Clinical trial NCT01696396: Abrilumab (AMG 181) in Adults With Moderate to Severe Crohn's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: IBD, Crohn's Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-10-01
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Remission at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants With Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants With Response at Week 12
timeFrame: Baseline and week 12
measure: Percentage of Participants With Response at Week 8
timeFrame: Baseline and week 8
measure: Percentage of Participants With Sustained Remission at Both Week 12 and Week 24
timeFrame: Week 12 and week 24
measure: Percentage of Participants With Sustained Remission at Both Week 8 and Week 24
timeFrame: Week 8 and week 24
measure: Change From Baseline in CDAI Score at Week 12
timeFrame: Baseline and week 12
measure: Change From Baseline in CDAI Score at Week 8
timeFrame: Baseline and week 8
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Dothan
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Goodyear
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Sanford
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Arlington Heights
country: United States
facility: Research Site
state: Illinois
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Chesterfield
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Mexico
country: United States
facility: Research Site
state: Missouri
city: Great Neck
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Hospital
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Mentor
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Innsbruck
country: Austria
facility: Research Site
city: St Veit an der Glan
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Bonheiden
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: London
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Praha 7
country: Czechia
facility: Research Site
city: Usti nad Labem
country: Czechia
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Herlev
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: Køge
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Århus C
country: Denmark
facility: Research Site
city: Amiens Cedex 1
country: France
facility: Research Site
city: Caen Cedex 9
country: France
facility: Research Site
city: Clichy
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Nice Cedex 3
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Paris cedex 12
country: France
facility: Research Site
city: Pessac Cedex
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Minden
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Bekescsaba
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Szekszard
country: Hungary
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Breda
country: Netherlands
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Torquay
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.