Clinical trial NCT00409617: Study of Adalimumab Treatment for Induction and Maintenance of Clinical Remission in Subjects With Crohn's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2006-12-11
Enrollment: 945
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5.
timeFrame: Week 20 of treatment
Secondary outcomes:
measure: 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.
timeFrame: Week 20 of treatment
measure: Number of Participants Who Had a Reduction in Number of Draining Fistulas of at Least 50% From Baseline to Week 20
timeFrame: Week 20 of treatment
measure: Number of Participants Who Had Extra-intestinal Manifestations (EIM) at Baseline and Resolution by Week 20.
timeFrame: Week 20 of treatment
measure: Mean Change in Total Score of Short Inflammatory Bowel Disease Questionnaire (SIBDQ) From Baseline to Week 20
timeFrame: Week 20 of treatment
measure: Mean Change in Percent Work Time Missed Due to Crohn's Disease From Baseline to Week 20 of Treatment
timeFrame: Week 20 of treatment
measure: Mean Change in Percent Impairment While Working From Baseline to Week 20 of Treatment
timeFrame: Week 20 of treatment
measure: Mean Change in Overall Work Productivity and Activity Impairment Score From Baseline to Week 20
timeFrame: Week 20 of treatment
measure: Mean Change in Activity Impairment Score From Baseline to Week 20
timeFrame: Week 20 of treatment
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Site Ref # / Investigator 3077
city: Vienna
country: Austria
facility: Site Ref # / Investigator 2978
city: Vienna
country: Austria
facility: Site Ref # / Investigator 2975
city: Vienna
country: Austria
facility: Site Ref # / Investigator 2976
city: Wels
country: Austria
facility: Site Ref # / Investigator 2977
city: Bonheiden
country: Belgium
facility: Site Ref # / Investigator 3023
city: Brussels
country: Belgium
facility: Site Ref # / Investigator 3021
city: Brussels
country: Belgium
facility: Site Ref # / Investigator 3074
city: Edegem
country: Belgium
facility: Site Ref # / Investigator 3020
city: Ghent
country: Belgium
facility: Site Ref # / Investigator 3625
city: Leuven
country: Belgium
facility: Site Ref # / Investigator 3773
city: Liege
country: Belgium
facility: Site Ref # / Investigator 3022
city: Roeselare
country: Belgium
facility: Site Ref # / Investigator 3047
city: Brno
country: Czech Republic
facility: Site Ref # / Investigator 3893
city: Olomouc
country: Czech Republic
facility: Site Ref # / Investigator 4657
city: Prague 5
country: Czech Republic
facility: Site Ref # / Investigator 4660
city: Prague 7
country: Czech Republic
facility: Site Ref # / Investigator 4659
city: Aalborg
country: Denmark
facility: Site Ref # / Investigator 3075
city: Aarhus C
country: Denmark
facility: Site Ref # / Investigator 3037
city: Helsingor
country: Denmark
facility: Site Ref # / Investigator 3088
city: Hvidovre
country: Denmark
facility: Site Ref # / Investigator 3076
city: Odense C
country: Denmark
facility: Site Ref # / Investigator 3019
city: Hyvinkaa
country: Finland
facility: Site Ref # / Investigator 3623
city: Amiens
country: France
facility: Site Ref # / Investigator 3032
city: Besancon
country: France
facility: Site Ref # / Investigator 3012
city: Bethune
country: France
facility: Site Ref # / Investigator 2983
city: Bordeaux
country: France
facility: Site Ref # / Investigator 2993
city: Caen
country: France
facility: Site Ref # / Investigator 2982
city: Clichy
country: France
facility: Site Ref # / Investigator 3015
city: Colombes
country: France
facility: Site Ref # / Investigator 3011
city: Creteil
country: France
facility: Site Ref # / Investigator 3030
city: Creteil
country: France
facility: Site Ref # / Investigator 3033
city: Evry
country: France
facility: Site Ref # / Investigator 3027
city: Grenoble
country: France
facility: Site Ref # / Investigator 3048
city: Lille Cedex
country: France
facility: Site Ref # / Investigator 3097
city: Marseilles
country: France
facility: Site Ref # / Investigator 3031
city: Montfermeil
country: France
facility: Site Ref # / Investigator 2985
city: Montpellier
country: France
facility: Site Ref # / Investigator 2994
city: Nantes
country: France
facility: Site Ref # / Investigator 3014
city: Nice
country: France
facility: Site Ref # / Investigator 3029
city: Paris Cedex 10
country: France
facility: Site Ref # / Investigator 3025
city: Paris
country: France
facility: Site Ref # / Investigator 3017
city: Paris
country: France
facility: Site Ref # / Investigator 2995
city: Paris
country: France
facility: Site Ref # / Investigator 2996
city: Paris
country: France
facility: Site Ref # / Investigator 3016
city: Paris
country: France
facility: Site Ref # / Investigator 4275
city: Pessac Cedex
country: France
facility: Site Ref # / Investigator 3026
city: Pierre Benite
country: France
facility: Site Ref # / Investigator 2974
city: Reims
country: France
facility: Site Ref # / Investigator 3013
city: Rouen
country: France
facility: Site Ref # / Investigator 3024
city: Strasbourg
country: France
facility: Site Ref # / Investigator 2973
city: Toulouse
country: France
facility: Site Ref # / Investigator 2986
city: Vandoeuvre Les Nancy
country: France
facility: Site Ref # / Investigator 3018
city: Augsburg
country: Germany
facility: Site Ref # / Investigator 2969
city: Berlin
country: Germany
facility: Site Ref # / Investigator 3096
city: Berlin
country: Germany
facility: Site Ref # / Investigator 3041
city: Berlin
country: Germany
facility: Site Ref # / Investigator 3070
city: Berlin
country: Germany
facility: Site Ref # / Investigator 2980
city: Berlin
country: Germany
facility: Site Ref # / Investigator 3089
city: Bochum
country: Germany
facility: Site Ref # / Investigator 3084
city: Bochum
country: Germany
facility: Site Ref # / Investigator 3051
city: Braunschweig
country: Germany
facility: Site Ref # / Investigator 3086
city: Cottbus
country: Germany
facility: Site Ref # / Investigator 3094
city: Dachau
country: Germany
facility: Site Ref # / Investigator 2972
city: Dresden
country: Germany
facility: Site Ref # / Investigator 3053
city: Dueren
country: Germany
facility: Site Ref # / Investigator 3368
city: Erlangen
country: Germany
facility: Site Ref # / Investigator 3052
city: Essen
country: Germany
facility: Site Ref # / Investigator 3085
city: Frankfurt
country: Germany
facility: Site Ref # / Investigator 3092
city: Freiburg
country: Germany
facility: Site Ref # / Investigator 3040
city: Halle
country: Germany
facility: Site Ref # / Investigator 3066
city: Hamburg
country: Germany
facility: Site Ref # / Investigator 2981
city: Hamburg
country: Germany
facility: Site Ref # / Investigator 3044
city: Hamburg
country: Germany
facility: Site Ref # / Investigator 2979
city: Hamburg
country: Germany
facility: Site Ref # / Investigator 3043
city: Hamburg
country: Germany
facility: Site Ref # / Investigator 3082
city: Hannover
country: Germany
facility: Site Ref # / Investigator 3081
city: Heidelberg
country: Germany
facility: Site Ref # / Investigator 3072
city: Herne
country: Germany
facility: Site Ref # / Investigator 3093
city: Jena
country: Germany
facility: Site Ref # / Investigator 3080
city: Karlsruhe
country: Germany
facility: Site Ref # / Investigator 3034
city: Kiel
country: Germany
facility: Site Ref # / Investigator 3617
city: Leipzig
country: Germany
facility: Site Ref # / Investigator 3071
city: Luebeck
country: Germany
facility: Site Ref # / Investigator 3091
city: Magdeburg
country: Germany
facility: Site Ref # / Investigator 3090
city: Mainz
country: Germany
facility: Site Ref # / Investigator 3049
city: Mainz
country: Germany
facility: Site Ref # / Investigator 3083
city: Mannheim
country: Germany
facility: Site Ref # / Investigator 3073
city: Minden
country: Germany
