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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: Brodalumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ileal Crohn's Disease, Ileo-colonic Crohn's Disease, Colonic Chron's Disease