Human Anti-TNF Monoclonal Antibody Adalimumab in Canadian Subjects With Moderate to Severe Crohn's Disease (ACCESS)

Study Overview
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Brief Summary
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To make adalimumab available to subjects suffering from moderately to severely active Crohn's Disease (CD) and to expand the safety information on adalimumab. The study also assessed changes in Patient Reported Outcome Measures from baseline.

Detailed Description
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This was a Phase 3, multicenter, open-label, Early Access Study with an induction regimen of adalimumab 160 mg subcutaneous (SC) at Baseline and 80 mg SC at Week 2, followed by maintenance dosing of 40 mg every other week (eow) starting at Week 4 in subjects with moderately to severely active Crohn's Disease (CD) who were eligible to receive biologic therapy or who had failed to respond to, lost response to, or were intolerant to infliximab. Failure of prior therapy was determined by the Investigator. Subjects were to have an 8-week wash-out period prior to Baseline from the last dose of infliximab.

Official Title
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A Multicentre, Open Label, Treatment Protocol of the Human Anti-TNF Monoclonal Antibody Adalimumab in Canadian Subjects With Moderate to Severe Crohn's Disease (ACCESS)

Conditions
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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: Males or females 18 years of age and older Females: Not of childbearing potential OR Practicing approved birth control throughout the study and for 150 days after study completion Diagnosis of moderate to severe CD for greater than 16 weeks prior to screening; Crohn's Disease Activity Index score > 220 OR Harvey Bradshaw Index equal to or higher than 7, and who are refractory to optimal conventional therapies such as, 5-aminosalicylic acid (5-ASA), glucocorticoids, and immunosuppressive therapies (azathioprine, 6-MP and MTX) Subjects who failed prior infliximab therapy (as determined by the primary investigator), including those who never clinically responded (primary non-responders) Exclusion Criteria: History of cancer other than some skin and cervical cancers History of opportunistic infections, central nervous system (CNS) demyelinating disease, chronic viral hepatitis, or untreated tuberculosis Subjects with other, poorly controlled medical conditions Subjects with any prior exposure to Tysabri® (natalizumab) Subjects who have received any investigational agent in the past 30 days or 5 half-lives prior to screening (whichever is longer) Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Open Label | Biological: adalimumab<br>* 160 mg loading dose, 80 mg at week 2, 40 mg every other week<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Extent of Exposure - Duration in Days | Extent of exposure for all adalimumab treated subjects | Up to 24 weeks | 
| Total Number of Injections of Adalimumab | Extent of exposure for all adalimumab treated subjects | Up to 24 weeks | 
| Compliance With Number of Injections of Adalimumab. Compliance Corresponds to Patients Who Received Their Injections. | Treatment compliance (%) = 100 * (Number of doses of study medication actually received)/(Number of doses planned during the subject's participation in the study). | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fistula Count Mean Change From Baseline (Change in Number of Fistulas From Baseline). | Draining fistula counts is the sum of abdominal and perianal fistulas for each subject at each visit. | Week 12, Week 24, and Last Assessment Value (last nonmissing value) | 
| Overall Health Care Resource Utilization | From the Overall Health Care Resource Utilization Questionnaire: Number visits to physician, number visits to Emergency Room, number of hospital admissions, number of days of hospitalization. | Up to 24 weeks | 
| Employment Status: Number of Subjects Employed | Summary of employment status of those employed. | Baseline, Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | 
| 50% Improvement in Draining Fistula Count and Fistula Healing | Decrease in draining fistula is beneficial. 50 percent improvement refers to a reduction in the number of baseline fistula by 50 percent. | Week 12, Week 24, Last Assessment Value (last nonmissing value) | 
| Work Productivity and Activity Impairment - Change From Baseline in Overall Work Impairment | Scores are expressed as impairment percentages, higher numbers indicate greater impairment and less productivity (0% = no impairment; 100% = total loss of work productivity). Minimal clinically important difference = 7 points. Measure is Mean percent change. | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | 
| Hematology - Change From Baseline to Final Visit | Changes from the Group mean at baseline are compared to the final visit Group mean value | Up to 24 weeks | 
| Clinical Chemistry - Change From Baseline to Final Visit | Changes from the Group mean at Baseline are compared to the final visit Group mean value | Up to 24 weeks | 
| Urinalysis - Change From Baseline to Final Visit | Changes from the Group mean at baseline are compared to the final visit Group mean value | Up to 24 weeks | 
| Work Productivity and Activity Impairment - Change From Baseline in Absenteeism | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. | Weeks 4, 8, 12, and 24, and Last Assessmentl Value (last nonmissing value) | 
| Work Productivity and Activity Impairment - Change From Baseline in Presenteeism | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) | 
| Work Productivity and Activity Impairment - Change From Baseline in Activity Impairment | The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool used to assess the impact of disease on productivity. There are four component scores for WPAI: absenteeism, presenteeism, total work productivity impairment, daily activity impairment. The score for each component ranges from 0% to 100% (0%=no impairment; 100%=total loss of work productivity or activity). The minimal clinically important difference (MCID) is an absolute change of 7%. | Weeks 4, 8, 12, and 24, and Last Assessment Value (last nonmissing value) |