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

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01150890
• Collaborator: (none)
• Enrollment: 130
• Locations: 51
• Arms: 4
• Actual Duration (Months): 11.2
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Biological: Brodalumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Nov 9, 2010
• Actual Primary Completion Date: Oct 15, 2011
• Actual Study Completion Date: Oct 15, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Dothan	Alabama	United States
3	Research Site	Lowell	Arkansas	United States
4	Research Site	Jacksonville	Florida	United States
5	Research Site	Miami	Florida	United States
6	Research Site	Hammond	Louisiana	United States
7	Research Site	Chevy Chase	Maryland	United States
8	Research Site	Rochester	Minnesota	United States
9	Research Site	Mexico	Missouri	United States
10	Research Site	Egg Harbor Township	New Jersey	United States
11	Research Site	Great Neck	New York	United States
12	Research Site	Charlotte	North Carolina	United States
13	Research Site	Wilmington	North Carolina	United States
14	Research Site	Germantown	Tennessee	United States
15	Research Site	Nashville	Tennessee	United States
16	Research Site	San Antonio	Texas	United States
17	Research Site	Logan	Utah	United States
18	Research Site	Ogden	Utah	United States
19	Research Site	Kurralta Park	South Australia	Australia
20	Research Site	Box Hill		Australia
21	Research Site	Fitzroy		Australia
22	Research Site	Fremantle		Australia
23	Research Site	Bonheiden		Belgium
24	Research Site	Gent		Belgium
25	Research Site	Leuven		Belgium
26	Research Site	Roeselare		Belgium
27	Research Site	Calgary	Alberta	Canada
28	Research Site	Vancouver	British Columbia	Canada
29	Research Site	Victoria	British Columbia	Canada
30	Research Site	Winnipeg	Manitoba	Canada
31	Research Site	Hamilton	Ontario	Canada
32	Research Site	London	Ontario	Canada
33	Research Site	Toronto	Ontario	Canada
34	Research Site	Montreal	Quebec	Canada
35	Research Site	Lille cedex		France
36	Research Site	Nice Cedex 3		France
37	Research Site	Paris Cedex 10		France
38	Research Site	Paris		France
39	Research Site	Toulouse Cedex 09		France
40	Research Site	Vandoeuvre les Nancy		France
41	Research Site	Amsterdam		Netherlands
42	Research Site	Maastricht		Netherlands
43	Research Site	Rotterdam		Netherlands
44	Research Site	Bydgoszcz		Poland
45	Research Site	Olsztyn		Poland
46	Research Site	Opole		Poland
47	Research Site	Sopot		Poland
48	Research Site	Pontevedra	Galicia	Spain
49	Research Site	Santiago de Compostela	Galicia	Spain
50	Research Site	Barcelona		Spain
51	Research Site	Madrid		Spain

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01150890
• Other Study ID Numbers: 20090072; 2010-019544-39
• First Posted: Jun 25, 2010
• Last Update Posted: Jan 3, 2022
• Last Verified: Nov 1, 2021

• Keywords provided by Amgen: Ileal Crohn's Disease; Ileo-colonic Crohn's Disease; Colonic Chron's Disease
• Additional relevant MeSH terms: Crohn Disease; Brodalumab

Study Results

Participant Flow

Recruitment Details	This study was conducted at 39 centers in Australia, Belgium, Canada, Spain, France, Netherlands, Poland, and the United States (US). A total of 212 subjects were screened and 130 participants were randomized.
Pre-assignment Detail	After completing all screening assessments and meeting all eligibility criteria, participants were randomized in a 1:1:1:1 ratio to one of four treatment groups.

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Period Title: Overall Study
STARTED	32	32	33	33
Received Study Drug	32	31	32	33
COMPLETED	28	19	21	16
NOT COMPLETED	4	13	12	17

Baseline Characteristics

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg	Total
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.	Total of all reporting groups
Overall Participants	32	32	33	33	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.8 (13.0)	32.8 (10.2)	36.8 (12.6)	36.7 (10.0)	35.8 (11.5)
Sex: Female, Male (Count of Participants)
Female	17 53.1%	19 59.4%	21 63.6%	21 63.6%	78 60%
Male	15 46.9%	13 40.6%	12 36.4%	12 36.4%	52 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	1 3%	1 3%	2 1.5%
Not Hispanic or Latino	25 78.1%	26 81.3%	26 78.8%	27 81.8%	104 80%
Unknown or Not Reported	7 21.9%	6 18.8%	6 18.2%	5 15.2%	24 18.5%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	1 3.1%	0 0%	0 0%	1 0.8%
Black or African American	0 0%	1 3.1%	0 0%	0 0%	1 0.8%
White	24 75%	23 71.9%	26 78.8%	27 81.8%	100 76.9%
Other	1 3.1%	1 3.1%	1 3%	1 3%	4 3.1%
Unknown	7 21.9%	6 18.8%	6 18.2%	5 15.2%	24 18.5%
Predominant Location of Crohn's Disease (CD) Involvement (Count of Participants)
Ileal	6 18.8%	5 15.6%	4 12.1%	3 9.1%	18 13.8%
Ileo-colonic	17 53.1%	19 59.4%	17 51.5%	16 48.5%	69 53.1%
Colonic	8 25%	7 21.9%	11 33.3%	13 39.4%	39 30%
Missing	0 0%	1 3.1%	0 0%	0 0%	1 0.8%
Unknown	1 3.1%	0 0%	1 3%	1 3%	3 2.3%
Duration of Crohn's Disease (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.38 (9.35)	9.57 (7.64)	14.21 (10.35)	11.71 (7.36)	11.75 (8.84)
Crohn's Disease Activity Index (CDAI) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	327.7 (63.0)	333.2 (61.9)	334.5 (60.3)	315.4 (54.0)	327.5 (59.6)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants; missing data were analyzed using the non-responder imputation method.

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	32	32	33	33
Number [percentage of participants]	3.1 9.7%	3.1 9.7%	15.2 46.1%	9.1 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg, Brodalumab 350 mg, Brodalumab 700 mg
	Comments	The primary null hypothesis was tested sequentially using a linear trend test at the significance level of 0.05 (two-sided) using logistic regression modeling.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1941
	Comments
	Method	Overall Trend test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.0000
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 350 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0966
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.1203
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 700 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3208
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.0597
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Achieved a CDAI Response at Week 6
Description	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 Frame	Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set; non-responder imputation was used.

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	32	31	33	33
Number [percentage of participants]	12.5 39.1%	16.1 50.3%	27.3 82.7%	15.2 46.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6831
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.0363
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 350 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1396
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.1477
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 700 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7588
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	0.0265
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in CDAI at Week 6
Description	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.
Time Frame	Baseline and week 6

Outcome Measure Data

Analysis Population Description

Full analysis set; missing CDAI scores were imputed using baseline values.

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	32	29	33	33
Mean (Standard Deviation) [score on a scale]	-28.2 (86.0)	-8.7 (95.3)	-35.4 (105.6)	-0.6 (105.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4161
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) model adjusted for baseline CDAI score.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 350 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8094
	Comments
	Method	ANCOVA
	Comments	ANCOVA model adjusted for baseline CDAI score.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 700 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3040
	Comments
	Method	ANCOVA
	Comments	ANCOVA model adjusted for baseline CDAI score.

4. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	From first dose of study drug up to week 12.

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who were randomized and received at least 1 dose of study drug.

Arm/Group Title	Placebo	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	32	31	32	33
All treatment emergent adverse events (TEAEs)	25 78.1%	23 71.9%	27 81.8%	28 84.8%
Serious adverse events	2 6.3%	3 9.4%	8 24.2%	9 27.3%
Fatal adverse events	0 0%	0 0%	0 0%	0 0%
TEAEs leading to discontinuation of study drug	1 3.1%	3 9.4%	3 9.1%	3 9.1%
TEAEs leading to discontinuation from study	0 0%	4 12.5%	3 9.1%	3 9.1%
Treatment-related treatment-emergent adverse events (TRTEAE)	10 31.3%	13 40.6%	21 63.6%	14 42.4%
Treatment-related serious adverse events	0 0%	3 9.4%	4 12.1%	5 15.2%
Treatment-related fatal adverse events	0 0%	0 0%	0 0%	0 0%
TRTEAE leading to discontinuation of study drug	1 3.1%	2 6.3%	2 6.1%	0 0%
TRTEAE leading to discontinuation from study	0 0%	2 6.3%	2 6.1%	0 0%

5. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Brodalumab
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

The PK analysis set includes participants in the PK substudy who received at least one dose of brodalumab and who provided valid drug concentration data at each sampling time point in Weeks 1 to 4, or in Week 5 to 12, and for whom at least one PK parameter or endpoint could be adequately estimated.

