Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Two Treatment Modules in Chinese Subjects With Moderate to Severe 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 of adalimumab following subcutaneous (SC) administration of 2 dosing regimens in Chinese subjects with Crohn's disease.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Adalimumab
* Biological: Placebo for adalimumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Induction Dose<br>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. | Biological: Adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection.<br>Biological: Placebo for adalimumab<br>* Placebo for adalimumab pre-filled syringe, administered by subcutaneous injection to maintain double-blind.<br>|
| Experimental: Standard Induction Dose<br>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. | Biological: Adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 26 weeks | 
| 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. | From Week 0 to Week 26 | 
| 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. | 26 weeks | 
| 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. | 35 weeks | 
| 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. | Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | 
| 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. | Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | 
| 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. | Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | 
| 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. | Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and 26 | 
| 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. | Baseline (Week 0) and Weeks 4 and 8 | 

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