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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00409617
• Other study ID #: M06-829
• Secondary ID: EudraCT:2006-002
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2006
• Last updated: October 6, 2011
• Start date: December 2006
• Est. completion date: July 2008

Study information

• Verified date: October 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 945
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• adalimumab
Adalimumab 40 mg Every Other Week dosing
• 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.

Locations

Country	Name	City	State
Austria	Site Ref # / Investigator 3077	Graz
Austria	Site Ref # / Investigator 2975	Vienna
Austria	Site Ref # / Investigator 2976	Vienna
Austria	Site Ref # / Investigator 2978	Vienna
Austria	Site Ref # / Investigator 2977	Wels
Belgium	Site Ref # / Investigator 3023	Bonheiden
Belgium	Site Ref # / Investigator 3021	Brussels
Belgium	Site Ref # / Investigator 3074	Brussels
Belgium	Site Ref # / Investigator 3020	Edegem
Belgium	Site Ref # / Investigator 3625	Ghent
Belgium	Site Ref # / Investigator 3773	Leuven
Belgium	Site Ref # / Investigator 3022	Liege
Belgium	Site Ref # / Investigator 3047	Roeselare
Czech Republic	Site Ref # / Investigator 3893	Brno
Czech Republic	Site Ref # / Investigator 4657	Olomouc
Czech Republic	Site Ref # / Investigator 4660	Prague 5
Czech Republic	Site Ref # / Investigator 4659	Prague 7
Denmark	Site Ref # / Investigator 3075	Aalborg
Denmark	Site Ref # / Investigator 3037	Aarhus C
Denmark	Site Ref # / Investigator 3088	Helsingor
Denmark	Site Ref # / Investigator 3076	Hvidovre
Denmark	Site Ref # / Investigator 3019	Odense C
Finland	Site Ref # / Investigator 3623	Hyvinkaa
France	Site Ref # / Investigator 3032	Amiens
France	Site Ref # / Investigator 3012	Besancon
France	Site Ref # / Investigator 2983	Bethune
France	Site Ref # / Investigator 2993	Bordeaux
France	Site Ref # / Investigator 2982	Caen
France	Site Ref # / Investigator 3015	Clichy
France	Site Ref # / Investigator 3011	Colombes
France	Site Ref # / Investigator 3030	Creteil
France	Site Ref # / Investigator 3033	Creteil
France	Site Ref # / Investigator 3027	Evry
France	Site Ref # / Investigator 3048	Grenoble
France	Site Ref # / Investigator 3097	Lille Cedex
France	Site Ref # / Investigator 3031	Marseilles
France	Site Ref # / Investigator 2985	Montfermeil
France	Site Ref # / Investigator 2994	Montpellier
France	Site Ref # / Investigator 3014	Nantes
France	Site Ref # / Investigator 3029	Nice
France	Site Ref # / Investigator 2995	Paris
France	Site Ref # / Investigator 2996	Paris
France	Site Ref # / Investigator 3016	Paris
France	Site Ref # / Investigator 3017	Paris
France	Site Ref # / Investigator 4275	Paris
France	Site Ref # / Investigator 3025	Paris Cedex 10
France	Site Ref # / Investigator 3026	Pessac Cedex
France	Site Ref # / Investigator 2974	Pierre Benite
France	Site Ref # / Investigator 3013	Reims
France	Site Ref # / Investigator 3024	Rouen
France	Site Ref # / Investigator 2973	Strasbourg
France	Site Ref # / Investigator 2986	Toulouse
France	Site Ref # / Investigator 3018	Vandoeuvre Les Nancy
Germany	Site Ref # / Investigator 2969	Augsburg
Germany	Site Ref # / Investigator 2980	Berlin
Germany	Site Ref # / Investigator 3041	Berlin
Germany	Site Ref # / Investigator 3070	Berlin
Germany	Site Ref # / Investigator 3089	Berlin
Germany	Site Ref # / Investigator 3096	Berlin
Germany	Site Ref # / Investigator 3051	Bochum
Germany	Site Ref # / Investigator 3084	Bochum
Germany	Site Ref # / Investigator 3086	Braunschweig
Germany	Site Ref # / Investigator 3094	Cottbus
Germany	Site Ref # / Investigator 2972	Dachau
Germany	Site Ref # / Investigator 3053	Dresden
Germany	Site Ref # / Investigator 3368	Dueren
Germany	Site Ref # / Investigator 3052	Erlangen
