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NCT01150890

Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease

Terminated Phase 2 Results posted Last updated 3 January 2022
What this trial tests

Phase 2 trial testing Brodalumab in Crohn's Disease in 130 participants. Terminated before completion.

Timeline
9 November 2010
Primary endpoint
15 October 2011
15 October 2011

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment130
Start date9 November 2010
Primary completion15 October 2011
Estimated completion15 October 2011
Sites50 locations across France, Netherlands, Belgium, Poland, Canada, Australia, United States, Spain

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 Who Achieved Clinical Remission at Week 6 Primary · Week 6

Clinical remission is defined by a CDAI score of ≤ 150 points. The CDAI measures the severity of active disease using 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). The CDAI score is calculated by summing weighted scores for each item. CDAI scores range from 0 to 600, with higher scores indicating greater disease activity.

GroupValue95% CI
Placebo3.1
Brodalumab 210 mg3.1
Brodalumab 350 mg15.2
Brodalumab 700 mg9.1
Percentage of Participants Who Achieved a CDAI Response at Week 6 Secondary · Week 6

CDAI response is defined as a reduction from baseline in CDAI score of ≥ 100 points. The CDAI measures the severity of active disease using 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). The CDAI score is calculated by summing weighted scores for each item. CDAI scores range from 0 to 600, with higher scores indicating greater disease activity.

GroupValue95% CI
Placebo12.5
Brodalumab 210 mg16.1
Brodalumab 350 mg27.3
Brodalumab 700 mg15.2
Change From Baseline in CDAI at Week 6 Secondary · Baseline and week 6

The CDAI measures the severity of active disease using 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). The CDAI score is calculated by summing weighted scores for each item. CDAI scores range from 0 to 600, with higher scores indicating greater disease activity. A negative change from baseline indicates improvement.

GroupValue95% CI
Placebo-28.2± 86.0
Brodalumab 210 mg-8.7± 95.3
Brodalumab 350 mg-35.4± 105.6
Brodalumab 700 mg-0.6± 105.9
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · From first dose of study drug up to week 12.

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. A treatment-emergent AE is an event that occurred after the initiation of study drug or was already present prior to the initiation of study drug but worsened in either intensity or frequency after the initiation of study drug. A serious AE is an adverse event that met at least one of the following criteria: * fatal, * life threatening, * required in-patient hospitaliz

All treatment emergent adverse events (TEAEs)
GroupValue95% CI
Placebo25
Brodalumab 210 mg23
Brodalumab 350 mg27
Brodalumab 700 mg28
Serious adverse events
GroupValue95% CI
Placebo2
Brodalumab 210 mg3
Brodalumab 350 mg8
Brodalumab 700 mg9
Fatal adverse events
GroupValue95% CI
Placebo0
Brodalumab 210 mg0
Brodalumab 350 mg0
Brodalumab 700 mg0
TEAEs leading to discontinuation of study drug
GroupValue95% CI
Placebo1
Brodalumab 210 mg3
Brodalumab 350 mg3
Brodalumab 700 mg3
TEAEs leading to discontinuation from study
GroupValue95% CI
Placebo0
Brodalumab 210 mg4
Brodalumab 350 mg3
Brodalumab 700 mg3
Treatment-related treatment-emergent adverse events (TRTEAE)
GroupValue95% CI
Placebo10
Brodalumab 210 mg13
Brodalumab 350 mg21
Brodalumab 700 mg14
Treatment-related serious adverse events
GroupValue95% CI
Placebo0
Brodalumab 210 mg3
Brodalumab 350 mg4
Brodalumab 700 mg5
Treatment-related fatal adverse events
GroupValue95% CI
Placebo0
Brodalumab 210 mg0
Brodalumab 350 mg0
Brodalumab 700 mg0
Maximum Observed Concentration (Cmax) of Brodalumab Secondary · After first dose on Day 1 (pre-dose and within 15 minutes after the end of infusion [EOI]), day 4-6, 15, and 29 (pre-dose) and after second dose on day 29 (pre-dose and within 15 minutes after EOI), days 32-34, 43, 57, 64-66, and 85.

An optional pharmacokinetic (PK) substudy was offered to participants at a subset of sites and required additional informed consent. Serum concentrations of brodalumab were measured using a validated analytical method, enzyme-linked immusosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay was 0.0500 μg/mL.

After first dose
GroupValue95% CI
Brodalumab 210 mg53.1± 6.40
Brodalumab 350 mg96.4± 17.6
Brodalumab 700 mg184± 64.9
After second dose
GroupValue95% CI
Brodalumab 210 mg54.5± 1.08
Brodalumab 350 mg98.7± 20.6
Brodalumab 700 mg171± 63.2
Time to Maximum Observed Concentration (Tmax) of Brodalumab Secondary · After first dose on Day 1 (pre-dose and within 15 minutes after the end of infusion [EOI]), day 4-6, 15, and 29 (pre-dose) and after second dose on day 29 (pre-dose and within 15 minutes after EOI), days 32-34, 43, 57, 64-66, and 85.