facility: Site Ref # / Investigator 3050
city: Muenster
country: Germany
facility: Site Ref # / Investigator 3056
city: Muenster
country: Germany
facility: Site Ref # / Investigator 3057
city: Munich
country: Germany
facility: Site Ref # / Investigator 3098
city: Munich
country: Germany
facility: Site Ref # / Investigator 3055
city: Munich
country: Germany
facility: Site Ref # / Investigator 3054
city: Osnabrueck
country: Germany
facility: Site Ref # / Investigator 3046
city: Regensburg
country: Germany
facility: Site Ref # / Investigator 3078
city: Rostock
country: Germany
facility: Site Ref # / Investigator 3095
city: Rottenburg
country: Germany
facility: Site Ref # / Investigator 2970
city: Stade
country: Germany
facility: Site Ref # / Investigator 3042
city: Stuttgart
country: Germany
facility: Site Ref # / Investigator 3045
city: Stuttgart
country: Germany
facility: Site Ref # / Investigator 3079
city: Athens
country: Greece
facility: Site Ref # / Investigator 4352
city: Athens
country: Greece
facility: Site Ref # / Investigator 4357
city: Athens
country: Greece
facility: Site Ref # / Investigator 4358
city: Heraklion
country: Greece
facility: Site Ref # / Investigator 4606
city: Ioannina
country: Greece
facility: Site Ref # / Investigator 4355
city: Nikaia
country: Greece
facility: Site Ref # / Investigator 4353
city: Thessaloniki
country: Greece
facility: Site Ref # / Investigator 4359
city: Thessaloniki
country: Greece
facility: Site Ref # / Investigator 4351
city: Cork
country: Ireland
facility: Site Ref # / Investigator 3326
city: Dublin 24
country: Ireland
facility: Site Ref # / Investigator 3325
city: Dublin 9
country: Ireland
facility: Site Ref # / Investigator 3324
city: Bologna
country: Italy
facility: Site Ref # / Investigator 3953
city: Florence
country: Italy
facility: Site Ref # / Investigator 3061
city: Milan
country: Italy
facility: Site Ref # / Investigator 3035
city: Naples
country: Italy
facility: Site Ref # / Investigator 3065
city: Padova
country: Italy
facility: Site Ref # / Investigator 3036
city: Palermo
country: Italy
facility: Site Ref # / Investigator 3062
city: Pavia
country: Italy
facility: Site Ref # / Investigator 3063
city: Pescara
country: Italy
facility: Site Ref # / Investigator 3058
city: Rome
country: Italy
facility: Site Ref # / Investigator 3064
city: Rome
country: Italy
facility: Site Ref # / Investigator 2991
city: Rome
country: Italy
facility: Site Ref # / Investigator 3039
city: Rozzano
country: Italy
facility: Site Ref # / Investigator 3087
city: San Donato Milanese
country: Italy
facility: Site Ref # / Investigator 3038
city: Bergen
country: Norway
facility: Site Ref # / Investigator 3618
city: Bodo
country: Norway
facility: Site Ref # / Investigator 3629
city: Hamar
country: Norway
facility: Site Ref # / Investigator 3630
city: Oslo
country: Norway
facility: Site Ref # / Investigator 3620
city: Oslo
country: Norway
facility: Site Ref # / Investigator 3619
city: Braga
country: Portugal
facility: Site Ref # / Investigator 3596
city: Coimbra
country: Portugal
facility: Site Ref # / Investigator 3069
city: Lisbon
country: Portugal
facility: Site Ref # / Investigator 4972
city: Lisbon
country: Portugal
facility: Site Ref # / Investigator 3068
city: Bratislava
country: Slovakia
facility: Site Ref # / Investigator 3493
city: Kosice
country: Slovakia
facility: Site Ref # / Investigator 4626
city: Presov
country: Slovakia
facility: Site Ref # / Investigator 3494
city: Alicante
country: Spain
facility: Site Ref # / Investigator 3448
city: Badalona - Barcelona
country: Spain
facility: Site Ref # / Investigator 3009
city: Barakaldo
country: Spain
facility: Site Ref # / Investigator 3005
city: Barcelona
country: Spain
facility: Site Ref # / Investigator 2990
city: Barcelona
country: Spain
facility: Site Ref # / Investigator 2989
city: Barcelona
country: Spain
facility: Site Ref # / Investigator 3002
city: Barcelona
country: Spain
facility: Site Ref # / Investigator 3486
city: Cabuenes-Gijon
country: Spain
facility: Site Ref # / Investigator 2998
city: Galdakano
country: Spain
facility: Site Ref # / Investigator 2988
city: Las Palmas de Gran Canaria
country: Spain
facility: Site Ref # / Investigator 4383
city: Madrid
country: Spain
facility: Site Ref # / Investigator 3484
city: Madrid
country: Spain
facility: Site Ref # / Investigator 2997
city: Madrid
country: Spain
facility: Site Ref # / Investigator 2999
city: Madrid
country: Spain
facility: Site Ref # / Investigator 3447
city: Madrid
country: Spain
facility: Site Ref # / Investigator 3595
city: Palma de Mallorca
country: Spain
facility: Site Ref # / Investigator 3008
city: Santander
country: Spain
facility: Site Ref # / Investigator 3000
city: Valencia
country: Spain
facility: Site Ref # / Investigator 3003
city: Zaragoza
country: Spain
facility: Site Ref # / Investigator 3007
city: Zaragoza
country: Spain
facility: Site Ref # / Investigator 3010
city: Gothenburg
country: Sweden
facility: Site Ref # / Investigator 3895
city: Gothenburg
country: Sweden
facility: Site Ref # / Investigator 3500
city: Linkoping
country: Sweden
facility: Site Ref # / Investigator 3499
city: Lund
country: Sweden
facility: Site Ref # / Investigator 3488
city: Oestersund
country: Sweden
facility: Site Ref # / Investigator 3892
city: Skoevde
country: Sweden
facility: Site Ref # / Investigator 3498
city: Stockholm
country: Sweden
facility: Site Ref # / Investigator 3489
city: Stockholm
country: Sweden
facility: Site Ref # / Investigator 3896
city: Stockholm
country: Sweden
facility: Site Ref # / Investigator 3487
city: Umea
country: Sweden
facility: Site Ref # / Investigator 3594
city: Basel
country: Switzerland
facility: Site Ref # / Investigator 3323
city: Bern
country: Switzerland
facility: Site Ref # / Investigator 3321
city: Lausanne
country: Switzerland
facility: Site Ref # / Investigator 3322
city: Zurich
country: Switzerland
facility: Site Ref # / Investigator 3794
city: Barnstaple
country: United Kingdom
facility: Site Ref # / Investigator 4604
city: Cardiff
country: United Kingdom
facility: Site Ref # / Investigator 4590
city: Dundee
country: United Kingdom
facility: Site Ref # / Investigator 4603
city: Edinburgh
country: United Kingdom
facility: Site Ref # / Investigator 4579
city: Harrow
country: United Kingdom
facility: Site Ref # / Investigator 4588
city: Liverpool
country: United Kingdom
facility: Site Ref # / Investigator 4586
city: London
country: United Kingdom
facility: Site Ref # / Investigator 4595
city: London
country: United Kingdom
facility: Site Ref # / Investigator 4607
city: London
country: United Kingdom
facility: Site Ref # / Investigator 4596
city: London
country: United Kingdom
facility: Site Ref # / Investigator 4580
city: Nottingham
country: United Kingdom
facility: Site Ref # / Investigator 4591
city: Plymouth
country: United Kingdom
facility: Site Ref # / Investigator 4589
city: Portsmouth
country: United Kingdom
facility: Site Ref # / Investigator 4592
city: Rotherham
country: United Kingdom
facility: Site Ref # / Investigator 4597
city: Sheffield
country: United Kingdom
facility: Site Ref # / Investigator 4584
city: Southampton
country: United Kingdom
facility: Site Ref # / Investigator 4578
city: Stockport
country: United Kingdom
facility: Site Ref # / Investigator 4598
city: Surrey
country: United Kingdom
facility: Site Ref # / Investigator 4581
Study officials:
affiliation: Abbott
name: Paul Pollack, MD
role: STUDY_DIRECTOR
References:
citation: Louis E, Lofberg R, Reinisch W, Camez A, Yang M, Pollack PF, Chen N, Chao J, Mulani PM. Adalimumab improves patient-reported outcomes and reduces indirect costs in patients with moderate to severe Crohn's disease: results from the CARE trial. J Crohns Colitis. 2013 Feb;7(1):34-43. doi: 10.1016/j.crohns.2012.02.017. Epub 2012 Apr 4.