Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the rapidity of onset of clinical response to adalimumab therapy in patients with luminal Crohn's disease.

Official Title
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Rapidity of Onset of Response to Adalimumab in Luminal Crohn's Disease (RAPIDA Study)

Conditions
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Moderate to Severe Crohn's Disease

Intervention / Treatment
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* Biological: adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Crohn's disease (CD) diagnosed within, at least, the previous 4 months. Patients with active luminal (Harvey-Bradshaw Index [HBI] ≥ 8) moderate to- severe CD. No response to a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant. If receiving any of the following treatments, their dose should be stable during the periods indicated: Aminosalicylates for, at least, the last 4 weeks Probiotics for, at least, the last 4 weeks Analgesics for, at least, the last 4 weeks Antidiarrheals for, at least, the last 4 weeks CD-related antibiotics for, at least, the last 4 weeks Azathioprine, 6-mercaptopurine or methotrexate for, at least, the last 12 weeks If receiving any of the following treatments, their dose should not have been increase in the past two weeks (the dose reduction is permitted): Oral budesonide (maximum dose of 9 mg/day) Oral prednisone or equivalent (maximum dose of 40mg/day) Exclusion Criteria: Previous treatment with any anti-Tumor Necrosis Factor agent Surgical bowel resection within the previous 6 months, ostomy, extensive bowel resection (> 100 cm), short bowel syndrome Fistulising Crohn's disease Treatment with cyclosporine or tacrolimus within the previous 8 weeks Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure of worse than grade II New York criteria (New York Heart Association Functional Classification). Subject with an ostomy or ileoanal pouch, proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis (Subjects with a previous ileo-rectal anastomosis are not excluded). Screening laboratory values (according to central laboratory) Known hepatitis C (HC) infection. Serologic evidence of hepatitis B (HB) infection based on the results of testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) antibodies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab<br>Participants received adalimumab for 12 weeks (160 mg at Week 0; 80 mg at week 2; then adalimumab 40 mg every other week starting at Week 4). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira, ABT-D2E7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at Day 4 | Clinical response defined as a decrease of at least 3 points in Harvey-Bradshaw Index (HBI) score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease. | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at Week 1 | Clinical response defined as a decrease of at least 3 points in HBI score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease. | Week 1 | 
| Percentage of Participants With Clinical Remission at Weeks 2 and 4 | Clinical remission defined as HBI < 5. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease. | Weeks 2 and 4 | 
| European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Index Score: Change From Baseline to Week 12 | The EQ-5D-3L is a standardized instrument for use as a measure of health-related quality of life (HRQoL) and consists of 2 components: The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. The EQ-5D visual analog scale (VAS) is a 20-cm scale with endpoints labeled best imaginable health and worst imaginable health anchored at 100 and 0, respectively. A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L Index Score are presented. | Baseline (Week 0) and Week 12 | 
| European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Visual Analog Scale (VAS): Change From Baseline to Week 12 | The EQ-5D-3L is a standardized instrument for use as a measure of HRQoL and consists of 2 components: The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. The EQ-5D VAS is a 20-cm scale with endpoints labeled best imaginable health and worst imaginable health anchored at 100 and 0, respectively. A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented. | Baseline (Week 0) and Week 12 | 
| Inflammatory Bowel Disease Quality-36 (IBDQ-36) Questionnaire Overall Score: Change From Baseline to Week 12 | The IBDQ-36 is used to assess the HRQoL related to bowel symptoms. The IBDQ-36 overall score is calculated as the sum of thirty-six items, each scored on a 1 to 7 likert point scale, and ranges from 7 to 252. The highest score indicates the best HRQoL related to bowel symptoms. A positive change in IBDQ-36 overall score indicates an improvement in HRQoL due to inflammatory bowel disease. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented. | Baseline (Week 0) and Week 12 | 
| Fatigue Impact Scale for Daily Use (D-FIS): Change From Baseline to Week 12 | The D-FIS is used to measure the impact of fatigue on the daily lives of persons. The D-FIS overall score was calculated as the sum of eight items, each scored on a 0 to 4 point scale, and ranges from 0 to 32. A higher score indicates a higher impact of fatigue on daily life. A negative change in D-FIS Overall Score means an improvement in HRQoL due to fatigue. Mean Baseline and mean change from Baseline to Week 12 are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hemoglobin | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and coagulation (activated partial thromboplastin time [aPTT], international normalized ratio [INR], and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hematocrit | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Erythrocytes | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Sedimentation Rate (ESR) | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: C-reactive Protein (CRP) | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fecal Calprotectin | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Activated Partial Thromboplastin Time (aPTT) | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: International Normalized Ratio (INR) | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fibrinogen | Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented. | Baseline (Week 0) and Week 12 | 
| Percentage of Participants With Clinical Response at Day 4 or Week 12 and Clinical Remission at Week 12 | The percentage of participants with clinical response (defined as decrease of at least 3 points in HBI score) at Day 4 or Week 1 and clinical remission (defined as a HBI < 5) at Week 12. | Up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease