Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn's Disease

Phase 3

Completed

Conditions: Crohn's Disease

Interventions: Drug: Adalimumab
Drug: Placebo

Registration Number: NCT02065570

Lead Sponsor: AbbVie

Brief Summary: This study will evaluate higher versus standard adalimumab dosing regimens for induction and maintenance therapy in subjects with moderately to severely active Crohn's Disease and evidence of mucosal ulceration.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 514

Inclusion Criteria

Diagnosis of Crohn's disease (CD) for at least 90 days, confirmed by endoscopy during the Screening Period.
Active CD with a Crohn's Disease Activity Index (CDAI) despite treatment with oral corticosteroids and/or immunosuppressants.
Mucosal ulceration on endoscopy.

Exclusion Criteria

Subject with ulcerative colitis or indeterminate colitis.
Subject who has had surgical bowel resections in the past 6 months or is planning resection.
Subjects with an ostomy or ileoanal pouch.
Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
Subject who has short bowel syndrome.
Chronic recurring infections or active Tuberculosis (TB).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction: Standard Induction Dose	Placebo	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.
Induction: Standard Induction Dose	Adalimumab	Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.
Induction: Higher Induction Dose	Adalimumab	Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
Maintenance: Clinically Adjusted (CA) Regimen	Adalimumab	Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.
Maintenance: Therapeutic Drug Monitoring (TDM) Regimen	Adalimumab	At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM will be determined by protocol-established dose adjustment criteria. Doses will be determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 will receive 40 mg ew.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Clinical Remission at Week 4	Week 4	Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants With Endoscopic Response at Week 12	Week 12	Endoscopic response was scored using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score \> 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).	Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. 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 subject and may require medical or surgical intervention to prevent any of the outcomes listed above. TEAEs: any event that began or worsened in severity after the first dose of study drug in the induction or maintenance study. Events with unknown severity were counted as severe. Events with unknown relationship to study drug were counted as drug-related.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12	Week 12	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.
Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12	Week 4 and Week 12	CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12	Week 12	Clinical response was scored using CDAI, which assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline. Endoscopic response was scored using the SES-CD, which evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score \>50% from Baseline (or for Baseline SES-CD of 4, at least a 2-point reduction from Baseline) at Week 12.
Percentage of Participants With Clinical Remission at Week 12	Week 12	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline	Week 12	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants With Endoscopic Remission at Week 12	Week 12	Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
Change From Baseline in Fecal Calprotectin Level at Week 4	Baseline, Week 4
Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4	Week 4
Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4	Week 4	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g and Endoscopic Remission at Week 12	Week 12	Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12	Week 12	The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 \[none\] to 3 \[very large\]; ulcerated surface ranging from 0 \[none\] to 3 \[\>30%\]; affected surface ranging from 0 \[none\] to 3 \[\>75%\], and narrowing ranging from 0 \[none\] to 3 \[cannot be passed\]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease.
Percentage of Participants With Clinical Response at Week 4	Week 4	Clinical response was scored using CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from baseline.
Percentage of Participants With Clinical Response at Week 12	Week 12	Clinical response was scored using CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline.
Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12	Week 12	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.
Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4	Week 4	The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8.

Trial Locations

Locations (143): Birmingham Gastroenterology Associates O.C /ID# 137282
🇺🇸
Birmingham, Alabama, United States
Digestive Health Specialists of the Southeast /ID# 122483
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Dothan, Alabama, United States
Moore UC San Diego Cancer Center /ID# 119053
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La Jolla, California, United States
Axis Clinical Trials /ID# 130390
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Los Angeles, California, United States
Rocky Mountain Gastroenterology /ID# 119038
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Wheat Ridge, Colorado, United States
Medical Research Ctr CT /ID# 119037
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Hamden, Connecticut, United States
Gastroenterology Group Naples /ID# 122493
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Naples, Florida, United States
Internal Med Specialists /ID# 137737
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Orlando, Florida, United States
Shafran Gastroenterology Ctr /ID# 119057
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Winter Park, Florida, United States
Winship Cancer Institute of Emory University /ID# 136851
🇺🇸
Atlanta, Georgia, United States
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Birmingham Gastroenterology Associates O.C /ID# 137282
🇺🇸Birmingham, Alabama, United States