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Safety and Efficacy of Andecaliximab in Participants With Moderately to Severely Active Crohn's Disease

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ClinicalTrials.gov Identifier: NCT02405442
Recruitment Status : Terminated
First Posted : April 1, 2015
Results First Posted : March 28, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE March 27, 2015
First Posted Date  ICMJE April 1, 2015
Results First Submitted Date  ICMJE March 5, 2019
Results First Posted Date  ICMJE March 28, 2019
Last Update Posted Date April 23, 2019
Actual Study Start Date  ICMJE April 30, 2015
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
  • Percentage of Participants Achieving Clinical Response (PRO2 Score ≤ 8) at Week 8 of the Double-Blind Phase [ Time Frame: Week 8 ]
    Clinical response was defined as patient-reported outcomes (PRO2) score ≤ 8 at Week 8. PRO2 is the weighted average of the 2 variables of frequency of liquid or very soft stool and abdominal pain, based on 7-day participant diary data. The PRO2 score has a minimum score of 0 and has no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with a missing PRO2 value at the Week 8 analysis visit were imputed as not achieving the Clinical Response.
  • Percentage of Participants Achieving Endoscopic Response (≥ 50% Reduction From Baseline SES-CD) at Week 8 of the Double-Blind Phase [ Time Frame: Week 8 ]
    Endoscopic response was defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 8. The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing SES-CD value at Week 8 analysis visit were imputed as not achieving Endoscopic Response.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Proportion of participants achieving clinical response at Week 8 [ Time Frame: Week 8 ]
  • Proportion of participants achieving endoscopic response at Week 8 [ Time Frame: Week 8 ]
Change History Complete list of historical versions of study NCT02405442 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
  • Percentage of Participants Achieving CDAI Remission (CDAI ≤ 150) at Week 8 of the Double-Blind Phase [ Time Frame: Week 8 ]
    Clinical remission was defined as Crohn's Disease Activity Index (CDAI) ≤ 150 at Week 8. CDAI is used as a measure of clinical response and remission. It includes 8 variables of patient-reported symptoms and objective variables: stool count, abdominal pain, general well-being, complications, use of anti-diarrheal medications, presence of abdominal mass, hematocrit values, and weight. It has a minimum range of 0 and no upper bound, with higher scores indicating greater disease activity. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing CDAI score at Week 8 analysis visit were imputed as not achieving CDAI Remission.
  • Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase [ Time Frame: Week 8 ]
    The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The SES-CD size-of-ulcer subscore ranges from 0 (none) to 3 (very large). Mucosal healing at Week 8 was defined as the size-of-ulcer subscore for segments with non-zero baseline value changes to zero at Week 8 AND the size-of-ulcer subscore for segments with zero value at baseline remain zero at Week 8. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing SES-CD size-of-ulcer subscore at Week 8 analysis visit were imputed as not achieving Mucosal Healing.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Proportion of participants achieving Crohn's Disease Activity Index (CDAI) remission at Week 8 [ Time Frame: Week 8 ]
  • Proportion of participants achieving mucosal healing at Week 8 [ Time Frame: Week 8 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Andecaliximab in Participants With Moderately to Severely Active Crohn's Disease
Official Title  ICMJE A Phase 2, Double-blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of GS-5745 in Subjects With Moderately to Severely Active Crohn's Disease
Brief Summary This study will primarily evaluate the safety and efficacy of andecaliximab in adults with active Crohn's disease. The study will consist of a Double-Blind Phase of 8 weeks followed by an Open-Label Extension. Participants who complete the Double-Blind Phase will be eligible to enroll in the optional Open-Label Extension for an additional 44 weeks. Participants who complete Week 52 assessments will be eligible to enter the Extended Treatment Phase to continue treatment with andecaliximab for an additional 156 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Andecaliximab
    Andecaliximab administered via subcutaneous (SC) injection
    Other Name: GS-5745
  • Drug: Placebo
    Placebo to match andecaliximab administered via SC injection
Study Arms  ICMJE
  • Experimental: Andecaliximab 150 mg Every 2 Weeks
    Double-Blind Phase: Participants will receive 1 single-use prefilled syringe (PFS) of andecaliximab 150 mg and matching placebo coadministered at Weeks 0, 2, 4, and 6 and 2 single-use PFS of placebo coadministered at Weeks 1, 3, 5, and 7. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.
    Interventions:
    • Drug: Andecaliximab
    • Drug: Placebo
  • Experimental: Andecaliximab 150 mg Weekly
    Double-Blind Phase: Participants will receive 1 single-use PFS of andecaliximab 150 mg and matching placebo coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.
    Interventions:
    • Drug: Andecaliximab
    • Drug: Placebo
  • Experimental: Andecaliximab 300 mg Weekly
    Double-Blind Phase: Participants will receive 2 single-use PFS of andecaliximab 150 mg coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.
    Intervention: Drug: Andecaliximab
  • Placebo Comparator: Placebo
    Double-Blind Phase: Participants will receive 2 single-use PFS of placebo coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.
    Interventions:
    • Drug: Andecaliximab
    • Drug: Placebo
Publications * Schreiber S, Siegel CA, Friedenberg KA, Younes ZH, Seidler U, Bhandari BR, Wang K, Wendt E, McKevitt M, Zhao S, Sundy JS, Lee SD, Loftus EV Jr. A phase 2, Randomized, Placebo-controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients with Moderately to Severely Active Crohn's Disease. J Crohns Colitis. 2018 May 29. doi: 10.1093/ecco-jcc/jjy070. [Epub ahead of print]

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: November 15, 2016)
187
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2015)
175
Actual Study Completion Date  ICMJE December 22, 2016
Actual Primary Completion Date November 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Ability to provide a written informed consent
  • Females of childbearing potential must have a negative pregnancy test at screening and baseline
  • Documented diagnosis of Crohn's disease with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum
  • Moderately to severely active Crohn's disease as defined by a Crohn's Disease Activity Index (CDAI) total score between 220-450 (inclusive) AND with evidence of active disease as measured by ileocolonoscopy
  • Within the previous 5 years, demonstrated an inadequate clinical response or intolerance of at least one of the following agents:

    • Corticosteroids
    • Immunomodulators
    • Tumor necrosis factor-alpha (TNFα) antagonists
    • Vedolizumab
  • May be receiving the following drugs:

    • Oral 5-aminosalicylate (5-ASA)
    • Oral corticosteroid therapy
    • Antidiarrheals for chronic diarrhea
    • Azathioprine or 6-mercaptopurine (6-MP) or methotrexate
    • Antibiotics for the treatment of Crohn's disease
  • Able to comply with the dosing instructions for study drug and able to comply with the study visits and requirements

Key Exclusion Criteria:

  • Evidence of abscess at screening
  • Extensive colonic resection (subtotal or total colectomy) or history of > 2 small bowel resections
  • Ileostomy, colostomy, or symptomatic stenosis of the intestine
  • Current use of oral corticosteroids at a dose equivalent to > 30 mg/day of prednisone
  • Ulcerative colitis or indeterminate colitis
  • Short bowel syndrome
  • Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli, Salmonella, Shigella, Campylobacter or Yersinia
  • Treatment with any monoclonal antibody within 4 weeks of screening
  • History or evidence of colonic mucosal dysplasia
  • HIV, hepatitis B, hepatitis C, or tuberculosis (TB) infection
  • Participated in a clinical study with an investigational drug or biologic within the last 30 days
  • Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the opinion of the investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

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 Australia,   Canada,   Czechia,   France,   Germany,   Hungary,   Italy,   New Zealand,   Poland,   South Africa,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Iceland
 
Administrative Information
NCT Number  ICMJE NCT02405442
Other Study ID Numbers  ICMJE GS-US-395-1663
2015-001249-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Team Gilead Sciences
PRS Account Gilead Sciences
Verification Date April 2019

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