Arm/Group Title	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	5	8	10
After first dose	53.1 (6.40)	96.4 (17.6)	184 (64.9)
After second dose	54.5 (1.08)	98.7 (20.6)	171 (63.2)

6. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Brodalumab
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

The PK analysis set with available data

Arm/Group Title	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	5	8	10
After first dose	0.034	0.034	0.036
After second dose	0.031	0.033	0.029

7. Secondary Outcome

Title	Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

The PK analysis set with available data.

Arm/Group Title	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	5	8	10
After first dose	243 (61.0)	501 (190)	1428 (715)
After second dose	164 (124)	622 (330)	1558 (691)

8. Secondary Outcome

Title	Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

The PK analysis set with available data.

Arm/Group Title	Brodalumab 210 mg	Brodalumab 350 mg	Brodalumab 700 mg
Arm/Group Description	Participants received 210 mg brodalumab intravenously at baseline and week 4.	Participants received 350 mg brodalumab intravenously at baseline and week 4.	Participants received 700 mg brodalumab intravenously at baseline and week 4.
Measure Participants	5	8	10
After first dose	243 (61.0)	501 (190)	1432 (714)
After second dose	164 (124)	595 (268)	1434 (597)

Adverse Events

Time Frame	From first dose of study drug up to week 12.
Arm/Group Title	Placebo		Brodalumab 210 mg		Brodalumab 350 mg		Brodalumab 700 mg
Arm/Group Description	Participants received placebo intravenously at baseline and week 4.		Participants received 210 mg brodalumab intravenously at baseline and week 4.		Participants received 350 mg brodalumab intravenously at baseline and week 4.		Participants received 700 mg brodalumab intravenously at baseline and week 4.
All Cause Mortality
	Placebo		Brodalumab 210 mg		Brodalumab 350 mg		Brodalumab 700 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Brodalumab 210 mg		Brodalumab 350 mg		Brodalumab 700 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/32 (6.3%)		3/31 (9.7%)		8/32 (25%)		9/33 (27.3%)
Gastrointestinal disorders
Abdominal pain	0/32 (0%)		1/31 (3.2%)		2/32 (6.3%)		0/33 (0%)
Crohn's disease	1/32 (3.1%)		2/31 (6.5%)		5/32 (15.6%)		7/33 (21.2%)
Diarrhoea	0/32 (0%)		1/31 (3.2%)		1/32 (3.1%)		1/33 (3%)
Dysphagia	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Nausea	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Proctalgia	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Small intestinal obstruction	0/32 (0%)		0/31 (0%)		0/32 (0%)		1/33 (3%)
Vomiting	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
General disorders
Fatigue	0/32 (0%)		0/31 (0%)		0/32 (0%)		1/33 (3%)
Infections and infestations
Anal abscess	0/32 (0%)		1/31 (3.2%)		1/32 (3.1%)		1/33 (3%)
