weeks
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48 weeks
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The number of surgical interventions related to CD up to 24 and 48 weeks
時間枠:up to 24 and 48 weeks
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up to 24 and 48 weeks
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The rate of hospital admissions related to the disease, to the treatment side effects or other causes up to weeks 24 or 48
時間枠:up to weeks 24 or 48
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up to weeks 24 or 48
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The rate of serious AEs between the two strategies up to 24 and 48 weeks
時間枠:up to 24 and 48 weeks
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up to 24 and 48 weeks
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The rate of serious AEs requiring the cessation of the ongoing treatment between the two strategies up to 24 and 48 weeks.
時間枠:up to 24 and 48 weeks
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up to 24 and 48 weeks
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The accuracy of calprotectin/hsCRP to predict therapeutic failure 12 weeks in advance
時間枠:12 weeks
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12 weeks
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The correlation between calprotectin, hsCRP and CDAI at any time points during the study.
時間枠:48 weeks
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Pearson Product-Moment Correlation will be used to evaluate correlations between calprotectin, hsCRP and CDAI at all scheduled visits.
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48 weeks
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The correlation between calprotectin/hsCRP and CDEIS or mucosal healing at Baseline and Week 48.
時間枠:at Baseline and Week 48.
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Pearson Product-Moment Correlation will also be used to evaluate between calprotectin (and hsCRP) and CDEIS at Baseline and Week 48.
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at Baseline and Week 48.
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Change in the scores based on WPAI from baseline to week 12, 24, 36 and 48
時間枠:from baseline to week 12, 24, 36 and 48
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WPAI = Work Productivity and Activity Impairment Questionnaire
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from baseline to week 12, 24, 36 and 48
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The change in calprotectin and hsCRP from baseline to week 12, 24, 36, and 48
時間枠:from baseline to week 12, 24, 36, and 48
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from baseline to week 12, 24, 36, and 48
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協力者と研究者
捜査官
- 主任研究者:VALLE GARCÍA, MD、Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
クローン病の臨床試験
-
Adelphi Values LLCBlueprint Medicines Corporation完了肥満細胞性白血病 (MCL) | 攻撃的な全身性肥満細胞症 (ASM) | SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD) | くすぶり全身性肥満細胞症 (SSM) | 無痛性全身性肥満細胞症 (ISM) ISM サブグループが完全に募集されましたアメリカ
Placeboの臨床試験
-
Palacky University完了
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Universidade Federal do ParaConselho Nacional de Desenvolvimento Científico e Tecnológico完了
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Advice Pharma Group srl積極的、募集していない肥満 | 栄養障害 | 体重 | 減量 | 食生活 | 太りすぎと肥満 | 健康行動 | ダイエット、健康 | ダイエット習慣 | ライフスタイル | 栄養、健康 | 行動障害イタリア
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University Hospital, Strasbourg, France積極的、募集していない