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

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects With Moderate to Severe Crohn's Disease

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.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Biological: Brodalumab

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia
    • Research Site
  • Fitzroy, Australia
    • Research Site
  • Fremantle, Australia
    • Research Site
  • South Australia
    • Kurralta Park, South Australia, Australia
      • Research Site
• Belgium
  • Bonheiden, Belgium
    • Research Site
  • Gent, Belgium
    • Research Site
  • Leuven, Belgium
    • Research Site
  • Roeselare, Belgium
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Research Site
    • Victoria, British Columbia, Canada
      • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Research Site
    • London, Ontario, Canada
      • Research Site
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada
      • Research Site
• France
  • Lille cedex, France
    • Research Site
  • Nice Cedex 3, France
    • Research Site
  • Paris, France
    • Research Site
  • Paris Cedex 10, France
    • Research Site
  • Toulouse Cedex 09, France
    • Research Site
  • Vandoeuvre les Nancy, France
    • Research Site
• Netherlands
  • Amsterdam, Netherlands
    • Research Site
  • Maastricht, Netherlands
    • Research Site
  • Rotterdam, Netherlands
    • Research Site
• Poland
  • Bydgoszcz, Poland
    • Research Site
  • Olsztyn, Poland
    • Research Site
  • Opole, Poland
    • Research Site
  • Sopot, Poland
    • Research Site
• Spain
  • Barcelona, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Galicia
    • Pontevedra, Galicia, Spain
      • Research Site
    • Santiago de Compostela, Galicia, Spain
      • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
    • Dothan, Alabama, United States
      • Research Site
  • Arkansas
    • Lowell, Arkansas, United States
      • Research Site
  • Florida
    • Jacksonville, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
  • Louisiana
    • Hammond, Louisiana, United States
      • Research Site
  • Maryland
    • Chevy Chase, Maryland, United States
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States
      • Research Site
  • Missouri
    • Mexico, Missouri, United States
      • Research Site
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
      • Research Site
  • New York
    • Great Neck, New York, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
    • Wilmington, North Carolina, United States
      • Research Site
  • Tennessee
    • Germantown, Tennessee, United States
      • Research Site
    • Nashville, Tennessee, United States
      • Research Site
  • Texas
    • San Antonio, Texas, United States
      • Research Site
  • Utah
    • Logan, Utah, United States
      • Research Site
    • Ogden, Utah, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to initiating study drug
• Moderately to severely active Crohn's disease, as defined by a CDAI score >250 and < 450 at baseline
• Evidence of active inflammation

Exclusion Criteria:

• Short bowel syndrome
• Stricture with obstructive symptoms within 3 months
• Bowel surgery within 3 months
• Ileostomy and/or colostomy
• Any gastric or intestinal pouch
• Ulcerative colitis
• Evidence of an infected abscess
• Bowel perforation or evidence of noninflammatory obstruction during the 6 months
• Stool positive for C. Difficile toxin at screening
• Presence of active infection requiring treatment
• Serious infection within 8 weeks
• Significant concurrent medical conditions
• Pregnant or breast feeding
• Significant Laboratory abnormalities
• Any anti-tumor necrosis factor (TNF) agent within 2 months
• Steroid enemas within 2 weeks
• Tysabri (natalizumab) within 1 year
• Biologic agents (eg, ustekinumab), experimental procedures, or live vaccines within 3 months
• Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin),thalidomide or tacrolimus within 2 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo intravenously at baseline and week 4.	Drug: Placebo; Administered as as an intravenous (IV) infusion over at least 30 minutes.
Experimental: Brodalumab 210 mg; Participants received 210 mg brodalumab intravenously at baseline and week 4.	Biological: Brodalumab; Administered as as an intravenous (IV) infusion over at least 30 minutes.; Other Names: AMG 827
Experimental: Brodalumab 350 mg; Participants received 350 mg brodalumab intravenously at baseline and week 4.	Biological: Brodalumab; Administered as as an intravenous (IV) infusion over at least 30 minutes.; Other Names: AMG 827
Experimental: Brodalumab 700 mg; Participants received 700 mg brodalumab intravenously at baseline and week 4.	Biological: Brodalumab; Administered as as an intravenous (IV) infusion over at least 30 minutes.; Other Names: AMG 827

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Clinical Remission at 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.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a CDAI Response at 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.	Week 6
Change From Baseline in CDAI at 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.	Baseline and week 6
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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 hospitalization or prolongation of existing hospitalization,; resulted in persistent or significant disability/incapacity,; congenital anomaly/birth defect, and/or; other significant medical hazard. The investigator assessed whether each AE was possibly related to the study drug.	From first dose of study drug up to week 12.
Maximum Observed Concentration (Cmax) of Brodalumab	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 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.
Time to Maximum Observed Concentration (Tmax) of Brodalumab	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 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.
Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab	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 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.
Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab	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 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.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2010
• Primary Completion (Actual): October 15, 2011
• Study Completion (Actual): October 15, 2011

Study Registration Dates

• First Submitted: June 24, 2010
• First Submitted That Met QC Criteria: June 24, 2010
• First Posted (Estimate): June 25, 2010

Study Record Updates

• Last Update Posted (Actual): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Ileal Crohn's Disease; Ileo-colonic Crohn's Disease; Colonic Chron's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: 20090072; 2010-019544-39 (EudraCT Number)