Study of Adalimumab Treatment for Induction and Maintenance of Clinical Remission in Subjects With Crohn's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00409617
First received: December 8, 2006
Last updated: October 6, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Biological: adalimumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label Study of the Fully Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderate to Severe Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5. [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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:
  • 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. [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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. [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 20 of treatment ] [ Designated as safety issue: No ]
    Daily activity is one component of the Work Productivity and Activity Impairment Questionnaire. 0% = no impairment. A decrease in the mean indicates improvement.


Enrollment: 945
Study Start Date: December 2006
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label Biological: adalimumab
Adalimumab 40 mg Every Other Week dosing
Other Names:
  • adalimumab
  • Humira
Biological: adalimumab
Adalimumab 40 mg Every Week dosing if participant experiences a disease flare or is not responding to treatment. A disease flare is defined as an increase of 3 points or more on the HBI compared to the Baseline score and a total HBI score of 7 or higher. Non-response is defined as a decrease by fewer than 3 points in the HBI compared to Baseline.
Other Names:
  • adalimumab
  • Humira

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00409617

  Hide Study Locations
Locations
Austria
Site Ref # / Investigator 3077
Graz, Austria, 8036
Site Ref # / Investigator 2975
Vienna, Austria, 1060
Site Ref # / Investigator 2976
Vienna, Austria, 1090
Site Ref # / Investigator 2978
Vienna, Austria, 1030
Site Ref # / Investigator 2977
Wels, Austria, A-4600
Belgium
Site Ref # / Investigator 3023
Bonheiden, Belgium, 2820
Site Ref # / Investigator 3021
Brussels, Belgium, 1090
Site Ref # / Investigator 3074
Brussels, Belgium, 1200
Site Ref # / Investigator 3020
Edegem, Belgium, 2650
Site Ref # / Investigator 3625
Ghent, Belgium, 9000
Site Ref # / Investigator 3773
Leuven, Belgium, 3000
Site Ref # / Investigator 3022
Liege, Belgium, 4000
Site Ref # / Investigator 3047
Roeselare, Belgium, 8800
Czech Republic
Site Ref # / Investigator 3893
Brno, Czech Republic, 62500
Site Ref # / Investigator 4657
Olomouc, Czech Republic, 77520
Site Ref # / Investigator 4660
Prague 5, Czech Republic, 15006
Site Ref # / Investigator 4659
Prague 7, Czech Republic, 17000
Denmark
Site Ref # / Investigator 3075
Aalborg, Denmark, 9000
Site Ref # / Investigator 3037
Aarhus C, Denmark, 8000
Site Ref # / Investigator 3088
Helsingor, Denmark, 3000
Site Ref # / Investigator 3076
Hvidovre, Denmark, 2650
Site Ref # / Investigator 3019
Odense C, Denmark, 5000
Finland
Site Ref # / Investigator 3623
Hyvinkaa, Finland, 05850
France
Site Ref # / Investigator 3032
Amiens, France, 80054
Site Ref # / Investigator 3012
Besancon, France, 25000
Site Ref # / Investigator 2983
Bethune, France, 62408
Site Ref # / Investigator 2993
Bordeaux, France, 33075
Site Ref # / Investigator 2982
Caen, France, 14033
Site Ref # / Investigator 3015
Clichy, France, 92110
Site Ref # / Investigator 3011
Colombes, France, 92701
Site Ref # / Investigator 3030
Creteil, France, 94010
Site Ref # / Investigator 3033
Creteil, France, 94010
Site Ref # / Investigator 3027
Evry, France, 91014
Site Ref # / Investigator 3048
Grenoble, France, 38043
Site Ref # / Investigator 3097
Lille Cedex, France, 59037
Site Ref # / Investigator 3031
Marseilles, France, 13015
Site Ref # / Investigator 2985
Montfermeil, France, 93370
Site Ref # / Investigator 2994
Montpellier, France, 34000
Site Ref # / Investigator 3014
Nantes, France, 44035
Site Ref # / Investigator 3029
Nice, France, 06202
Site Ref # / Investigator 3016
Paris, France, 75679
Site Ref # / Investigator 2996
Paris, France, 75571
Site Ref # / Investigator 2995
Paris, France, 75018
Site Ref # / Investigator 3017
Paris, France, 75014
Site Ref # / Investigator 4275
Paris, France, 75908
Site Ref # / Investigator 3025
Paris Cedex 10, France, 75475
Site Ref # / Investigator 3026
Pessac Cedex, France, 33600
Site Ref # / Investigator 2974
Pierre Benite, France, 69495
Site Ref # / Investigator 3013
Reims, France, 51092
Site Ref # / Investigator 3024
Rouen, France, 76031
Site Ref # / Investigator 2973
Strasbourg, France, 67089
Site Ref # / Investigator 2986
Toulouse, France, 31059
Site Ref # / Investigator 3018
Vandoeuvre Les Nancy, France, 54511
Germany
Site Ref # / Investigator 2969
Augsburg, Germany, D-86156
Site Ref # / Investigator 3070
Berlin, Germany, 12200
Site Ref # / Investigator 3041
Berlin, Germany, 10367
Site Ref # / Investigator 2980
Berlin, Germany, 13353
Site Ref # / Investigator 3096
Berlin, Germany, 10117
Site Ref # / Investigator 3089
Berlin, Germany, 14089
Site Ref # / Investigator 3084
Bochum, Germany, 44791
Site Ref # / Investigator 3051
Bochum, Germany, D-44789
Site Ref # / Investigator 3086
Braunschweig, Germany, 38126
Site Ref # / Investigator 3094
Cottbus, Germany, D-03048
Site Ref # / Investigator 2972
Dachau, Germany, 85221
Site Ref # / Investigator 3053
Dresden, Germany, 01067
Site Ref # / Investigator 3368
Dueren, Germany, 52351
Site Ref # / Investigator 3052
Erlangen, Germany, D-91054
Site Ref # / Investigator 3085
Essen, Germany, D-45239
Site Ref # / Investigator 3092
Frankfurt, Germany, 60318
Site Ref # / Investigator 3040
Freiburg, Germany, D-79106
Site Ref # / Investigator 3066
Halle, Germany, 06120
Site Ref # / Investigator 2981
Hamburg, Germany, 20148
Site Ref # / Investigator 3044
Hamburg, Germany, 20148
Site Ref # / Investigator 3082
Hamburg, Germany, 22559
Site Ref # / Investigator 3043
Hamburg, Germany, 22297
Site Ref # / Investigator 2979
Hamburg, Germany, 20246
Site Ref # / Investigator 3081
Hannover, Germany, 30625
Site Ref # / Investigator 3072
Heidelberg, Germany, 69120
Site Ref # / Investigator 3093
Herne, Germany, 44623
Site Ref # / Investigator 3080
Jena, Germany, 07747
Site Ref # / Investigator 3034
Karlsruhe, Germany, 76133
Site Ref # / Investigator 3617
Kiel, Germany, 24105
Site Ref # / Investigator 3071
Leipzig, Germany, 04103
Site Ref # / Investigator 3091
Luebeck, Germany, 23538
Site Ref # / Investigator 3090
Magdeburg, Germany, 39120
Site Ref # / Investigator 3083
Mainz, Germany, 55131
Site Ref # / Investigator 3049
Mainz, Germany, 55116
Site Ref # / Investigator 3073
Mannheim, Germany, 68161
Site Ref # / Investigator 3050
Minden, Germany, 32423
Site Ref # / Investigator 3056
Muenster, Germany, 48129
Site Ref # / Investigator 3057
Muenster, Germany, 48159
Site Ref # / Investigator 3054
Munich, Germany, 81925
Site Ref # / Investigator 3055
Munich, Germany, 81377
Site Ref # / Investigator 3098
Munich, Germany, 80639
Site Ref # / Investigator 3046
Osnabrueck, Germany, 49076
Site Ref # / Investigator 3078
Regensburg, Germany, 93053
Site Ref # / Investigator 3095
Rostock, Germany, 18057
Site Ref # / Investigator 2970
Rottenburg, Germany, 72108
Site Ref # / Investigator 3042
Stade, Germany, 21682
Site Ref # / Investigator 3079
Stuttgart, Germany, D-70376
Site Ref # / Investigator 3045
Stuttgart, Germany, 70565
Greece
Site Ref # / Investigator 4358
Athens, Greece, 124 62
Site Ref # / Investigator 4352
Athens, Greece, 106 76
Site Ref # / Investigator 4357
Athens, Greece, 106-76
Site Ref # / Investigator 4606
Heraklion, Greece, 71100
Site Ref # / Investigator 4355
Ioannina, Greece, 45500
Site Ref # / Investigator 4353
Nikaia, Greece, 184 54
Site Ref # / Investigator 4359
Thessaloniki, Greece, 54642
Site Ref # / Investigator 4351
Thessaloniki, Greece, 57010
Ireland
Site Ref # / Investigator 3326
Cork, Ireland
Site Ref # / Investigator 3325
Dublin 24, Ireland
Site Ref # / Investigator 3324
Dublin 9, Ireland
Italy
Site Ref # / Investigator 3953
Bologna, Italy, 40138
Site Ref # / Investigator 3061
Florence, Italy, 50134
Site Ref # / Investigator 3035
Milan, Italy, 20157
Site Ref # / Investigator 3065
Naples, Italy, 80131
Site Ref # / Investigator 3036
Padova, Italy, 35128
Site Ref # / Investigator 3062
Palermo, Italy, 90146
Site Ref # / Investigator 3063
Pavia, Italy, 27100
Site Ref # / Investigator 3058
Pescara, Italy, 65100
Site Ref # / Investigator 3039
Rome, Italy, 00186
Site Ref # / Investigator 3064
Rome, Italy, 00133
Site Ref # / Investigator 2991
Rome, Italy, 00152
Site Ref # / Investigator 3087
Rozzano, Italy, 20089
Site Ref # / Investigator 3038
San Donato Milanese, Italy, 20097
Norway
Site Ref # / Investigator 3618
Bergen, Norway, 5021
Site Ref # / Investigator 3629
Bodo, Norway, N-8092
Site Ref # / Investigator 3630
Hamar, Norway, N-2326
Site Ref # / Investigator 3620
Oslo, Norway, 0370
Site Ref # / Investigator 3619
Oslo, Norway, 0514
Portugal
Site Ref # / Investigator 3596
Braga, Portugal, 4700-308
Site Ref # / Investigator 3069
Coimbra, Portugal, 3000-075
Site Ref # / Investigator 3068
Lisbon, Portugal, 1649-035
Site Ref # / Investigator 4972
Lisbon, Portugal, 1150-069
Slovakia
Site Ref # / Investigator 3493
Bratislava, Slovakia, SK-813 69
Site Ref # / Investigator 4626
Kosice, Slovakia, 04001
Site Ref # / Investigator 3494
Presov, Slovakia, 08001
Spain
Site Ref # / Investigator 3448
Alicante, Spain, 03010
Site Ref # / Investigator 3009
Badalona - Barcelona, Spain, 08916
Site Ref # / Investigator 3005
Barakaldo, Spain, 48903
Site Ref # / Investigator 2989
Barcelona, Spain, 08035
Site Ref # / Investigator 3486
Barcelona, Spain, 08097
Site Ref # / Investigator 3002
Barcelona, Spain, 08036
Site Ref # / Investigator 2990
Barcelona, Spain, 08003
Site Ref # / Investigator 2998
Cabuenes-Gijon, Spain, 33203
Site Ref # / Investigator 2988
Galdakano, Spain, 48960
Site Ref # / Investigator 4383
Las Palmas de Gran Canaria, Spain, 35020
Site Ref # / Investigator 3484
Madrid, Spain, 28035
Site Ref # / Investigator 3595
Madrid, Spain, 28299
Site Ref # / Investigator 2999
Madrid, Spain, 28041
Site Ref # / Investigator 2997
Madrid, Spain, 28040
Site Ref # / Investigator 3447
Madrid, Spain, 28046
Site Ref # / Investigator 3008
Palma de Mallorca, Spain, 07014
Site Ref # / Investigator 3000
Santander, Spain, 39008
Site Ref # / Investigator 3003
Valencia, Spain, 46010
Site Ref # / Investigator 3007
Zaragoza, Spain, 50009
Site Ref # / Investigator 3010
Zaragoza, Spain, 50009
Sweden
Site Ref # / Investigator 3500
Gothenburg, Sweden, 416 85
Site Ref # / Investigator 3895
Gothenburg, Sweden, 41345
Site Ref # / Investigator 3499
Linkoping, Sweden, 581 85
Site Ref # / Investigator 3488
Lund, Sweden, 22185
Site Ref # / Investigator 3892
Oestersund, Sweden, 83183
Site Ref # / Investigator 3498
Skoevde, Sweden, 541 85
Site Ref # / Investigator 3896
Stockholm, Sweden, 11883
Site Ref # / Investigator 3489
Stockholm, Sweden, 114 86
Site Ref # / Investigator 3487
Stockholm, Sweden, 171 76
Site Ref # / Investigator 3594
Umea, Sweden, 901 85
Switzerland
Site Ref # / Investigator 3323
Basel, Switzerland, 4031
Site Ref # / Investigator 3321
Bern, Switzerland, 3010
Site Ref # / Investigator 3322
Lausanne, Switzerland, 1011
Site Ref # / Investigator 3794
Zurich, Switzerland, 8091
United Kingdom
Site Ref # / Investigator 4604
Barnstaple, United Kingdom, EX31 4JB
Site Ref # / Investigator 4590
Cardiff, United Kingdom, CF14 4XW
Site Ref # / Investigator 4603
Dundee, United Kingdom, DD1 9SY
Site Ref # / Investigator 4579
Edinburgh, United Kingdom, EH4 2XU
Site Ref # / Investigator 4588
Harrow, United Kingdom, HA1 3UJ
Site Ref # / Investigator 4586
Liverpool, United Kingdom, L7 8XP
Site Ref # / Investigator 4607
London, United Kingdom, SE1 7EH
Site Ref # / Investigator 4580
London, United Kingdom, W12 ONN
Site Ref # / Investigator 4595
London, United Kingdom, NW1 2BU
Site Ref # / Investigator 4596
London, United Kingdom, SE5 9RS
Site Ref # / Investigator 4591
Nottingham, United Kingdom, NG7 2UH
Site Ref # / Investigator 4589
Plymouth, United Kingdom, PL6 8DH
Site Ref # / Investigator 4592
Portsmouth, United Kingdom, PO6 3LY
Site Ref # / Investigator 4597
Rotherham, United Kingdom, S60 2UD
Site Ref # / Investigator 4584
Sheffield, United Kingdom, S10 2JF
Site Ref # / Investigator 4578
Southampton, United Kingdom, SO16 6YD
Site Ref # / Investigator 4598
Stockport, United Kingdom, SK2 7JE
Site Ref # / Investigator 4581
Surrey, United Kingdom, CR7 7YE
Sponsors and Collaborators
Abbott
Investigators
Study Director: Paul Pollack, MD Abbott
  More Information

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00409617     History of Changes
Other Study ID Numbers: M06-829, EudraCT:2006-002078-23
Study First Received: December 8, 2006
Results First Received: July 24, 2009
Last Updated: October 6, 2011
Health Authority: Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Antibodies, Monoclonal
Adalimumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 15, 2014