Study of Adalimumab Treatment for Induction and Maintenance of Clinical Remission in Subjects With Crohn's Disease
- Conditions
- Crohn's Disease
- Interventions
- Biological: adalimumab
- Registration Number
- NCT00409617
- Lead Sponsor
- Abbott
- Brief Summary
The purpose of this study is to evaluate the safety of adalimumab for treatment of patients with moderate to severe Crohn's Disease (CD) and to measure the effects of treatment on patient general well-being, health-related quality of life (QoL), fistula healing, CD-related extra-intestinal manifestations, work performance, and overall activity.
- Detailed Description
This is an open-label, multi-center, study designed to evaluate the safety and efficacy of adalimumab on inducing and maintaining clinical remission in subjects with moderate to severe Crohn's Disease.
Approximately 1000 subjects with a diagnosis of moderate to severe Crohn's Disease (Harvey Bradshaw Index score \>= 7) will be enrolled at approximately 200 sites within Europe. Enrollment will be dependent on meeting all screening criteria.
Study medication will be administered by subcutaneous injection. At Baseline (Week 0), all subjects will receive a dose of 160 mg adalimumab. At Week 2, all subjects will receive a dose of 80 mg adalimumab. Starting at Week 4, all subjects will begin receiving injections of adalimumab 40 mg every other week and will continue every other week dosing through Week 20 except in the case of disease flare or non-response.
Starting at Week 12, subjects who experience a disease flare (flare is defined by an increase in the Harvey Bradshaw Index \>=3 and a total Index score of \>=7 when compared to Week 4) or are not responding to adalimumab treatment (non-response is defined as a decrease in the Harvey Bradshaw Index by fewer than 3 points compared to Baseline) will be permitted to increase study therapy to adalimumab 40 mg every week.
If the subject continues to demonstrate a lack of improvement on every week adalimumab therapy, they may be withdrawn from the study.
Prior to Week 8 subjects will not be allowed to increase or decrease Crohn's specific concomitant medications except in the event of concomitant Crohn's treatment-related toxicities assessed as moderate to severe. Changes in concomitant medications at/after Week 8 will be at the Investigator's discretion.
Subjects will be evaluated for safety and efficacy at Baseline (Week 0), Weeks 2, 4, 8, 12, and 20, and at unscheduled visits. Efficacy evaluations include HBI, Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Work Productivity Activity Index (WPAI) questionnaire, fistula counts, health care resource utilization (HCRU), and evaluation of CD-related extra-intestinal manifestations (EIMs). Safety assessments include vital signs, physical examination, general laboratory analyses, urinalysis, and monitoring of adverse events (AEs).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 945
- Diagnosis of moderate to severe Crohn's Disease confirmed by endoscopy or radiologic evaluation for greater than 4 months (16 weeks)
- Inadequate response to conventional therapy for Crohn's Disease
- Subjects >=18 and <=75 years of age and in good health (Investigator discretion) with a recent stable medical history
- Harvey Bradshaw Index score of 7 or higher
- Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
- Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study
- Female subject who is pregnant or breast-feeding or considering becoming pregnant
- Previous treatment with adalimumab or previous participation in an adalimumab clinical study
- Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
- Subjects with any prior exposure to Tysabri® (natalizumab)
- Subjects on prednisone >40 mg/day (or equivalent), subjects on budesonide >9 mg/day, or subjects who are taking prednisone and budesonide concurrently at Baseline
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Open Label adalimumab -
- Primary Outcome Measures
Name Time Method Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5. Week 20 of treatment 5-items that assess general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Score is total of 1) subject well-being (0=very well; 4=terrible); 2) abdominal pain (0=none; 3=severe); 3) diarrhea (number of time per day); 4) abdominal mass (0=none; 3=definite and tender); 5) complications (number). Maximum total score for HBI is not specified, is dependent on number of diarrhea times each day and number of complications. Clinical remission = HBI less than 5. Highest total score at Baseline was 47. Missing data were imputed using non-responder imputation (NRI).
- Secondary Outcome Measures
Name Time Method Number of Participants Who Were Responders at Week 20 of Treatment. A Responder Was Defined as a Participant Who Had a Decrease of 3 or More on the HBI. Week 20 of treatment 5-items that assess general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Score is total of 1) subject well-being (0=very well; 4=terrible); 2) abdominal pain (0=none; 3=severe); 3) diarrhea (number of time per day); 4) abdominal mass (0=none; 3=definite and tender); 5) complications (number). Participants who had a decrease from Baseline of at least 3 points in HBI total score were considered responders. Missing data were imputed using non-responder imputation (NRI).
Number of Participants Who Had a Reduction in Number of Draining Fistulas of at Least 50% From Baseline to Week 20 Week 20 of treatment A count of the number of cutaneous fistulas draining was performed during each physical examination. Among participants who had draining fistulas at Baseline, the number of participants who had a reduction in the number of draining fistulas of at least 50% from Baseline to Week 20 of treatment was determined. Fistulas were classified as abdominal or perianal.
Number of Participants Who Had Extra-intestinal Manifestations (EIM) at Baseline and Resolution by Week 20. Week 20 of treatment Number of participants who had EIM at baseline and had resolution of those manifestations at Week 20. EIM were skin lesions, eye lesions, joint complaints, CD-related hepatic disease, thrombosis, and nephrolithiasis. EIMs were determined by physical examination.
Mean Change in Total Score of Short Inflammatory Bowel Disease Questionnaire (SIBDQ) From Baseline to Week 20 Week 20 of treatment 10-item assessment of health-related quality of life (QoL) in patients with inflammatory bowel disease. Participant marks an option from 1 to 7 for each item. For some items, 1=None of the time; for other items, 1=All of the time. Value for all items are summed. Total score=10 to 70; a high score=good quality of life (QoL). An increase in score indicates improvement. An absolute change in the SIBDQ score of 9 is considered a minimum clinically important difference (MCID) for a patient.
Mean Change in Percent Work Time Missed Due to Crohn's Disease From Baseline to Week 20 of Treatment Week 20 of treatment Percent Work Time Missed (Absenteeism) due to CD is one component of the Work Productivity and Activity Impairment (WPAI) Questionnaire. Score of 0% = no impairment. A decrease in the mean indicates improvement.
Mean Change in Percent Impairment While Working From Baseline to Week 20 of Treatment Week 20 of treatment Percent impairment while working is a component of the Work Productivity and Activity Impairment measure. A score of 0% = no impairment. A decrease in mean score indicates lessening of impairment.
Mean Change in Overall Work Productivity and Activity Impairment Score From Baseline to Week 20 Week 20 of treatment 6-items that assess impairment in work productivity and daily activity during the 7 days before the assessment. It measures the percentage of overall impairment in work productivity and daily activity due to CD. A WPAI score of 0% = no impairment and a score of 100% = total loss of work productivity or activity. An absolute change in WPAI score of 7% is considered the minimum clinically important difference (MCID).
Mean Change in Activity Impairment Score From Baseline to Week 20 Week 20 of treatment Daily activity is one component of the Work Productivity and Activity Impairment Questionnaire. 0% = no impairment. A decrease in the mean indicates improvement.
Trial Locations
- Locations (189)
Site Ref # / Investigator 3623
🇫🇮Hyvinkaa, Finland
Site Ref # / Investigator 3325
🇮🇪Dublin 24, Ireland
Site Ref # / Investigator 3324
🇮🇪Dublin 9, Ireland
Site Ref # / Investigator 3630
