A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy, safety and pharmacokinetics after dose escalation in Japanese subjects with Crohn's Disease.

Detailed Description
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Subjects who are confirmed to meet all of the inclusion criteria and none of the exclusion criteria during screening period (≤ 21 days) will be given subcutaneous injections of open-label adalimumab 80 mg eow from Week 0 to Week 50. If a subject has an inadequate response at or after Week 8, the subject may be withdrawn from the study. Self-injection of study drug is permitted for the subjects who are willing to perform self-injection, if the investigator decided as appropriate. Disease activity will be evaluated by Crohn's disease activity index (CDAI) at Screening, Week 0 and every 4 weeks until Week 52. Follow-up will be performed at 70 days after the last dose of study drug by visit or telephone.

Official Title
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A Multicenter Open-label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab to Investigate Efficacy, Safety and Pharmacokinetics After Dose Escalation in Japanese Subjects With Crohn's Disease

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: Subject ≥ 15 years of age at the time of informed consent. Subject with Crohn's disease who received induction treatment of commercially available Humira® (160 mg initially and 80 mg at 2 weeks after initial dose), achieved response after initial dose, and then lost response during maintenance treatment with Humira®. Subject with elevated C-reactive Protein (CRP) at Screening. If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after the last dose of study drug. Subject has a negative tuberculosis (TB) screening assessment. If the subject has evidence of a latent TB infection; the subject must initiate and complete a minimum of 21 days of an ongoing TB prophylaxis (in such case, screening period can be prolonged until 21 days past after initiation of prophylaxis and study drug is administered) or have documented completion of a full course of TB prophylaxis, prior to Week 0. Exclusion Criteria: Subject with suspicion of colitis other than Crohn's disease. Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded). Subject with abscess or suspicion of abscess, or subject with infection(s).

Ages Eligible for Study
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Minimum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab 80 mg<br>All participants were to receive subcutaneous injections of open-label adalimumab 80 mg every other week from Week 0 to Week 50. | Biological: Adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection.<br>* Other names: Humira, ABT-D2E7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Clinical Response 50 (CR50; Crohn's Disease Activity Index [CDAI] Decrease ≥ 50 From Week 0) at Week 8 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Every 4 Weeks up to Week 52 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. | Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percentage of Participants Who Achieved Clinical Response 50 (CR50; Crohn's Disease Activity Index [CDAI] Decrease ≥ 50 From Week 0) Every 4 Weeks up to Week 52 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. Week 8 was the primary outcome measure. | Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percentage of Participants Who Achieved Clinical Response 70 (CR70; Crohn's Disease Activity Index [CDAI] Decrease ≥ 70 From Week 0) Every 4 Weeks up to Week 52 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. | Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percentage of Participants Who Achieved Clinical Response 100 (CR100; Crohn's Disease Activity Index [CDAI] Decrease of 100 From Week 0) Every 4 Weeks up to Week 52 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score above 450 indicates severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. | Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| C-reactive Protein (CRP): Mean Change From Baseline (Week 0) to Week 52 | C-reactive protein (CRP) was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Normal concentration in healthy human serum is usually lower than 0.3 mg/dL, slightly increasing with age. Last Observation Carried Forward (LOCF) was used for missing data. | Baseline (Week 0) and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Number of Participants With Potentially Significant Hematology Parameters | Blood was collected for analysis at designated study visits; hematology results were provided by each site laboratory. The number of participants with an abnormal laboratory result (higher than upper limit of normal [ULN] or lower than lower limit of normal [LLN]) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized. Increase is signified by ↑. n=the number of participants with CTC Grade <3 at baseline and a post-baseline value. | 52 weeks | 
| Number of Participants With Potentially Significant Clinical Chemistry Parameters | Blood was collected for analysis at designated study visits; chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher than upper limit of normal [ULN] or lower than lower limit of normal [LLN]) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized. n=the number of participants with CTC Grade <3 at baseline and a post-baseline value for each parameter. | 52 weeks | 
| Systolic Blood Pressure: Mean Change From Baseline (Week 0) to Each Visit | Blood pressure was measured while the participant was sitting. n=the number of participants with available data at each time point. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Diastolic Blood Pressure: Mean Change From Baseline (Week 0) to Each Visit | Blood pressure was measured while the participant was sitting. n=the number of participants with available data at each time point. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Heart Rate: Mean Change From Baseline (Week 0) to Each Visit | Heart rate was measured while the participant was sitting. n=the number of participants with available data at each time point. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Body Temperature: Mean Change From Baseline (Week 0) to Each Visit | n=the number of participants with available data at each time point. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (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 participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs or TESAE) are defined as any event that began or worsened in severity after the first dose of study drug. The investigator assessed the relationship of each event to the use of study drug as either Reasonable possibility or No reasonable possibility of being related to study drug. For more details on adverse events please see the AE section below. | 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose Escalation, Crohn's Disease