Long-term Open-label Safety and Efficacy Study of Adalimumab in Subjects With Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
To assess the long-term safety and maintenance of response of adalimumab in subjects with ulcerative colitis who participated in and successfully completed M06-826 (NCT00385736) or M06-827 (NCT00408629).

Official Title
-----------------
A Multicenter, Open-Label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab to Evaluate the Long Term Safety and Tolerability of Repeated Administration of Adalimumab in Subjects With Ulcerative Colitis

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Biological: adalimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have successfully enrolled and completed either study M06-826 (NCT00385736) or study M06-827 (NCT00408629) Subject is judged to be in generally good health as determined by the principal investigator Exclusion Criteria: Subject has not responded to weekly adalimumab therapy in M06-826 (NCT00385736) or M06-827 (NCT00408629) Subject considered by the investigator, for any reason, to be an unsuitable candidate Female subject who is pregnant or breast-feeding or considering becoming pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab 40 mg EOW/EW<br>Open-label adalimumab 40 mg every other week (EOW) or every week (EW). Participants who entered from an open-label cohort continued their previous dosing regimen of adalimumab EOW or EW; participants who entered from a double-blind cohort received adalimumab EOW. | Biological: adalimumab<br>* adalimumab prefilled syringes administered as subcutaneous injection EW or EOW<br>* Other names: HUMIRA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Mayo Score: Change From Baseline Over Time | The Partial Mayo score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Partial Mayo score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Mayo Score: Change From Baseline Over Time | The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Remission Per Partial Mayo Score Over Time | The Partial Mayo score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). Remission was defined as Partial Mayo score ≤ 2 with no subscore > 1. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Mayo Endoscopy Subscore: Change From Baseline Over Time | The Mayo Endoscopy subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo Endoscopy subscore indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Mayo Rectal Bleeding Subscore: Change From Baseline Over Time | The Mayo Rectal Bleeding subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo Rectal Bleeding subscore indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Mayo Physician's Global Assessment of Disease Severity Subscore: Change From Baseline Over Time | The Mayo Physician's Global Assessment of Disease Severity subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo Physician's Global Assessment of Disease Severity subscore indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Mayo Stool Frequency Subscore: Change From Baseline Over Time | The Mayo Stool Frequency subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo Stool Frequency subscore indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Inflammatory Bowel Disease Questionnaire (IBDQ): Change From Baseline Over Time | The IBDQ is a 32-item questionnaire that assesses how the subject felt during the 2 weeks before the measurement time point. Questions are related to symptoms the subject might have had as a result of UC, how the subject felt in general, how the subject's mood was, and social and work problems the subject might have that resulted from UC. An increase in IBDQ score indicates less impact of UC on the subject's life. The responses to each question range from 1 (significant impairment) to 7 (no impairment), with the total score ranging from 32 (very poor) to 224 (perfect health-related quality of life). | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| 36-Item Short Form Health Survey Version 2 (SF-36) Mental Component Score: Change From Baseline Over Time | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical [PCS]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 (poorest health) to 100 (best health) scale with higher scores indicating better health status or functioning. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| 36-Item Short Form Health Survey Version 2 (SF-36) Physical Component Score: Change From Baseline Over Time | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical [PCS]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 (poorest health) to 100 (best health) scale with higher scores indicating better health status or functioning. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Work Productivity and Activity Impairment: General Health Version 2.0 (WPAI:GH) Work Time Missed Because of Ulcerative Colitis: Change From Baseline Over Time | The WPAI:GH questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis in the last 7 days. The self-administered questionnaire measures the effect of the subject's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| WPAI:GH Impairment While Working: Change From Baseline Over Time | The WPAI:GH questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis in the last 7 days. The self-administered questionnaire measures the effect of the subject's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| WPAI:GH Overall Work Impairment: Change From Baseline Over Time | The WPAI:GH questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis in the last 7 days. The self-administered questionnaire measures the effect of the subject's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| WPAI:GH Activity Impairment: Change From Baseline Over Time | The WPAI:GH questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis in the last 7 days. The self-administered questionnaire measures the effect of the subject's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. | Baseline (Week 0), Weeks 48, 96, 144, 192, 240, 292, 340, 388 | 
| Colectomy Rate | The colectomy rates were estimated using Kaplan-Meier methodology based on the time to first colectomy. | 5 years | 
| Health Care Resource Utilization (HCRU): Cumulative Number of Unscheduled Utilizations | The HCRU assesses the frequency of unscheduled outpatient visits, emergency room visits, or hospitalizations due to ulcerative colitis since the last visit. The cumulative number of unscheduled utilizations over the course of the study is presented. | 5 years | 
| Number of Participants With Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section. | From first dose of study drug until 70 days after the last dose of study drug (up to 398 weeks) | 
| Hematology: Mean Change From Baseline to Final Values in Hemoglobin | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Hematology: Mean Change From Baseline to Final Values in Hematocrit | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Hematology: Mean Change From Baseline to Final Values in Red Blood Cell Count, Platelet Count, White Blood Cell Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Clinical Chemistry: Mean Change From Baseline to Final Values in Alanine Aminotransferase, Aspartate Aminotransferase, and Alkaline Phosphatase | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Clinical Chemistry: Mean Change From Baseline to Final Values in Total Bilirubin, Creatinine, and Uric Acid | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Clinical Chemistry: Mean Change From Baseline to Final Values in Blood Urea Nitrogen, Inorganic Phosphate, Calcium, Sodium, Potassium, Glucose, Cholesterol, and Triglycerides | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Clinical Chemistry: Mean Change From Baseline to Final Values in Albumin and Total Protein | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 
| Clinical Chemistry: Mean Change From Baseline to Final Values in High-sensitivity C-reactive Protein | Blood samples for laboratory tests were performed at each study visit after questionnaires and vital sign determinations. | Baseline (Week 0), final value (up to 5 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ulcerative Colitis