Abrilumab (AMG 181) in Adults With Moderate to Severe Crohn's Disease

Crohn's Disease Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01696396
• Other study ID #: 20110232
• Secondary ID: 2012-000529-31
• Status: Completed
• Phase: Phase 2
• Start date: December 4, 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 efficacy of abrilumab as measured by the proportion of participants achieving Crohn's Disease Activity Index (CDAI) remission (CDAI < 150) after treatment for 8 weeks.

Description:

The study consisted of a 24-week double-blind treatment period, a 108-week open-label treatment period, and a 2-year safety follow-up period.

Participants who did not reach minimal improvement, or experienced disease worsening after initial response, had the option to receive open-label abrilumab 210 mg every 3 months (Q3M) beginning at double-blind period week 12 or after. Not reaching minimal improvement was defined as not having an improvement in CDAI score of ≥ 70 points from baseline on 2 consecutive visits (at or after week 8) at least 2 weeks apart. Disease worsening after week 8 (or week 12) response was defined as having an increase in CDAI score of ≥ 70 points from the week 8 (or week 12) CDAI score on 2 consecutive visits at least 2 weeks apart, and a CDAI score of > 150.

Participants were planned to be randomized in a 2:1:2:1 ratio to SC placebo or abrilumab at 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 3:2:1. 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: 254
• Est. completion date: April 10, 2018
• Est. primary completion date: December 26, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to baseline

• Moderately to severely active Crohn's disease defined by a CDAI score = 220 and = 450 at baseline

• Evidence of active inflammation within 12 weeks prior to baseline

• Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: Immunomodulators and/or anti-tumor necrosis factor (TNF) agents or to 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

• Subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening

Exclusion Criteria:

• Short bowel syndrome

• Stricture with obstructive symptoms within 3 months

• Bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline

• Ileostomy and/or colostomy

• Any gastric or intestinal pouch

• Evidence of an infected abscess

• Bowel perforation or evidence of non-inflammatory obstruction during the 6 months prior to baseline

• Stool positive for C. difficile toxin at screening

• Any uncontrolled or clinically significant systemic disease

• Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV)

• Any underlying condition that predisposes subject to infections

• Subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline

• Received an anti-TNF agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods.

• Any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies, AMG 181, or any form of cell-based transplantation

• Received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals

• Significant laboratory abnormalities

• Pregnant or breast feeding

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Abrilumab
Administered by subcutaneous injection.
• Placebo
Placebo matching to abrilumab administered by subcutaneous injection

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Austria	Research Site	St Veit an der Glan
Austria	Research Site	Wien
Austria	Research Site	Wien
Belgium	Research Site	Bonheiden
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
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 4
Czechia	Research Site	Praha 5
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
France	Research Site	Amiens Cedex 1
France	Research Site	Caen Cedex 9
France	Research Site	Clichy
France	Research Site	Lille
France	Research Site	Nice Cedex 3
France	Research Site	Paris Cedex 10
France	Research Site	Paris cedex 12
France	Research Site	Pessac Cedex
France	Research Site	Vandoeuvre les Nancy
Germany	Research Site	Hamburg
Germany	Research Site	Leipzig
Germany	Research Site	Minden
Germany	Research Site	Stuttgart
Hungary	Research Site	Bekescsaba
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Miskolc
Hungary	Research Site	Szekszard
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Leiden
Netherlands	Research Site	Maastricht
Netherlands	Research Site	Rotterdam
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Zurich
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Norwich
United Kingdom	Research Site	Torquay
United States	Research Site	Ann Arbor	Michigan
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	Goodyear	Arizona
United States	Research Site	Great Neck	New York
United States	Research Site	Greenville	North Carolina
United States	Research Site	Jacksonville	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Mentor	Ohio
United States	Research Site	Mexico	Missouri
United States	Research Site	Mobile	Alabama
United States	Hospital	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Rochester	Minnesota
United States	Research Site	Sanford	Florida
United States	Research Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Netherlands,  Switzerland,  United Kingdom, 

References & Publications (1)

Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017 Jun;66(6):683-695. doi: 10.1007/s00262-017-1967-1. Epub 2017 Feb 25. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Remission at Week 8	Remission was defined as a Crohn's Disease Activity Index (CDAI) score < 150 at week 8.; The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI Score (adjusted remission rate).	Week 8
Secondary	Percentage of Participants With Remission at Week 12	Remission was defined as a Crohn's Disease Activity Index (CDAI) score < 150. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI Score (adjusted remission rate).	Week 12
Secondary	Percentage of Participants With Response at Week 12	Response was defined as either remission (a CDAI score < 150) or a decrease from baseline in the CDAI score of = 100 points.; The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI score (adjusted response rate).	Baseline and week 12
Secondary	Percentage of Participants With Response at Week 8	Response was defined as either remission (a CDAI score < 150) or a decrease from baseline in the CDAI score of = 100 points.; The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI score (adjusted response rate).	Baseline and week 8
Secondary	Percentage of Participants With Sustained Remission at Both Week 12 and Week 24	Remission was defined as a Crohn's Disease Activity Index (CDAI) score < 150. Sustained remission was defined as achieving the criteria for remission at both week 12 and week 24.; The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI Score (adjusted remission rate).	Week 12 and week 24
Secondary	Percentage of Participants With Sustained Remission at Both Week 8 and Week 24	Remission was defined as a Crohn's Disease Activity Index (CDAI) score < 150. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24.; The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.; 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 CDAI Score (adjusted remission rate).	Week 8 and week 24
Secondary	Change From Baseline in CDAI Score at Week 12	The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.	Baseline and week 12
Secondary	Change From Baseline in CDAI Score at Week 8	The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.	Baseline and week 8

External Links

•   AmgenTrials clinical trials website