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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01694485




Registration number
NCT01694485
Ethics application status
Date submitted
24/09/2012
Date registered
27/09/2012
Date last updated
27/06/2019

Titles & IDs
Public title
Abrilumab (AMG 181) in Adults With Moderate to Severe Ulcerative Colitis
Scientific title
A Randomized, Double Blind, Multiple Dose Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Ulcerative Colitis
Secondary ID [1] 0 0
2011-005251-13
Secondary ID [2] 0 0
20110166
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
Treatment: Other - Abrilumab
Treatment: Drugs - Placebo

Placebo comparator: Placebo Q4W/Abrilumab 210 mg Q3M - Participants received placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24.

During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

Experimental: Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M - Participants received 7 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24.

During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

Experimental: Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M - Participants received 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24.

During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

Experimental: Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M - Participants received 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24.

During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

Experimental: Abrilumab 210 mg/Abrilumab 210 mg Q3M - Participants received a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24.

During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.


Treatment: Other: Abrilumab
Administered by subcutaneous injection.

Treatment: Drugs: Placebo
Placebo matching to abrilumab administered by subcutaneous injection
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Remission at Week 8
Timepoint [1] 0 0
Week 8
Secondary outcome [1] 0 0
Percentage of Participants With Response at Week 8
Timepoint [1] 0 0
Baseline and week 8
Secondary outcome [2] 0 0
Percentage of Participants With Mucosal Healing at Week 8
Timepoint [2] 0 0
Week 8
Secondary outcome [3] 0 0
Percentage of Participants With Sustained Remission at Week 8 and Week 24
Timepoint [3] 0 0
Week 8 and week 24

Eligibility
Key inclusion criteria
* Diagnosis of ulcerative colitis (UC) established = 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report.
* Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score =2 prior to baseline
* Inadequate response to, loss of response to, or intolerance to at least one of the following treatments:

* Immunomodulators
* Anti-TNF agents
* Corticosteroids (non-US sites only).
* Neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Disease limited to the rectum (ie, within 10 cm of the anal verge)
* Toxic megacolon
* Crohn's Disease
* History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC
* Planned bowel surgery within 24 weeks from baseline
* Stool positive for C. Difficile toxin at screening
* History of gastrointestinal surgery within 8 weeks of baseline
* Primary Sclerosing Cholangitis
* Any uncontrolled or clinically significant systemic disease
* Condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluation, procedures or completion.
* Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV)
* Underlying condition that predisposes subject to infections (eg, uncontrolled diabetes; history of splenectomy)
* Known history of drug or alcohol abuse within 1 year of screening
* Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred > 5 years ago, subject is eligible with documentation of disease free state since treatment)
* Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline
* Prior exposure to anti tumor necrosis factor (TNF) agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline
* Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab
* Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline
* Use of intravenous or intramuscular corticosteroids within 2 weeks prior to screening and during screening
* Previously treated with AMG 181
* Received any type of live attenuated vaccine < 1 month prior to baseline or is planning to receive any such live attenuated vaccine over the course of the study
* Treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals
* Abnormal laboratory results at screening
* Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
* Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)

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 administering 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/04/2018
Sample size
Target
Accrual to date
Final
359
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Bankstown
Recruitment hospital [2] 0 0
Research Site - Concord
Recruitment hospital [3] 0 0
Research Site - Adelaide
Recruitment hospital [4] 0 0
Research Site - Box Hill
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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Arizona
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California
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Colorado
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Illinois
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Louisiana
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Michigan
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Minnesota
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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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Washington
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Austria
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Innsbruck
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Austria
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St Veit an der Glan
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Austria
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Wien
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Belgium
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Bonheiden
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Belgium
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Brussels
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Belgium
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Bruxelles
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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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Liège
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Canada
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Alberta
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British Columbia
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Manitoba
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Ontario
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Czechia
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Hradec Kralove
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Czechia
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Praha 4
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Czechia
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Praha 7
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Czechia
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Usti nad Labem
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Denmark
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Aalborg
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Herlev
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Denmark
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Hvidovre
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Denmark
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Køge
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Odense C
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Denmark
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Århus C
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Estonia
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Tallinn
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Estonia
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Tartu
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Amiens
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France
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Caen
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France
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Lille
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France
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Nice Cedex 3
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France
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Paris cedex 12
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France
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Pessac Cedex
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France
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Toulouse Cedex 9
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France
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Vandoeuvre les Nancy
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Germany
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Berlin
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Germany
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Frankfurt am Main
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Germany
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Halle (Saale)
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Germany
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Heidelberg
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Germany
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Kiel
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Greece
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Athens
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Greece
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Haidari
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Greece
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Heraklion
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Greece
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Larissa
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Greece
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Piraeus
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Hungary
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Bekescsaba
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Hungary
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Budapest
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Debrecen
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Miskolc
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Pecs
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Szeged
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Hungary
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Szekszard
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Italy
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Bologna
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Italy
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Firenze
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Italy
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Milano
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Italy
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Padova
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Italy
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Roma
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Italy
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Rozzano MI
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Latvia
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Riga
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Netherlands
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Amsterdam
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Breda
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Leiden
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Maastricht
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Rotterdam
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Norway
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Oslo
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Norway
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Tromsø
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Poland
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Bialystok
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Poland
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Bydgoszcz
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Poland
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Lodz
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Poland
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Warszawa
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Russian Federation
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Samara
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Russian Federation
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St. Petersburg
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Russian Federation
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St.-Petrsburg
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Russian Federation
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Stavropol
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Switzerland
State/province [91] 0 0
Basel
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Switzerland
State/province [92] 0 0
Bern
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Switzerland
State/province [93] 0 0
Zurich
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United Kingdom
State/province [94] 0 0
Birmingham
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United Kingdom
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Blackpool
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United Kingdom
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Coventry
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United Kingdom
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Derby
Country [98] 0 0
United Kingdom
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London
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United Kingdom
State/province [99] 0 0
Manchester
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Norwich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the effect of abrilumab on induction of remission in adults with moderate to severe ulcerative colitis after 8 weeks of treatment as assessed by a total Mayo Score = 2 points, with no individual subscore \> 1 point.
Trial website
https://clinicaltrials.gov/study/NCT01694485
Trial related presentations / publications
Sandborn WJ, Cyrille M, Hansen MB, Feagan BG, Loftus EV Jr, Rogler G, Vermeire S, Cruz ML, Yang J, Boedigheimer MJ, Abuqayyas L, Evangelista CM, Sullivan BA, Reinisch W. Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate-to-Severe Ulcerative Colitis. Gastroenterology. 2019 Mar;156(4):946-957.e18. doi: 10.1053/j.gastro.2018.11.035. Epub 2018 Nov 23.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
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/study/NCT01694485