🇳🇴Hamar, Norway
Site Ref # / Investigator 3069
🇵🇹Coimbra, Portugal
Site Ref # / Investigator 3037
🇩🇰Aarhus C, Denmark
Site Ref # / Investigator 3088
🇩🇰Helsingor, Denmark
Site Ref # / Investigator 3019
🇩🇰Odense C, Denmark
Site Ref # / Investigator 3013
🇫🇷Reims, France
Site Ref # / Investigator 3024
🇫🇷Rouen, France
Site Ref # / Investigator 3018
🇫🇷Vandoeuvre Les Nancy, France
Site Ref # / Investigator 3045
🇩🇪Stuttgart, Germany
Site Ref # / Investigator 3089
🇩🇪Berlin, Germany
Site Ref # / Investigator 3092
🇩🇪Frankfurt, Germany
Site Ref # / Investigator 4606
🇬🇷Heraklion, Greece
Site Ref # / Investigator 3098
🇩🇪Munich, Germany
Site Ref # / Investigator 3091
🇩🇪Luebeck, Germany
Site Ref # / Investigator 3072
🇩🇪Heidelberg, Germany
Site Ref # / Investigator 3049
🇩🇪Mainz, Germany
Site Ref # / Investigator 3014
🇫🇷Nantes, France
Site Ref # / Investigator 2973
🇫🇷Strasbourg, France
Site Ref # / Investigator 3081
🇩🇪Hannover, Germany
Site Ref # / Investigator 3326
🇮🇪Cork, Ireland
Site Ref # / Investigator 4358
🇬🇷Athens, Greece
Site Ref # / Investigator 3368
🇩🇪Dueren, Germany
Site Ref # / Investigator 3086
🇩🇪Braunschweig, Germany
Site Ref # / Investigator 3033
🇫🇷Creteil, France
Site Ref # / Investigator 3055
🇩🇪Munich, Germany
Site Ref # / Investigator 3056
🇩🇪Muenster, Germany
Site Ref # / Investigator 3030
🇫🇷Creteil, France
Site Ref # / Investigator 3046
🇩🇪Osnabrueck, Germany
Site Ref # / Investigator 3034
🇩🇪Karlsruhe, Germany
Site Ref # / Investigator 3625
🇧🇪Ghent, Belgium
Site Ref # / Investigator 3953
🇮🇹Bologna, Italy
Site Ref # / Investigator 3017
🇫🇷Paris, France
Site Ref # / Investigator 4352
🇬🇷Athens, Greece
Site Ref # / Investigator 3071
🇩🇪Leipzig, Germany
Site Ref # / Investigator 3090
🇩🇪Magdeburg, Germany
Site Ref # / Investigator 3083
🇩🇪Mainz, Germany
Site Ref # / Investigator 3095
🇩🇪Rostock, Germany
Site Ref # / Investigator 3025
🇫🇷Paris Cedex 10, France
Site Ref # / Investigator 3015
🇫🇷Clichy, France
Site Ref # / Investigator 3031
🇫🇷Marseilles, France
Site Ref # / Investigator 4357
🇬🇷Athens, Greece
Site Ref # / Investigator 4359
🇬🇷Thessaloniki, Greece
Site Ref # / Investigator 4351
🇬🇷Thessaloniki, Greece
Site Ref # / Investigator 3096
🇩🇪Berlin, Germany
Site Ref # / Investigator 2980
🇩🇪Berlin, Germany
Site Ref # / Investigator 3094
🇩🇪Cottbus, Germany
Site Ref # / Investigator 2970
🇩🇪Rottenburg, Germany
Site Ref # / Investigator 2969
🇩🇪Augsburg, Germany
Site Ref # / Investigator 3027
🇫🇷Evry, France
Site Ref # / Investigator 2995
🇫🇷Paris, France
Site Ref # / Investigator 3011
🇫🇷Colombes, France
Site Ref # / Investigator 3048
🇫🇷Grenoble, France
Site Ref # / Investigator 2977
🇦🇹Wels, Austria
Site Ref # / Investigator 2981
🇩🇪Hamburg, Germany
Site Ref # / Investigator 3080
🇩🇪Jena, Germany
Site Ref # / Investigator 3066
🇩🇪Halle, Germany
Site Ref # / Investigator 3040
🇩🇪Freiburg, Germany
Site Ref # / Investigator 4355
🇬🇷Ioannina, Greece
Site Ref # / Investigator 4353
🇬🇷Nikaia, Greece
Site Ref # / Investigator 3061
🇮🇹Florence, Italy
Site Ref # / Investigator 3629
🇳🇴Bodo, Norway
Site Ref # / Investigator 3035
🇮🇹Milan, Italy
Site Ref # / Investigator 3065
🇮🇹Naples, Italy
Site Ref # / Investigator 3064