Germany	Site Ref # / Investigator 3085	Essen
Germany	Site Ref # / Investigator 3092	Frankfurt
Germany	Site Ref # / Investigator 3040	Freiburg
Germany	Site Ref # / Investigator 3066	Halle
Germany	Site Ref # / Investigator 2979	Hamburg
Germany	Site Ref # / Investigator 2981	Hamburg
Germany	Site Ref # / Investigator 3043	Hamburg
Germany	Site Ref # / Investigator 3044	Hamburg
Germany	Site Ref # / Investigator 3082	Hamburg
Germany	Site Ref # / Investigator 3081	Hannover
Germany	Site Ref # / Investigator 3072	Heidelberg
Germany	Site Ref # / Investigator 3093	Herne
Germany	Site Ref # / Investigator 3080	Jena
Germany	Site Ref # / Investigator 3034	Karlsruhe
Germany	Site Ref # / Investigator 3617	Kiel
Germany	Site Ref # / Investigator 3071	Leipzig
Germany	Site Ref # / Investigator 3091	Luebeck
Germany	Site Ref # / Investigator 3090	Magdeburg
Germany	Site Ref # / Investigator 3049	Mainz
Germany	Site Ref # / Investigator 3083	Mainz
Germany	Site Ref # / Investigator 3073	Mannheim
Germany	Site Ref # / Investigator 3050	Minden
Germany	Site Ref # / Investigator 3056	Muenster
Germany	Site Ref # / Investigator 3057	Muenster
Germany	Site Ref # / Investigator 3054	Munich
Germany	Site Ref # / Investigator 3055	Munich
Germany	Site Ref # / Investigator 3098	Munich
Germany	Site Ref # / Investigator 3046	Osnabrueck
Germany	Site Ref # / Investigator 3078	Regensburg
Germany	Site Ref # / Investigator 3095	Rostock
Germany	Site Ref # / Investigator 2970	Rottenburg
Germany	Site Ref # / Investigator 3042	Stade
Germany	Site Ref # / Investigator 3045	Stuttgart
Germany	Site Ref # / Investigator 3079	Stuttgart
Greece	Site Ref # / Investigator 4352	Athens
Greece	Site Ref # / Investigator 4357	Athens
Greece	Site Ref # / Investigator 4358	Athens
Greece	Site Ref # / Investigator 4606	Heraklion
Greece	Site Ref # / Investigator 4355	Ioannina
Greece	Site Ref # / Investigator 4353	Nikaia
Greece	Site Ref # / Investigator 4351	Thessaloniki
Greece	Site Ref # / Investigator 4359	Thessaloniki
Ireland	Site Ref # / Investigator 3326	Cork
Ireland	Site Ref # / Investigator 3325	Dublin 24
Ireland	Site Ref # / Investigator 3324	Dublin 9
Italy	Site Ref # / Investigator 3953	Bologna
Italy	Site Ref # / Investigator 3061	Florence
Italy	Site Ref # / Investigator 3035	Milan
Italy	Site Ref # / Investigator 3065	Naples
Italy	Site Ref # / Investigator 3036	Padova
Italy	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 3039	Rome
Italy	Site Ref # / Investigator 3064	Rome
Italy	Site Ref # / Investigator 3087	Rozzano
Italy	Site Ref # / Investigator 3038	San Donato Milanese
Norway	Site Ref # / Investigator 3618	Bergen
Norway	Site Ref # / Investigator 3629	Bodo
Norway	Site Ref # / Investigator 3630	Hamar
Norway	Site Ref # / Investigator 3619	Oslo
Norway	Site Ref # / Investigator 3620	Oslo
Portugal	Site Ref # / Investigator 3596	Braga
Portugal	Site Ref # / Investigator 3069	Coimbra
Portugal	Site Ref # / Investigator 3068	Lisbon
Portugal	Site Ref # / Investigator 4972	Lisbon
Slovakia	Site Ref # / Investigator 3493	Bratislava
Slovakia	Site Ref # / Investigator 4626	Kosice
Slovakia	Site Ref # / Investigator 3494	Presov
Spain	Site Ref # / Investigator 3448	Alicante
Spain	Site Ref # / Investigator 3009	Badalona - Barcelona
Spain	Site Ref # / Investigator 3005	Barakaldo
Spain	Site Ref # / Investigator 2989	Barcelona
Spain	Site Ref # / Investigator 2990	Barcelona
Spain	Site Ref # / Investigator 3002	Barcelona
Spain	Site Ref # / Investigator 3486	Barcelona
Spain	Site Ref # / Investigator 2998	Cabuenes-Gijon
Spain	Site Ref # / Investigator 2988	Galdakano
Spain	Site Ref # / Investigator 4383	Las Palmas de Gran Canaria
Spain	Site Ref # / Investigator 2997	Madrid
Spain	Site Ref # / Investigator 2999	Madrid
Spain	Site Ref # / Investigator 3447	Madrid
Spain	Site Ref # / Investigator 3484	Madrid
