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NCT01696396

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

Completed Phase 2 Results posted Last updated 27 June 2019
What this trial tests

Phase 2 trial testing Abrilumab in Crohn's Disease in 254 participants. Completed in 10 April 2018.

Timeline
4 December 2012
Primary endpoint
26 December 2014
10 April 2018

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment254
Start date4 December 2012
Primary completion26 December 2014
Estimated completion10 April 2018
Sites84 locations across Denmark, France, Netherlands, Belgium, Austria, United Kingdom, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 65, any sex, with Crohn's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Remission at Week 8 Primary · 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 o

Unadjusted remission rate
GroupValue95% CI
Placebo13.3
Abrilumab 21 mg Q4W23.1
Abrilumab 70 mg Q4W14.3
Abrilumab 210 mg19.5
Adjusted remission rate
GroupValue95% CI
Placebo12.8
Abrilumab 21 mg Q4W23.1
Abrilumab 70 mg Q4W14.4
Abrilumab 210 mg21.9
Percentage of Participants With Remission at Week 12 Secondary · 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 dat

Unadjusted remission rate
GroupValue95% CI
Placebo18.1
Abrilumab 21 mg Q4W33.3
Abrilumab 70 mg Q4W25.3
Abrilumab 210 mg27.0
Adjusted remission rate
GroupValue95% CI
Placebo20.1
Abrilumab 21 mg Q4W43.8
Abrilumab 70 mg Q4W31.0
Abrilumab 210 mg34.8
Percentage of Participants With Response at Week 12 Secondary · Baseline and 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

Unadjusted response rate
GroupValue95% CI
Placebo27.7
Abrilumab 21 mg Q4W41.7
Abrilumab 70 mg Q4W45.3
Abrilumab 210 mg43.2
Adjusted response rate
GroupValue95% CI
Placebo35.3
Abrilumab 21 mg Q4W50.4
Abrilumab 70 mg Q4W55.1
Abrilumab 210 mg50.9
Percentage of Participants With Response at Week 8 Secondary · Baseline and 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

Unadjusted response rate
GroupValue95% CI
Placebo26.4
Abrilumab 21 mg Q4W33.3
Abrilumab 70 mg Q4W42.9
Abrilumab 210 mg30.6
Adjusted response rate
GroupValue95% CI
Placebo30.6
Abrilumab 21 mg Q4W33.8
Abrilumab 70 mg Q4W46.6
Abrilumab 210 mg32.6
Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 Secondary · 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

Unadjusted remission rate
GroupValue95% CI
Placebo8.2
Abrilumab 21 mg Q4W19.2
Abrilumab 70 mg Q4W11.9
Abrilumab 210 mg17.1
Adjusted remission rate
GroupValue95% CI
Placebo9.0
Abrilumab 21 mg Q4W25.0
Abrilumab 70 mg Q4W14.0
Abrilumab 210 mg21.7
Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 Secondary · 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.

Unadjusted remission rate
GroupValue95% CI
Placebo7.1
Abrilumab 21 mg Q4W15.4
Abrilumab 70 mg Q4W9.5
Abrilumab 210 mg12.2
Adjusted remission rate
GroupValue95% CI
Placebo5.9
Abrilumab 21 mg Q4W14.3
Abrilumab 70 mg Q4W8.7
Abrilumab 210 mg12.7
Change From Baseline in CDAI Score at Week 12 Secondary · Baseline and 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.

GroupValue95% CI
Placebo-55.32± 11.41
Abrilumab 21 mg Q4W-92.16± 21.85
Abrilumab 70 mg Q4W-97.41± 12.92
Abrilumab 210 mg-96.11± 22.78
Change From Baseline in CDAI Score at Week 8 Secondary · Baseline and 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.

GroupValue95% CI
Placebo-64.05± 9.62
Abrilumab 21 mg Q4W-80.42± 20.86
Abrilumab 70 mg Q4W-91.52± 11.78
Abrilumab 210 mg-87.64± 19.89