🇮🇹Rome, Italy
Site Ref # / Investigator 3620
🇳🇴Oslo, Norway
Site Ref # / Investigator 3596
🇵🇹Braga, Portugal
Site Ref # / Investigator 3493
🇸🇰Bratislava, Slovakia
Site Ref # / Investigator 3062
🇮🇹Palermo, Italy
Site Ref # / Investigator 3063
🇮🇹Pavia, Italy
Site Ref # / Investigator 3058
🇮🇹Pescara, Italy
Site Ref # / Investigator 2991
🇮🇹Rome, Italy
Site Ref # / Investigator 2990
🇪🇸Barcelona, Spain
Site Ref # / Investigator 3039
🇮🇹Rome, Italy
Site Ref # / Investigator 3087
🇮🇹Rozzano, Italy
Site Ref # / Investigator 3038
🇮🇹San Donato Milanese, Italy
Site Ref # / Investigator 2998
🇪🇸Cabuenes-Gijon, Spain
Site Ref # / Investigator 3448
🇪🇸Alicante, Spain
Site Ref # / Investigator 3005
🇪🇸Barakaldo, Spain
Site Ref # / Investigator 3000
🇪🇸Santander, Spain
Site Ref # / Investigator 3007
🇪🇸Zaragoza, Spain
Site Ref # / Investigator 4581
🇬🇧Surrey, United Kingdom
Site Ref # / Investigator 3029
🇫🇷Nice, France
Site Ref # / Investigator 2994
🇫🇷Montpellier, France
Site Ref # / Investigator 4275
🇫🇷Paris, France
Site Ref # / Investigator 3084
🇩🇪Bochum, Germany
Site Ref # / Investigator 3097
🇫🇷Lille Cedex, France
Site Ref # / Investigator 3016
🇫🇷Paris, France
Site Ref # / Investigator 3041
🇩🇪Berlin, Germany
Site Ref # / Investigator 3070
🇩🇪Berlin, Germany
Site Ref # / Investigator 2985
🇫🇷Montfermeil, France
Site Ref # / Investigator 2996
🇫🇷Paris, France
Site Ref # / Investigator 3082
🇩🇪Hamburg, Germany
Site Ref # / Investigator 3078
🇩🇪Regensburg, Germany
Site Ref # / Investigator 2974
🇫🇷Pierre Benite, France
Site Ref # / Investigator 2986
🇫🇷Toulouse, France
Site Ref # / Investigator 3053
🇩🇪Dresden, Germany
Site Ref # / Investigator 3051
🇩🇪Bochum, Germany
Site Ref # / Investigator 3079
🇩🇪Stuttgart, Germany
Site Ref # / Investigator 2972
🇩🇪Dachau, Germany
Site Ref # / Investigator 3052
🇩🇪Erlangen, Germany
Site Ref # / Investigator 3093
🇩🇪Herne, Germany
Site Ref # / Investigator 3085
🇩🇪Essen, Germany
Site Ref # / Investigator 3044
🇩🇪Hamburg, Germany
Site Ref # / Investigator 2979
🇩🇪Hamburg, Germany
Site Ref # / Investigator 2989
🇪🇸Barcelona, Spain
Site Ref # / Investigator 3043
🇩🇪Hamburg, Germany
Site Ref # / Investigator 3617
🇩🇪Kiel, Germany
Site Ref # / Investigator 3054
🇩🇪Munich, Germany
Site Ref # / Investigator 3073
🇩🇪Mannheim, Germany
Site Ref # / Investigator 3042
🇩🇪Stade, Germany
Site Ref # / Investigator 3010
🇪🇸Zaragoza, Spain
Site Ref # / Investigator 2978
🇦🇹Vienna, Austria
Site Ref # / Investigator 3077
🇦🇹Graz, Austria
Site Ref # / Investigator 2975
🇦🇹Vienna, Austria
Site Ref # / Investigator 2976
🇦🇹Vienna, Austria
Site Ref # / Investigator 3021
🇧🇪Brussels, Belgium
Site Ref # / Investigator 2983
🇫🇷Bethune, France
Site Ref # / Investigator 3022
🇧🇪Liege, Belgium
Site Ref # / Investigator 4659
🇨🇿Prague 7, Czech Republic
Site Ref # / Investigator 3075
🇩🇰Aalborg, Denmark
Site Ref # / Investigator 3047
🇧🇪Roeselare, Belgium
Site Ref # / Investigator 3893
🇨🇿Brno, Czech Republic
Site Ref # / Investigator 4660
🇨🇿Prague 5, Czech Republic
Site Ref # / Investigator 4657
🇨🇿Olomouc, Czech Republic
Site Ref # / Investigator 3076
🇩🇰Hvidovre, Denmark
Site Ref # / Investigator 3012
🇫🇷Besancon, France
Site Ref # / Investigator 3032
🇫🇷Amiens, France
Site Ref # / Investigator 2982
🇫🇷Caen, France
Site Ref # / Investigator 2993
🇫🇷Bordeaux, France
Site Ref # / Investigator 3026
🇫🇷Pessac Cedex, France
Site Ref # / Investigator 3050
🇩🇪Minden, Germany
Site Ref # / Investigator 3057
🇩🇪Muenster, Germany
Site Ref # / Investigator 3036
🇮🇹Padova, Italy
Site Ref # / Investigator 3009
🇪🇸Badalona - Barcelona, Spain
Site Ref # / Investigator 4626
🇸🇰Kosice, Slovakia
Site Ref # / Investigator 3002
🇪🇸Barcelona, Spain
Site Ref # / Investigator 2988
🇪🇸Galdakano, Spain
Site Ref # / Investigator 3486
🇪🇸Barcelona, Spain
Site Ref # / Investigator 2997
🇪🇸Madrid, Spain
Site Ref # / Investigator 4383
🇪🇸Las Palmas de Gran Canaria, Spain
Site Ref # / Investigator 3484
🇪🇸Madrid, Spain
Site Ref # / Investigator 3595
🇪🇸Madrid, Spain
Site Ref # / Investigator 3003
🇪🇸Valencia, Spain
Site Ref # / Investigator 3008
🇪🇸Palma de Mallorca, Spain
Site Ref # / Investigator 3895
🇸🇪Gothenburg, Sweden
Site Ref # / Investigator 3488
🇸🇪Lund, Sweden
Site Ref # / Investigator 3499
🇸🇪Linkoping, Sweden
Site Ref # / Investigator 3500
🇸🇪Gothenburg, Sweden
Site Ref # / Investigator 3892
🇸🇪Oestersund, Sweden
Site Ref # / Investigator 3896
🇸🇪Stockholm, Sweden
Site Ref # / Investigator 3487
🇸🇪Stockholm, Sweden
Site Ref # / Investigator 3498
🇸🇪Skoevde, Sweden
Site Ref # / Investigator 3489
🇸🇪Stockholm, Sweden
Site Ref # / Investigator 3594
🇸🇪Umea, Sweden
Site Ref # / Investigator 3323
🇨🇭Basel, Switzerland
Site Ref # / Investigator 3322
🇨🇭Lausanne, Switzerland
Site Ref # / Investigator 4590
🇬🇧Cardiff, United Kingdom
Site Ref # / Investigator 3321
🇨🇭Bern, Switzerland
Site Ref # / Investigator 4604
🇬🇧Barnstaple, United Kingdom
Site Ref # / Investigator 3794
🇨🇭Zurich, Switzerland
Site Ref # / Investigator 4603
🇬🇧Dundee, United Kingdom
Site Ref # / Investigator 4588
🇬🇧Harrow, United Kingdom
Site Ref # / Investigator 4596
🇬🇧London, United Kingdom
Site Ref # / Investigator 4579
🇬🇧Edinburgh, United Kingdom
Site Ref # / Investigator 4595
🇬🇧London, United Kingdom
Site Ref # / Investigator 4607
🇬🇧London, United Kingdom
Site Ref # / Investigator 4586
🇬🇧Liverpool, United Kingdom
Site Ref # / Investigator 4580
🇬🇧London, United Kingdom
Site Ref # / Investigator 4589
🇬🇧Plymouth, United Kingdom
Site Ref # / Investigator 4591
🇬🇧Nottingham, United Kingdom
Site Ref # / Investigator 4578
🇬🇧Southampton, United Kingdom
Site Ref # / Investigator 4592
🇬🇧Portsmouth, United Kingdom
Site Ref # / Investigator 4598
🇬🇧Stockport, United Kingdom
Site Ref # / Investigator 4597
🇬🇧Rotherham, United Kingdom
Site Ref # / Investigator 4584
🇬🇧Sheffield, United Kingdom
Site Ref # / Investigator 2999
🇪🇸Madrid, Spain
Site Ref # / Investigator 3447
🇪🇸Madrid, Spain
Site Ref # / Investigator 3023
🇧🇪Bonheiden, Belgium
Site Ref # / Investigator 3618
🇳🇴Bergen, Norway
Site Ref # / Investigator 3020
🇧🇪Edegem, Belgium
Site Ref # / Investigator 3494
🇸🇰Presov, Slovakia
Site Ref # / Investigator 3074
🇧🇪Brussels, Belgium
Site Ref # / Investigator 3773
🇧🇪Leuven, Belgium
Site Ref # / Investigator 4972
🇵🇹Lisbon, Portugal
Site Ref # / Investigator 3068
🇵🇹Lisbon, Portugal
Site Ref # / Investigator 3619
🇳🇴Oslo, Norway