Back to resultsA Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease
Primary Purpose
Crohn's Disease
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Adalimumab
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Dose Escalation, Crohn's Disease
Eligibility Criteria
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).
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Adalimumab 80 mg
Arm Description
All participants were to receive subcutaneous injections of open-label adalimumab 80 mg every other week from Week 0 to Week 50.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Body Temperature: Mean Change From Baseline (Week 0) to Each Visit
n=the number of participants with available data at each time point.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01958827
Brief Title
A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Dose Escalation, Crohn's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adalimumab 80 mg
Arm Type
Experimental
Arm Description
All participants were to receive subcutaneous injections of open-label adalimumab 80 mg every other week from Week 0 to Week 50.
Intervention Type
Biological
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira, ABT-D2E7
Intervention Description
Adalimumab pre-filled syringe, administered by subcutaneous injection.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Clinical Response 50 (CR50; Crohn's Disease Activity Index [CDAI] Decrease ≥ 50 From Week 0) at Week 8
Description
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.
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Clinical Remission (CDAI < 150) Every 4 Weeks up to Week 52
Description
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.
Time Frame
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
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
Description
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.
Time Frame
Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
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
Description
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.
Time Frame
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
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
Description
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.
Time Frame
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
C-reactive Protein (CRP): Mean Change From Baseline (Week 0) to Week 52
Description
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.
Time Frame
Baseline (Week 0) and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Number of Participants With Potentially Significant Hematology Parameters
Description
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.
Time Frame
52 weeks
Title
Number of Participants With Potentially Significant Clinical Chemistry Parameters
Description
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.
Time Frame
52 weeks
Title
Systolic Blood Pressure: Mean Change From Baseline (Week 0) to Each Visit
Description
Blood pressure was measured while the participant was sitting. n=the number of participants with available data at each time point.
Time Frame
Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Diastolic Blood Pressure: Mean Change From Baseline (Week 0) to Each Visit
Description
Blood pressure was measured while the participant was sitting. n=the number of participants with available data at each time point.
Time Frame
Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Heart Rate: Mean Change From Baseline (Week 0) to Each Visit
Description
Heart rate was measured while the participant was sitting. n=the number of participants with available data at each time point.
Time Frame
Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Body Temperature: Mean Change From Baseline (Week 0) to Each Visit
Description
n=the number of participants with available data at each time point.
Time Frame
Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
60 weeks
Other Pre-specified Outcome Measures:
Title
Change in Mean Serum Adalimumab Concentration From Baseline (Week 0) to Week 52
Description
Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated heterogeneous electrochemiluminescence (ECL)-immunoassay method. The assay captures adalimumab via biotinylated anti-idiotypic antibody, and detects it via sulfo-tagged TNF-alpha. n=the number of participants with available data at each time point.
Time Frame
Baseline (Week 0) to Week 52
Title
Change in Number of Subjects Positive for Anti-Adalimumab Antibodies (AAA) From Baseline to Week 52
Description
Serum samples with adalimumab concentration below 2 μg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 20 ng/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose.
Time Frame
Baseline (Week 0) to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morio Ozawa, MS
Organizational Affiliation
AbbVie GK.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
30221150
Citation
Motoya S, Watanabe M, Wallace K, Lazar A, Nishimura Y, Ozawa M, Thakkar R, Robinson AM, Singh RSP, Mostafa NM, Suzuki Y, Hibi T. Efficacy and Safety of Dose Escalation to Adalimumab 80 mg Every Other Week in Japanese Patients with Crohn's Disease Who Lost Response to Maintenance Therapy. Inflamm Intest Dis. 2018 Jul;2(4):228-235. doi: 10.1159/000486786. Epub 2018 May 15.
Results Reference
derived
Links:
URL
http://www.rxabbvie.com
Description
Related Info.
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A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease
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