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

Phase 2

Terminated

Conditions: Crohn's Disease

Interventions: Biological: Brodalumab
Drug: Placebo

Registration Number: NCT01150890

Lead Sponsor: Amgen

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 130

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Brodalumab 210 mg	Brodalumab	Participants received 210 mg brodalumab intravenously at baseline and week 4.
Brodalumab 350 mg	Brodalumab	Participants received 350 mg brodalumab intravenously at baseline and week 4.
Brodalumab 700 mg	Brodalumab	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Placebo	Placebo	Participants received placebo intravenously at baseline and week 4.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Clinical Remission at Week 6	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a CDAI Response at Week 6	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.
Time to Maximum Observed Concentration (Tmax) of Brodalumab	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.
Change From Baseline in CDAI at Week 6	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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 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.
Maximum Observed Concentration (Cmax) of Brodalumab	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.
Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab	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.
Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab	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.