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug to week 24 in the double-blind period and from first dose of study drug in the open-label period to 12 weeks after last dose in the open-label period (up to 108 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DB Period: Placebo
Serious: 14/98 (14%)
Deaths:
DB Period: Abrilumab 21 mg Q4W
Serious: 7/25 (28%)
Deaths:
DB Period: Abrilumab 70 mg Q4W
Serious: 13/85 (15%)
Deaths:
DB Period: Abrilumab 210 mg
Serious: 6/41 (15%)
Deaths:
OL Period: Placebo/Abrilumab 210 mg Q3M
Serious: 24/84 (29%)
Deaths:
OL Period: Abrilumab 21 mg Q4W/210 mg Q3M
Serious: 3/20 (15%)
Deaths:
OL Period: Abrilumab 70 mg Q4W/210 mg Q3M
Serious: 19/76 (25%)
Deaths:
Period: Abrilumab 210 mg/210 mg Q3M
Serious: 12/37 (32%)
Deaths:

Serious adverse events (69 terms)

ReactionSystemDB Period: PlaceboDB Period: Abrilumab 21 mg…DB Period: Abrilumab 70 mg…DB Period: Abrilumab 210 mgOL Period: Placebo/Abrilum…OL Period: Abrilumab 21 mg…OL Period: Abrilumab 70 mg…Period: Abrilumab 210 mg/2…
Crohn's diseaseGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Anal abscessInfections and infestations
Ileal stenosisGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Cardiac arrestCardiac disorders
Myocardial infarctionCardiac disorders
Myocardial ischaemiaCardiac disorders
Abdominal herniaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain lowerGastrointestinal disorders
Anal fistulaGastrointestinal disorders
Chronic gastritisGastrointestinal disorders
ConstipationGastrointestinal disorders
EnteritisGastrointestinal disorders
Enterocolonic fistulaGastrointestinal disorders
IleusGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Large intestine perforationGastrointestinal disorders
Adverse drug reactionGeneral disorders
ChillsGeneral disorders
Influenza like illnessGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
PyrexiaGeneral disorders
Other adverse events (75 terms — click to expand)

ReactionSystemDB Period: PlaceboDB Period: Abrilumab 21 mg…DB Period: Abrilumab 70 mg…DB Period: Abrilumab 210 mgOL Period: Placebo/Abrilum…OL Period: Abrilumab 21 mg…OL Period: Abrilumab 70 mg…Period: Abrilumab 210 mg/2…
Crohn's diseaseGastrointestinal disorders
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
InfluenzaInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Influenza like illnessGeneral disorders
GastroenteritisInfections and infestations
Upper respiratory tract infectionInfections and infestations
DizzinessNervous system disorders
ParaesthesiaNervous system disorders
Urinary tract infectionInfections and infestations
RashSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
InsomniaPsychiatric disorders
FatigueGeneral disorders
Anal abscessInfections and infestations
BronchitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
Anal fistulaGastrointestinal disorders
Oedema peripheralGeneral disorders
SinusitisInfections and infestations
Viral infectionInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
ConstipationGastrointestinal disorders
ProctalgiaGastrointestinal disorders
ToothacheGastrointestinal disorders
MalaiseGeneral disorders
PainGeneral disorders
Clostridium difficile infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Zinc deficiencyMetabolism and nutrition disorders

Most-reported serious reactions: Crohn's disease, Small intestinal obstruction, Anal abscess, Ileal stenosis, Anaemia, Acute myocardial infarction, Cardiac arrest, Myocardial infarction.

Data from ClinicalTrials.gov NCT01696396 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting integrin pathways: mechanisms and advances in therapy.
    Pang X, He X, Qiu Z, Zhang H, et al · · 2023 · cited 704× · PMID 36588107 · DOI 10.1038/s41392-022-01259-6
  2. Integrin-based therapeutics: biological basis, clinical use and new drugs.
    Ley K, Rivera-Nieves J, Sandborn WJ, Shattil S. · · 2016 · cited 321× · PMID 26822833 · DOI 10.1038/nrd.2015.10
  3. Dissecting Innate and Adaptive Immunity in Inflammatory Bowel Disease: Immune Compartmentalization, Microbiota Crosstalk, and Emerging Therapies.
    Yue N, Hu P, Tian C, Kong C, et al · · 2024 · cited 9× · PMID 39634289 · DOI 10.2147/jir.s492079
  4. T cell trafficking in human chronic inflammatory diseases.
    Giovenzana A, Codazzi V, Pandolfo M, Petrelli A. · · 2024 · cited 5× · PMID 39171290 · DOI 10.1016/j.isci.2024.110528
  5. The Role and Application of MAdCAM-1/α4β7-Induced Lymphocyte Migration in Inflammatory Enterohepatic Diseases.
    Yu C, Pan Y, Mao A, Zhao Y, et al · · 2025 · PMID 41301753 · DOI 10.3390/biomedicines13112659

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing