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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Biological: Adalimumab; Biological: Placebo for adalimumab

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects of Chinese descent with full Chinese parentage.
2. 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.
3. Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 despite treatment with oral corticosteroids and/or immunosuppressants.
4. Subject has a negative Tuberculosis (TB) Screening Assessment.

Exclusion Criteria:

1. Subject with ulcerative colitis or indeterminate colitis.
2. 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.
3. Subject with an ostomy or ileoanal pouch.
4. Subject who has short bowel syndrome.
5. Subject with symptomatic known obstructive strictures.
6. Subject with an internal or external fistula (with the exception of an anal fistula without abscess).
7. Chronic recurring infections or active TB.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Positive for Anti-Adalimumab Antibodies (AAA) From Baseline to Week 8	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.	Baseline (Week 0) to Week 8

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Anne Robinson, AbbVie

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Crohn's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M14-232