Trial Outcomes & Findings for Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease (NCT NCT01150890)

Last Updated: 2022-01-03

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

130 participants

Primary outcome timeframe

Week 6

Results posted on

2022-01-03

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Overall Study STARTED	32	32	33	33
Overall Study Received Study Drug	32	31	32	33
Overall Study COMPLETED	28	19	21	16
Overall Study NOT COMPLETED	4	13	12	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Overall Study Other	0	1	0	2
Overall Study Pregnancy	0	0	0	1
Overall Study Administrative Decision	4	4	5	6
Overall Study Ineligibility determined	0	1	0	0
Overall Study Adverse Event	0	0	2	0
Overall Study Withdrawal by Subject	0	0	2	1
Overall Study Disease progression	0	7	3	7

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=32 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=32 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=33 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 Participants Participants received 700 mg brodalumab intravenously at baseline and week 4.	Total n=130 Participants Total of all reporting groups
Age, Continuous	36.8 years STANDARD_DEVIATION 13.0 • n=32 Participants	32.8 years STANDARD_DEVIATION 10.2 • n=32 Participants	36.8 years STANDARD_DEVIATION 12.6 • n=33 Participants	36.7 years STANDARD_DEVIATION 10.0 • n=33 Participants	35.8 years STANDARD_DEVIATION 11.5 • n=130 Participants
Sex: Female, Male Female	17 Participants n=32 Participants	19 Participants n=32 Participants	21 Participants n=33 Participants	21 Participants n=33 Participants	78 Participants n=130 Participants
Sex: Female, Male Male	15 Participants n=32 Participants	13 Participants n=32 Participants	12 Participants n=33 Participants	12 Participants n=33 Participants	52 Participants n=130 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=32 Participants	0 Participants n=32 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	2 Participants n=130 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=32 Participants	26 Participants n=32 Participants	26 Participants n=33 Participants	27 Participants n=33 Participants	104 Participants n=130 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=32 Participants	6 Participants n=32 Participants	6 Participants n=33 Participants	5 Participants n=33 Participants	24 Participants n=130 Participants
Race/Ethnicity, Customized Asian	0 Participants n=32 Participants	1 Participants n=32 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	1 Participants n=130 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=32 Participants	1 Participants n=32 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	1 Participants n=130 Participants
Race/Ethnicity, Customized White	24 Participants n=32 Participants	23 Participants n=32 Participants	26 Participants n=33 Participants	27 Participants n=33 Participants	100 Participants n=130 Participants
Race/Ethnicity, Customized Other	1 Participants n=32 Participants	1 Participants n=32 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	4 Participants n=130 Participants
Race/Ethnicity, Customized Unknown	7 Participants n=32 Participants	6 Participants n=32 Participants	6 Participants n=33 Participants	5 Participants n=33 Participants	24 Participants n=130 Participants
Predominant Location of Crohn's Disease (CD) Involvement Ileal	6 Participants n=32 Participants	5 Participants n=32 Participants	4 Participants n=33 Participants	3 Participants n=33 Participants	18 Participants n=130 Participants
Predominant Location of Crohn's Disease (CD) Involvement Ileo-colonic	17 Participants n=32 Participants	19 Participants n=32 Participants	17 Participants n=33 Participants	16 Participants n=33 Participants	69 Participants n=130 Participants
Predominant Location of Crohn's Disease (CD) Involvement Colonic	8 Participants n=32 Participants	7 Participants n=32 Participants	11 Participants n=33 Participants	13 Participants n=33 Participants	39 Participants n=130 Participants
Predominant Location of Crohn's Disease (CD) Involvement Missing	0 Participants n=32 Participants	1 Participants n=32 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	1 Participants n=130 Participants
Predominant Location of Crohn's Disease (CD) Involvement Unknown	1 Participants n=32 Participants	0 Participants n=32 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	3 Participants n=130 Participants
Duration of Crohn's Disease	11.38 years STANDARD_DEVIATION 9.35 • n=32 Participants • Participants with available data	9.57 years STANDARD_DEVIATION 7.64 • n=31 Participants • Participants with available data	14.21 years STANDARD_DEVIATION 10.35 • n=33 Participants • Participants with available data	11.71 years STANDARD_DEVIATION 7.36 • n=32 Participants • Participants with available data	11.75 years STANDARD_DEVIATION 8.84 • n=128 Participants • Participants with available data
Crohn's Disease Activity Index (CDAI)	327.7 score on a scale STANDARD_DEVIATION 63.0 • n=32 Participants • Participants with available data	333.2 score on a scale STANDARD_DEVIATION 61.9 • n=29 Participants • Participants with available data	334.5 score on a scale STANDARD_DEVIATION 60.3 • n=33 Participants • Participants with available data	315.4 score on a scale STANDARD_DEVIATION 54.0 • n=33 Participants • Participants with available data	327.5 score on a scale STANDARD_DEVIATION 59.6 • n=127 Participants • Participants with available data

PRIMARY outcome

Timeframe: Week 6

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

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=32 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=33 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 Participants Participants received 700 mg brodalumab intravenously at baseline and week 4.
Percentage of Participants Who Achieved Clinical Remission at Week 6	3.1 percentage of participants	3.1 percentage of participants	15.2 percentage of participants	9.1 percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: Full analysis set; non-responder imputation was used.

