Back to resultsStudy to Evaluate the Pharmacokinetics, Safety and Efficacy of Two Treatment Modules in Chinese Subjects With Moderate to Severe Crohn's Disease
Primary Purpose
Crohn's Disease
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Adalimumab
Placebo for adalimumab
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's Disease, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- Subjects of Chinese descent with full Chinese parentage.
- Diagnosis of Crohn's disease (CD) for at least 3 months prior to Week 0 confirmed by endoscopy, radiologic evaluation, and/or histology during the Screening Period.
- Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 despite treatment with oral corticosteroids and/or immunosuppressants.
- Subject has a negative Tuberculosis (TB) Screening Assessment.
Exclusion Criteria:
- Subject with ulcerative colitis or indeterminate colitis.
- Subject who has had a surgical bowel resection within the past 6 months or who is planning any resection at any time point in the future.
- Subject with an ostomy or ileoanal pouch.
- Subject who has short bowel syndrome.
- Subject with symptomatic known obstructive strictures.
- Subject with an internal or external fistula (with the exception of an anal fistula without abscess).
- Chronic recurring infections or active TB.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low Induction Dose
Standard Induction Dose
Arm Description
Participants received the low loading dose of adalimumab (80 mg at Week 0) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 2, 4, and 6.
Participants received the standard loading dose of adalimumab (160 mg at Week 0 and 80 mg at Week 2) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 4 and 6.
Outcomes
Primary Outcome Measures
Mean Serum Adalimumab Concentration at Week 8
Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Secondary Outcome Measures
Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) 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.
Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized.
Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab
Blood pressure and pulse were measured while the participant was sitting. The number of participants with a postbaseline vital sign result that meets Common Toxicity Criteria (CTC) version 3.0 (or later) Grade 3 or higher and is also more extreme than the baseline value is summarized. Terms abbreviated in the table include systolic blood pressure (SBP) and diastolic blood pressure (DBP). Increase and decrease are signified by ↑ and ↓, respectively.
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.
Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
CDAI: Mean Change From Baseline to Each Visit
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. Scores range from 0 to approximately 600. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Last observation carried forward (LOCF) for missing CDAI observations was used.
High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26
hsCRP 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 3 mg/L, slightly increasing with age. LOCF was used for missing data.
Fecal Calprotectin: Change From Baseline (Week 0) to Week 8
Stool samples for fecal calprotectin were collected before study drug administration when possible. Decreases in calprotectin are associated with decreased inflammation in the gastrointestinal tract. LOCF was used for missing data.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02015793
Brief Title
Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Two Treatment Modules in Chinese Subjects With Moderate to Severe Crohn's Disease
Official Title
A Phase 2, Randomized, Double-Blind, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Two Adalimumab Dosing Regimens in Chinese Subjects With Moderately to Severely Active Crohn's Disease and Elevated High-Sensitivity C-reactive Protein
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 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 of adalimumab following subcutaneous (SC) administration of 2 dosing regimens in Chinese subjects with Crohn's disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Crohn's Disease, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Induction Dose
Arm Type
Experimental
Arm Description
Participants received the low loading dose of adalimumab (80 mg at Week 0) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 2, 4, and 6.
Arm Title
Standard Induction Dose
Arm Type
Experimental
Arm Description
Participants received the standard loading dose of adalimumab (160 mg at Week 0 and 80 mg at Week 2) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 4 and 6.
Intervention Type
Biological
Intervention Name(s)
Adalimumab
Intervention Description
Adalimumab pre-filled syringe, administered by subcutaneous injection.
Intervention Type
Biological
Intervention Name(s)
Placebo for adalimumab
Intervention Description
Placebo for adalimumab pre-filled syringe, administered by subcutaneous injection to maintain double-blind.
Primary Outcome Measure Information:
Title
Mean Serum Adalimumab Concentration at Week 8
Description
Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab
Description
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) 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
26 weeks
Title
Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab
Description
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized.
Time Frame
From Week 0 to Week 26
Title
Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab
Description
Blood pressure and pulse were measured while the participant was sitting. The number of participants with a postbaseline vital sign result that meets Common Toxicity Criteria (CTC) version 3.0 (or later) Grade 3 or higher and is also more extreme than the baseline value is summarized. Terms abbreviated in the table include systolic blood pressure (SBP) and diastolic blood pressure (DBP). Increase and decrease are signified by ↑ and ↓, respectively.
Time Frame
26 weeks
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
35 weeks
Title
Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26
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 of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
Time Frame
Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Title
Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26
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 of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
Time Frame
Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Title
CDAI: Mean Change From Baseline to Each Visit
Description
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. Scores range from 0 to approximately 600. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Last observation carried forward (LOCF) for missing CDAI observations was used.
Time Frame
Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Title
High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26
Description
hsCRP 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 3 mg/L, slightly increasing with age. LOCF was used for missing data.
Time Frame
Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and 26
Title
Fecal Calprotectin: Change From Baseline (Week 0) to Week 8
Description
Stool samples for fecal calprotectin were collected before study drug administration when possible. Decreases in calprotectin are associated with decreased inflammation in the gastrointestinal tract. LOCF was used for missing data.
Time Frame
Baseline (Week 0) and Weeks 4 and 8
Other Pre-specified Outcome Measures:
Title
Number of Subjects Positive for Anti-Adalimumab Antibodies (AAA) From Baseline to Week 8
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 2 μg/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. No samples were tested because all samples had adalimumab concentrations >2 μg/mL.
Time Frame
Baseline (Week 0) to Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects of Chinese descent with full Chinese parentage.
Diagnosis of Crohn's disease (CD) for at least 3 months prior to Week 0 confirmed by endoscopy, radiologic evaluation, and/or histology during the Screening Period.
Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 despite treatment with oral corticosteroids and/or immunosuppressants.
Subject has a negative Tuberculosis (TB) Screening Assessment.
Exclusion Criteria:
Subject with ulcerative colitis or indeterminate colitis.
Subject who has had a surgical bowel resection within the past 6 months or who is planning any resection at any time point in the future.
Subject with an ostomy or ileoanal pouch.
Subject who has short bowel syndrome.
Subject with symptomatic known obstructive strictures.
Subject with an internal or external fistula (with the exception of an anal fistula without abscess).
Chronic recurring infections or active TB.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Robinson
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
27175116
Citation
Wu KC, Ran ZH, Gao X, Chen M, Zhong J, Sheng JQ, Kamm MA, Travis S, Wallace K, Mostafa NM, Shapiro M, Li Y, Thakkar RB, Robinson AM. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease. Intest Res. 2016 Apr;14(2):152-63. doi: 10.5217/ir.2016.14.2.152. Epub 2016 Apr 27.
Results Reference
result
Links:
URL
http://rxabbvie.com
Description
Related Info.
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Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Two Treatment Modules in Chinese Subjects With Moderate to Severe Crohn's Disease
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