Spain	Site Ref # / Investigator 3595	Madrid
Spain	Site Ref # / Investigator 3008	Palma de Mallorca
Spain	Site Ref # / Investigator 3000	Santander
Spain	Site Ref # / Investigator 3003	Valencia
Spain	Site Ref # / Investigator 3007	Zaragoza
Spain	Site Ref # / Investigator 3010	Zaragoza
Sweden	Site Ref # / Investigator 3500	Gothenburg
Sweden	Site Ref # / Investigator 3895	Gothenburg
Sweden	Site Ref # / Investigator 3499	Linkoping
Sweden	Site Ref # / Investigator 3488	Lund
Sweden	Site Ref # / Investigator 3892	Oestersund
Sweden	Site Ref # / Investigator 3498	Skoevde
Sweden	Site Ref # / Investigator 3487	Stockholm
Sweden	Site Ref # / Investigator 3489	Stockholm
Sweden	Site Ref # / Investigator 3896	Stockholm
Sweden	Site Ref # / Investigator 3594	Umea
Switzerland	Site Ref # / Investigator 3323	Basel
Switzerland	Site Ref # / Investigator 3321	Bern
Switzerland	Site Ref # / Investigator 3322	Lausanne
Switzerland	Site Ref # / Investigator 3794	Zurich
United Kingdom	Site Ref # / Investigator 4604	Barnstaple
United Kingdom	Site Ref # / Investigator 4590	Cardiff
United Kingdom	Site Ref # / Investigator 4603	Dundee
United Kingdom	Site Ref # / Investigator 4579	Edinburgh
United Kingdom	Site Ref # / Investigator 4588	Harrow
United Kingdom	Site Ref # / Investigator 4586	Liverpool
United Kingdom	Site Ref # / Investigator 4580	London
United Kingdom	Site Ref # / Investigator 4595	London
United Kingdom	Site Ref # / Investigator 4596	London
United Kingdom	Site Ref # / Investigator 4607	London
United Kingdom	Site Ref # / Investigator 4591	Nottingham
United Kingdom	Site Ref # / Investigator 4589	Plymouth
United Kingdom	Site Ref # / Investigator 4592	Portsmouth
United Kingdom	Site Ref # / Investigator 4597	Rotherham
United Kingdom	Site Ref # / Investigator 4584	Sheffield
United Kingdom	Site Ref # / Investigator 4578	Southampton
United Kingdom	Site Ref # / Investigator 4598	Stockport
United Kingdom	Site Ref # / Investigator 4581	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Ireland,  Italy,  Norway,  Portugal,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants in Clinical Remission at Treatment Week 20. Clinical Remission Defined as Harvey Bradshaw Index (HBI) Score Less Than 5.	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).	Week 20 of treatment	No
Secondary	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.	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).	Week 20 of treatment	No
Secondary	Number of Participants Who Had a Reduction in Number of Draining Fistulas of at Least 50% From Baseline to Week 20	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.	Week 20 of treatment	No
Secondary	Number of Participants Who Had Extra-intestinal Manifestations (EIM) at Baseline and Resolution by Week 20.	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.	Week 20 of treatment	No
Secondary	Mean Change in Total Score of Short Inflammatory Bowel Disease Questionnaire (SIBDQ) From Baseline to Week 20	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.	Week 20 of treatment	No
Secondary	Mean Change in Percent Work Time Missed Due to Crohn's Disease From Baseline to 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.	Week 20 of treatment	No
Secondary	Mean Change in Percent Impairment While Working From Baseline to 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.	Week 20 of treatment	No
Secondary	Mean Change in Overall Work Productivity and Activity Impairment Score From Baseline to Week 20	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).	Week 20 of treatment	No
Secondary	Mean Change in Activity Impairment Score From Baseline to Week 20	Daily activity is one component of the Work Productivity and Activity Impairment Questionnaire. 0% = no impairment. A decrease in the mean indicates improvement.	Week 20 of treatment	No