Abrilumab (AMG 181) in Adults With Moderate to Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01694485
• Other study ID #: 20110166
• Secondary ID: 2011-005251-13
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2012
• Est. completion date: April 10, 2018

Study information

• Verified date: May 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study consisted of a 24-week double-blind, placebo-controlled treatment period followed by an open-label period of approximately 108 weeks. Participants were eligible to enter the open-label period of the study early if they did not achieve a response at week 8 and had an inadequate response at week 12 or later or if they experienced disease worsening after achieving response and/or remission at week 8. Failure to achieve response at week 8 was defined as failure to achieve a decrease from baseline in total Mayo Score ≥ 3 points and ≥ 30% decrease from baseline. Inadequate response at week 12 or later was defined as failure to achieve a 2-point decrease and 25% improvement in partial Mayo Score compared with screening and minimum partial Mayo Score ≥ 5 points. Disease worsening was defined as an increase in partial Mayo Score ≥ 3 points from the week 8 value and minimum partial Mayo Score ≥ 5 points with recto-sigmoidoscopy sub-score ≥ 2.

Participants were planned to be randomized in a 2:1:2:2:2 ratio to placebo or abrilumab at 7 mg, 21 mg, 70 mg (on day 1, week 2, week 4, and every 4 weeks thereafter until week 24), or 210 mg (on day 1 followed by placebo in weeks 2 and 4 and every 4 weeks thereafter until week 24), respectively. Due to a consistent discrepancy between the investigational product (IP) instruction manual (IPIM) description of vial positions and the actual vial positions in the IP package participants were initially randomized to 3 arms (placebo, 70 mg, and 210 mg) with a randomization ratio of 4:3:2. The study was temporarily paused while this issue was investigated. Once the discrepancy was corrected, Protocol Amendment 3 implemented, and affected participants completed their double-blind treatment period, the study resumed enrollment and randomization per protocol. Neither the randomization nor study blind was compromised and therefore the intent-to-treat principle was maintained.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 359
• Est. completion date: April 10, 2018
• Est. primary completion date: July 13, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

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)

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• Abrilumab
Administered by subcutaneous injection.

Drug:
• Placebo
Placebo matching to abrilumab administered by subcutaneous injection

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Bankstown	New South Wales
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Concord	New South Wales
Austria	Research Site	Innsbruck
Austria	Research Site	St Veit an der Glan
Austria	Research Site	Wien
Belgium	Research Site	Bonheiden
Belgium	Research Site	Brussels
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Winnipeg	Manitoba
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 7
Czechia	Research Site	Usti nad Labem
Denmark	Research Site	Aalborg
Denmark	Research Site	Århus C
Denmark	Research Site	Herlev
Denmark	Research Site	Hvidovre
Denmark	Research Site	Køge
Denmark	Research Site	Odense C
Estonia	Research Site	Tallinn
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Amiens
France	Research Site	Caen
France	Research Site	Lille
France	Research Site	Nice Cedex 3
France	Research Site	Paris cedex 12
France	Research Site	Pessac Cedex
France	Research Site	Toulouse Cedex 9
France	Research Site	Vandoeuvre les Nancy
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Halle (Saale)
Germany	Research Site	Heidelberg
Germany	Research Site	Kiel
Greece	Research Site	Athens
Greece	Research Site	Haidari
Greece	Research Site	Heraklion
Greece	Research Site	Larissa
Greece	Research Site	Piraeus
Hungary	Research Site	Bekescsaba
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Miskolc
Hungary	Research Site	Miskolc
Hungary	Research Site	Pecs
Hungary	Research Site	Szeged
Hungary	Research Site	Szekszard
Italy	Research Site	Bologna
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Rozzano MI
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Leiden
Netherlands	Research Site	Maastricht
Netherlands	Research Site	Rotterdam
Norway	Research Site	Oslo
Norway	Research Site	Tromsø
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Lodz
Poland	Research Site	Lodz
Poland	Research Site	Lodz
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Samara
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.-Petrsburg
Russian Federation	Research Site	Stavropol
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Zurich
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Blackpool
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Derby
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Norwich
United States	Research Site	Arlington Heights	Illinois
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chesterfield	Michigan
United States	Research Site	Dothan	Alabama
United States	Research Site	Germantown	Tennessee
United States	Research Site	Great Neck	New York
United States	Research Site	Greenville	North Carolina
United States	Research Site	Hammond	Louisiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Lone Tree	Colorado
United States	Research Site	Mentor	Ohio
United States	Research Site	Miami	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	Naples	Florida
United States	Research Site	New York	New York
United States	Research Site	Rochester	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Torrance	California
United States	Research Site	Urbana	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Hungary,  Italy,  Latvia,  Netherlands,  Norway,  Poland,  Russian Federation,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Remission at Week 8	Remission was defined as a total Mayo Score = 2 points, with no individual subscore > 1 point.; The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.; The remission rate (percentage of participants with remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted remission rate).	Week 8
Secondary	Percentage of Participants With Response at Week 8	Response was defined by a decrease from baseline in the total Mayo Score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore = 1 point or an absolute rectal bleeding subscore = 0 or 1.; The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, ranging from 0 to 12 points. Higher scores represent more severe disease.; The response rate (percentage of participants with response) was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted response rate).	Baseline and week 8
Secondary	Percentage of Participants With Mucosal Healing at Week 8	Mucosal healing was defined using the rectosigmoidoscopy subscore of Mayo assessment as absolute subscore for rectosigmoidoscopy of 0 or 1.; Flexible rectosigmoidoscopy was performed as part of the Mayo assessment, graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status.; The healing rate (percentage of participants with mucosal healing) was calculated based on observed data (unadjusted healing rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline rectosigmoidoscopy score (adjusted healing rate).	Week 8
Secondary	Percentage of Participants With Sustained Remission at Week 8 and Week 24	Remission was defined as a total Mayo Score = 2 points, with no individual subscore > 1 point. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24.; The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher scores represent more severe disease status. The total Mayo Score is the sum of the four item scores, with a and ranges from 0 to 12 points. Higher scores represent more severe disease.; The remission rate (percentage of participants with sustained remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted remission rate).	Week 8 and week 24

External Links

•   AmgenTrials clinical trials website