Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Two Treatment Modules in Chinese Subjects With Moderate to Severe Crohn's Disease

Phase 2

Completed

Conditions: Crohn's Disease

Interventions: Biological: Adalimumab
Biological: Placebo for adalimumab

Registration Number: NCT02015793

Lead Sponsor: AbbVie

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Induction Dose	Placebo for adalimumab	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.
Standard Induction Dose	Adalimumab	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.
Low Induction Dose	Adalimumab	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.

Primary Outcome Measures

Name	Time	Method
Mean Serum Adalimumab Concentration at Week 8	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

Name	Time	Method
Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab	26 weeks	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.
Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26	Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 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.
Fecal Calprotectin: Change From Baseline (Week 0) to Week 8	Baseline (Week 0) and Weeks 4 and 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.
High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26	Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and 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.
Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26	Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 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.
Number of Participants With Adverse Events (AEs)	35 weeks	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.
Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab	From Week 0 to Week 26	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.
CDAI: Mean Change From Baseline to Each Visit	Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26	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.
Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab	26 weeks	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.