An optional pharmacokinetic (PK) substudy was offered to participants at a subset of sites and required additional informed consent. Serum concentrations of brodalumab were measured using a validated analytical method, enzyme-linked immusosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay was 0.0500 μg/mL.

After first dose
GroupValue95% CI
Brodalumab 210 mg0.0340.028 – 0.22
Brodalumab 350 mg0.0340.021 – 0.050
Brodalumab 700 mg0.0360.024 – 0.047
After second dose
GroupValue95% CI
Brodalumab 210 mg0.0310.026 – 0.039
Brodalumab 350 mg0.0330.024 – 0.042
Brodalumab 700 mg0.0290.024 – 0.039
Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab Secondary · After first dose on Day 1 (pre-dose and within 15 minutes after the end of infusion [EOI]), day 4-6, 15, and 29 (pre-dose) and after second dose on day 29 (pre-dose and within 15 minutes after EOI), days 32-34, 43, 57, 64-66, and 85.

An optional pharmacokinetic (PK) substudy was offered to participants at a subset of sites and required additional informed consent. Serum concentrations of brodalumab were measured using a validated analytical method, enzyme-linked immusosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay was 0.0500 μg/mL.

After first dose
GroupValue95% CI
Brodalumab 210 mg243± 61.0
Brodalumab 350 mg501± 190
Brodalumab 700 mg1428± 715
After second dose
GroupValue95% CI
Brodalumab 210 mg164± 124
Brodalumab 350 mg622± 330
Brodalumab 700 mg1558± 691
Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab Secondary · After first dose on Day 1 (pre-dose and within 15 minutes after the end of infusion [EOI]), day 4-6, 15, and 29 (pre-dose) and after second dose on day 29 (pre-dose and within 15 minutes after EOI), days 32-34, 43, and 57.

An optional pharmacokinetic (PK) substudy was offered to participants at a subset of sites and required additional informed consent. Serum concentrations of brodalumab were measured using a validated analytical method, enzyme-linked immusosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay was 0.0500 μg/mL.

After first dose
GroupValue95% CI
Brodalumab 210 mg243± 61.0
Brodalumab 350 mg501± 190
Brodalumab 700 mg1432± 714
After second dose
GroupValue95% CI
Brodalumab 210 mg164± 124
Brodalumab 350 mg595± 268
Brodalumab 700 mg1434± 597

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to week 12.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/32 (6%)
Deaths:
Brodalumab 210 mg
Serious: 3/31 (10%)
Deaths:
Brodalumab 350 mg
Serious: 8/32 (25%)
Deaths:
Brodalumab 700 mg
Serious: 9/33 (27%)
Deaths:

Serious adverse events (16 terms)

ReactionSystemPlaceboBrodalumab 210 mgBrodalumab 350 mgBrodalumab 700 mg
Crohn's diseaseGastrointestinal disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
NauseaGastrointestinal disorders
ProctalgiaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Anal abscessInfections and infestations
GastroenteritisInfections and infestations
PneumoniaInfections and infestations
FistulaMusculoskeletal and connective tissue disorders
AsthmaRespiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Other adverse events (35 terms — click to expand)

ReactionSystemPlaceboBrodalumab 210 mgBrodalumab 350 mgBrodalumab 700 mg
PyrexiaGeneral disorders
Crohn's diseaseGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
NauseaGastrointestinal disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Abdominal painGastrointestinal disorders
Anal fissureGastrointestinal disorders
Aphthous stomatitisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal tendernessGastrointestinal disorders
Anal fistulaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
ProctalgiaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Anal abscessInfections and infestations
GastroenteritisInfections and infestations
Oral candidiasisInfections and infestations
Oral herpesInfections and infestations
SinusitisInfections and infestations
Viral infectionInfections and infestations
Vulvovaginal mycotic infectionInfections and infestations
ProteinuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Crohn's disease, Abdominal pain, Diarrhoea, Dysphagia, Nausea, Proctalgia, Small intestinal obstruction, Vomiting.

Data from ClinicalTrials.gov NCT01150890 adverse events section.

Sponsor's own description

The study will examine the safety and effectiveness of brodalumab for the treatment of moderate to severe Crohn's disease. Participants will randomly assigned to receive either brodalumab or placebo (a lookalike liquid that doesn't have any drug in it) and neither the doctor nor the patient will know what treatment is being given.

Publications & conference data

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

  1. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing.
    Gaffen SL, Jain R, Garg AV, Cua DJ. · · 2014 · cited 1246× · PMID 25145755 · DOI 10.1038/nri3707
  2. Interactions between neutrophils and T-helper 17 cells.
    Fan X, Shu P, Wang Y, Ji N, et al · · 2023 · cited 51× · PMID 37920459 · DOI 10.3389/fimmu.2023.1279837
  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

Verify or expand the search:

Other trials of Brodalumab

Trials testing the same drug.

Other recruiting trials for Crohn's Disease

Currently open trials in the same condition.

Other Amgen trials

Trials by the same sponsor.

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