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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02520284




Registration number
NCT02520284
Ethics application status
Date submitted
7/08/2015
Date registered
11/08/2015
Date last updated
10/04/2019

Titles & IDs
Public title
Safety and Efficacy of Andecaliximab (GS-5745) in Adults With Moderately to Severely Active Ulcerative Colitis
Scientific title
A Combined Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluating the Safety and Efficacy of GS-5745 in Subjects With Moderately to Severely Active Ulcerative Colitis
Secondary ID [1] 0 0
2014-005217-24
Secondary ID [2] 0 0
GS-US-326-1100
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Andecaliximab
Other interventions - Placebo

Experimental: Andecaliximab Every 2 Weeks - Participants will receive andecaliximab 150 mg administered via subcutaneous (SC) injection alternating with matching placebo weekly for a total of 4 doses of andecaliximab. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.

Experimental: Andecaliximab Weekly - Participants will receive andecaliximab 150 mg administered via SC injection once weekly for a total of 8 doses. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.

Placebo Comparator: Placebo - Participants will receive placebo matched to andecaliximab administered via SC injection once weekly for a total of 8 doses. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.


Other interventions: Andecaliximab
Andecaliximab 150 mg administered via SC injection

Other interventions: Placebo
Placebo matched to andecaliximab administered via SC injection

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
For Cohort 1, Percentage of Participants With EBS Clinical Remission at Week 8 - EBS clinical remission was defined as an endoscopic subscore of 0 or 1 (endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]); rectal bleeding subscore of 0 (rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes); and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 (stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal).
Timepoint [1] 0 0
Week 8
Secondary outcome [1] 0 0
For Cohort 1, Percentage of Participants With MCS Remission at Week 8 - The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and physician's global assessment (PGA). The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. The MCS remission was defined as a MCS of = 2 points and no individual subscore > 1 point. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
Timepoint [1] 0 0
Week 8
Secondary outcome [2] 0 0
For Cohort 1, Percentage of Participants With MCS Response at Week 8 - The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and PGA. The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening. The MCS response was defined as a MCS reduction of = 3 points and at least 30% from baseline, with an accompanying decrease in rectal bleeding subscore of = 1 point or an absolute rectal bleeding subscore of 0 or 1.
Timepoint [2] 0 0
Week 8
Secondary outcome [3] 0 0
For Cohort 1, Percentage of Participants With Endoscopic Remission at Week 8 - Endoscopic remission was defined as endoscopic subscore of 0. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
Timepoint [3] 0 0
Week 8
Secondary outcome [4] 0 0
For Cohort 1, Percentage of Participants With Endoscopic Response at Week 8 - Endoscopic response was defined as endoscopic subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
Timepoint [4] 0 0
Week 8
Secondary outcome [5] 0 0
For Cohort 1, Percentage of Participants With Mucosal Healing as Determined by the Geboes Histologic Scoring System at Week 8 - Mucosal healing was defined as elimination of ulcers/erosion, elimination of crypt destruction, elimination of intraepithelial neutrophils, elimination of lamina propria neutrophils, and reduction in lamina propria chronic inflammatory cells to at most a mild increase. When measured by the Geboes histologic scoring system, it was the selection of the following combined scores of = 3 for Grade 0 (Structural Architectural Change), = 1 for Grade 1 (Chronic Inflammatory Infiltrate), = 3 for Grade 2A (Lamina Propria Eosinophils), and 0 for Grade 2B (Lamina Propria Neutrophils), Grade 3 (Neutrophils in Epithelium), Grade 4 (Crypt Destruction), and Grade 5 (Erosion or Ulceration). Total Geboes histologic score ranged from 0 to 22, with higher scores indicating greater disease severity.
Timepoint [5] 0 0
Week 8
Secondary outcome [6] 0 0
For Cohort 1, Percentage of Participants With MCS Remission (Alternative Definition) at Week 8 - The MCS remission (alternative definition) was defined as a rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and PGA subscore (range: 0 to 3 with higher score indicating the severe disease) of 0, and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]) of 0 or 1 for an overall MCS of = 1. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
Timepoint [6] 0 0
Week 8

Eligibility
Key inclusion criteria
Key

- Ulcerative Colitis (UC) confirmed on endoscopy

- Moderately to severely active UC (Mayo Score 6-12)

- May be receiving oral 5-aminosalicylate (ASA), oral corticosteroid, azathioprine,
6-mercaptopurine (MP), or methotrexate

- Treatment failure with at least one of the following agents received: corticosteroids,
immunomodulators, tumor necrosis factor-alpha (TNFa) antagonists, vedolizumab

Key
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Diagnose of Crohn's disease or indeterminate colitis

- Pregnant or lactating females

- Any chronic medical condition (including, but not limited to cardiac or pulmonary
disease, alcohol or drug abuse)

- Exhibit severe UC / clinically significant active infection

- History of malignancy in the last 5 years

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/Phase 3
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)
Recruitment hospital [1] 0 0
- Footscray
Recruitment hospital [2] 0 0
- Herston
Recruitment hospital [3] 0 0
- Malvern
Recruitment hospital [4] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Footscray
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Malvern
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Colorado
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Florida
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Illinois
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Kansas
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Kentucky
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Louisiana
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Michigan
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Minnesota
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Mouscron
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Pleven
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Canada
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British Columbia
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Canada
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Ontario
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Czechia
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Hradec Kralove
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France
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Nantes
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Hungary
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Bekescsaba
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Hungary
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Budapest
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Hungary
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Debrecen
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Ireland
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Leinster
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Italy
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Rozzano
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Italy
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San Giovanni Rotondo
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Korea, Republic of
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Seoul
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Korea, Republic of
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Suwon-si
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Latvia
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Daugavpils
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Netherlands
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Amsterdam
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New Zealand
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Canterbury Region
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New Zealand
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Auckland
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New Zealand
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Wellington
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Bialystok
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Krakow
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Lublin
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Piaseczno
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Poznan
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Sopot
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Sroda Wielkopolska
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Tychy
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Warszawa
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Wroclaw
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Romania
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Bucharest
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Romania
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Timisoara
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Russian Federation
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Moscow
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Russian Federation
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Novosibirsk
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Slovakia
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Trencin
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South Africa
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Western Cape
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Switzerland
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Basel
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Switzerland
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Bern
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Taiwan
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Taichung
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Ukraine
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Kharkov
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Ukraine
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Kyiv
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Lviv
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Ukraine
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Odessa
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Ukraine
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Vinnitsa
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United Kingdom
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Cambridge
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Oxford
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United Kingdom
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Prescot

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are as follows: 1) To evaluate the efficacy of
andecaliximab to induce endoscopy, rectal bleeding, and stool frequency (EBS) clinical
remission at Week 8 (Cohort 1); 2) To evaluate the efficacy of andecaliximab to maintain EBS
clinical remission at Week 52 (Cohort 2); and 3) To evaluate the safety and tolerability of
andecaliximab. The study will consist of 3 parts: Induction Phase (Cohort 1), Maintenance
Phase (Cohort 2), and an optional Extended Treatment Phase.
Trial website
https://clinicaltrials.gov/show/NCT02520284
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
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/NCT02520284