Gastroenteritis	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Pneumonia	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Fistula	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/32 (3.1%)		0/31 (0%)		0/32 (0%)		0/33 (0%)
Chronic obstructive pulmonary disease	0/32 (0%)		0/31 (0%)		0/32 (0%)		1/33 (3%)
Vascular disorders
Hypertension	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Brodalumab 210 mg		Brodalumab 350 mg		Brodalumab 700 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/32 (62.5%)		21/31 (67.7%)		23/32 (71.9%)		20/33 (60.6%)
Blood and lymphatic system disorders
Anaemia	2/32 (6.3%)		0/31 (0%)		0/32 (0%)		1/33 (3%)
Gastrointestinal disorders
Abdominal pain	3/32 (9.4%)		2/31 (6.5%)		3/32 (9.4%)		0/33 (0%)
Abdominal tenderness	2/32 (6.3%)		0/31 (0%)		2/32 (6.3%)		1/33 (3%)
Anal fissure	0/32 (0%)		1/31 (3.2%)		1/32 (3.1%)		3/33 (9.1%)
Anal fistula	1/32 (3.1%)		2/31 (6.5%)		0/32 (0%)		1/33 (3%)
Aphthous stomatitis	3/32 (9.4%)		1/31 (3.2%)		2/32 (6.3%)		0/33 (0%)
Crohn's disease	1/32 (3.1%)		6/31 (19.4%)		3/32 (9.4%)		2/33 (6.1%)
Diarrhoea	3/32 (9.4%)		0/31 (0%)		0/32 (0%)		0/33 (0%)
Dyspepsia	0/32 (0%)		2/31 (6.5%)		0/32 (0%)		2/33 (6.1%)
Gastrooesophageal reflux disease	0/32 (0%)		0/31 (0%)		2/32 (6.3%)		0/33 (0%)
Nausea	2/32 (6.3%)		1/31 (3.2%)		3/32 (9.4%)		4/33 (12.1%)
Proctalgia	0/32 (0%)		2/31 (6.5%)		1/32 (3.1%)		0/33 (0%)
Vomiting	1/32 (3.1%)		1/31 (3.2%)		1/32 (3.1%)		2/33 (6.1%)
General disorders
Fatigue	1/32 (3.1%)		1/31 (3.2%)		1/32 (3.1%)		2/33 (6.1%)
Pyrexia	4/32 (12.5%)		3/31 (9.7%)		8/32 (25%)		1/33 (3%)
Infections and infestations
Anal abscess	0/32 (0%)		0/31 (0%)		0/32 (0%)		2/33 (6.1%)
Gastroenteritis	2/32 (6.3%)		0/31 (0%)		1/32 (3.1%)		0/33 (0%)
Nasopharyngitis	0/32 (0%)		4/31 (12.9%)		0/32 (0%)		0/33 (0%)
Oral candidiasis	0/32 (0%)		2/31 (6.5%)		0/32 (0%)		1/33 (3%)
Oral herpes	1/32 (3.1%)		1/31 (3.2%)		2/32 (6.3%)		0/33 (0%)
Sinusitis	2/32 (6.3%)		0/31 (0%)		1/32 (3.1%)		1/33 (3%)
Upper respiratory tract infection	5/32 (15.6%)		0/31 (0%)		2/32 (6.3%)		0/33 (0%)
Urinary tract infection	0/32 (0%)		2/31 (6.5%)		0/32 (0%)		3/33 (9.1%)
Viral infection	0/32 (0%)		0/31 (0%)		0/32 (0%)		2/33 (6.1%)
Vulvovaginal mycotic infection	0/32 (0%)		0/31 (0%)		1/32 (3.1%)		2/33 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/32 (0%)		3/31 (9.7%)		2/32 (6.3%)		2/33 (6.1%)
Back pain	4/32 (12.5%)		3/31 (9.7%)		0/32 (0%)		2/33 (6.1%)
Nervous system disorders
Dysgeusia	1/32 (3.1%)		0/31 (0%)		3/32 (9.4%)		0/33 (0%)
Headache	5/32 (15.6%)		1/31 (3.2%)		2/32 (6.3%)		2/33 (6.1%)
Psychiatric disorders
Insomnia	0/32 (0%)		0/31 (0%)		4/32 (12.5%)		1/33 (3%)
Renal and urinary disorders
Proteinuria	0/32 (0%)		2/31 (6.5%)		0/32 (0%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/32 (0%)		0/31 (0%)		2/32 (6.3%)		1/33 (3%)
Oropharyngeal pain	1/32 (3.1%)		1/31 (3.2%)		2/32 (6.3%)		3/33 (9.1%)
Skin and subcutaneous tissue disorders
Dry skin	0/32 (0%)		0/31 (0%)		2/32 (6.3%)		2/33 (6.1%)
Rash	1/32 (3.1%)		1/31 (3.2%)		2/32 (6.3%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.