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

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ClinicalTrials.gov Identifier: NCT02065570
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : February 18, 2021
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE February 17, 2014
First Posted Date  ICMJE February 19, 2014
Results First Submitted Date  ICMJE January 20, 2021
Results First Posted Date  ICMJE February 18, 2021
Last Update Posted Date February 18, 2021
Actual Study Start Date  ICMJE May 1, 2014
Actual Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • Percentage of Participants Who Achieved Clinical Remission at Week 4 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • Proportion of subject who achieve clinical remission [ Time Frame: At Week 4 ]
    Clinical remission will be scored using Crohn's Disease Activity Index (CDAI).
  • Proportion of subjects who achieve endoscopic improvement [ Time Frame: At Week 12 ]
    Endoscopic improvement will be scored using Simplified Endoscopic Score for Crohn's Disease (SES CD).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 4 ]
  • Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4 [ Time Frame: Week 4 ]
  • Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4 [ Time Frame: 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.
  • Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12 [ Time Frame: 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 Achieving Response in IBDQ Fatigue Item at Week 12 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • Proportion of subjects that show clinical remission [ Time Frame: At Week 12 ]
    Clinical remission will be scored using Crohn's Disease Activity Index (CDAI).
  • Proportion of subjects who discontinued corticosteroid use and achieved clinical remission [ Time Frame: At Week 12 ]
    Clinical remission will be scored using Crohn's Disease Activity Index (CDAI).
  • Change in proportion of subjects with clinical response [ Time Frame: From Week 4 to Week 12 ]
    Clinical response will be scored measuring for a decrease in Crohn's Disease Activity Index (CDAI).
  • Proportion of subjects with endoscopic response [ Time Frame: At Week 12 ]
    Endoscopic improvement will be scored using Simplified Endoscopic Score for Crohn's Disease (SES CD).
  • Change in Inflammatory Bowel disease Questionnaire (IBDQ) [ Time Frame: From Week 0 to Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn's Disease
Official Title  ICMJE A Multicenter, Randomized, Double-Blind Study to 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Adalimumab
    Other Name: Humira
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Induction: Standard Induction Dose
    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.
    Interventions:
    • Drug: Adalimumab
    • Drug: Placebo
  • Experimental: Induction: Higher Induction Dose
    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.
    Intervention: Drug: Adalimumab
  • Experimental: Maintenance: Clinically Adjusted (CA) Regimen
    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.
    Intervention: Drug: Adalimumab
  • Experimental: Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
    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.
    Intervention: Drug: Adalimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 30, 2018)
514
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2014)
310
Actual Study Completion Date  ICMJE January 30, 2020
Actual Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Austria,   Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Hungary,   Israel,   Netherlands,   Poland,   Puerto Rico,   Romania,   Slovakia,   Spain,   Switzerland,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02065570
Other Study ID Numbers  ICMJE M14-115
2013-001746-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP