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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02405442




Registration number
NCT02405442
Ethics application status
Date submitted
27/03/2015
Date registered
1/04/2015
Date last updated
23/04/2019

Titles & IDs
Public title
Safety and Efficacy of Andecaliximab in Participants With Moderately to Severely Active Crohn's Disease
Scientific title
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
Secondary ID [1] 0 0
2015-001249-10
Secondary ID [2] 0 0
GS-US-395-1663
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Andecaliximab
Treatment: Drugs - Placebo

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.

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.

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.

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.


Treatment: Drugs: Andecaliximab
Andecaliximab administered via subcutaneous (SC) injection

Treatment: Drugs: Placebo
Placebo to match andecaliximab administered via SC injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Clinical Response (PRO2 Score = 8) at Week 8 of the Double-Blind Phase - 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.
Timepoint [1] 0 0
Week 8
Primary outcome [2] 0 0
Percentage of Participants Achieving Endoscopic Response (= 50% Reduction From Baseline SES-CD) at Week 8 of the Double-Blind Phase - 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.
Timepoint [2] 0 0
Week 8
Secondary outcome [1] 0 0
Percentage of Participants Achieving CDAI Remission (CDAI = 150) at Week 8 of the Double-Blind Phase - 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.
Timepoint [1] 0 0
Week 8
Secondary outcome [2] 0 0
Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase - 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.
Timepoint [2] 0 0
Week 8

Eligibility
Key inclusion criteria
Key

- 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 (TNFa) 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
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Footscray Hospital - Footscray
Recruitment hospital [5] 0 0
Gastroenterology/Colorectal Medicine & Genetics - Melbourne
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Bedford Park
Recruitment postcode(s) [4] 0 0
- Footscray
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
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Alabama
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Arizona
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Hradec Kralove 2
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Czechia
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Praha 7
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Lille
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Nantes
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Leipzig
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Germany
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Muenchen
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Bekescsaba
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Roma
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Rozzano
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Cambridge
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02405442
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Team
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02405442