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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=31 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=33 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 Participants Participants received 700 mg brodalumab intravenously at baseline and week 4.
Percentage of Participants Who Achieved a CDAI Response at Week 6	12.5 percentage of participants	16.1 percentage of participants	27.3 percentage of participants	15.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and week 6

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=29 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=33 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 Participants Participants received 700 mg brodalumab intravenously at baseline and week 4.
Change From Baseline in CDAI at Week 6	-28.2 score on a scale Standard Deviation 86.0	-8.7 score on a scale Standard Deviation 95.3	-35.4 score on a scale Standard Deviation 105.6	-0.6 score on a scale Standard Deviation 105.9

SECONDARY outcome

Timeframe: From first dose of study drug up to week 12.

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=31 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=32 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 Participants Participants received 700 mg brodalumab intravenously at baseline and week 4.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) All treatment emergent adverse events (TEAEs)	25 Participants	23 Participants	27 Participants	28 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious adverse events	2 Participants	3 Participants	8 Participants	9 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Fatal adverse events	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAEs leading to discontinuation of study drug	1 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAEs leading to discontinuation from study	0 Participants	4 Participants	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related treatment-emergent adverse events (TRTEAE)	10 Participants	13 Participants	21 Participants	14 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related serious adverse events	0 Participants	3 Participants	4 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related fatal adverse events	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TRTEAE leading to discontinuation of study drug	1 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TRTEAE leading to discontinuation from study	0 Participants	2 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=8 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=10 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Maximum Observed Concentration (Cmax) of Brodalumab After second dose	54.5 μg/mL Standard Deviation 1.08	98.7 μg/mL Standard Deviation 20.6	171 μg/mL Standard Deviation 63.2	—
Maximum Observed Concentration (Cmax) of Brodalumab After first dose	53.1 μg/mL Standard Deviation 6.40	96.4 μg/mL Standard Deviation 17.6	184 μg/mL Standard Deviation 64.9	—

SECONDARY outcome

Population: The PK analysis set with available data

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=8 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=10 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Time to Maximum Observed Concentration (Tmax) of Brodalumab After second dose	0.031 days Interval 0.026 to 0.039	0.033 days Interval 0.024 to 0.042	0.029 days Interval 0.024 to 0.039	—
Time to Maximum Observed Concentration (Tmax) of Brodalumab After first dose	0.034 days Interval 0.028 to 0.22	0.034 days Interval 0.021 to 0.05	0.036 days Interval 0.024 to 0.047	—

SECONDARY outcome

Population: The PK analysis set with available data.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=8 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=10 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab After first dose	243 day*μg/mL Standard Deviation 61.0	501 day*μg/mL Standard Deviation 190	1428 day*μg/mL Standard Deviation 715	—
Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab After second dose	164 day*μg/mL Standard Deviation 124	622 day*μg/mL Standard Deviation 330	1558 day*μg/mL Standard Deviation 691	—

SECONDARY outcome

Population: The PK analysis set with available data.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=8 Participants Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=10 Participants Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4.
Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab After first dose	243 day*μg/mL Standard Deviation 61.0	501 day*μg/mL Standard Deviation 190	1432 day*μg/mL Standard Deviation 714	—
Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab After second dose	164 day*μg/mL Standard Deviation 124	595 day*μg/mL Standard Deviation 268	1434 day*μg/mL Standard Deviation 597	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Brodalumab 210 mg

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Brodalumab 350 mg

Serious events: 8 serious events

Other events: 23 other events

Deaths: 0 deaths

Brodalumab 700 mg

Serious events: 9 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=32 participants at risk Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=31 participants at risk Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=32 participants at risk Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 participants at risk Participants received 700 mg brodalumab intravenously at baseline and week 4.
Gastrointestinal disorders Abdominal pain	0.00% 0/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Crohn's disease	3.1% 1/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	15.6% 5/32 • From first dose of study drug up to week 12.	21.2% 7/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Diarrhoea	0.00% 0/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Dysphagia	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Nausea	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Proctalgia	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Vomiting	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
General disorders Fatigue	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Infections and infestations Anal abscess	0.00% 0/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Infections and infestations Gastroenteritis	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Infections and infestations Pneumonia	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Respiratory, thoracic and mediastinal disorders Asthma	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Vascular disorders Hypertension	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.

Measure	Placebo n=32 participants at risk Participants received placebo intravenously at baseline and week 4.	Brodalumab 210 mg n=31 participants at risk Participants received 210 mg brodalumab intravenously at baseline and week 4.	Brodalumab 350 mg n=32 participants at risk Participants received 350 mg brodalumab intravenously at baseline and week 4.	Brodalumab 700 mg n=33 participants at risk Participants received 700 mg brodalumab intravenously at baseline and week 4.
Blood and lymphatic system disorders Anaemia	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Abdominal pain	9.4% 3/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	9.4% 3/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Abdominal tenderness	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Anal fissure	0.00% 0/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	9.1% 3/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Anal fistula	3.1% 1/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Aphthous stomatitis	9.4% 3/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Crohn's disease	3.1% 1/32 • From first dose of study drug up to week 12.	19.4% 6/31 • From first dose of study drug up to week 12.	9.4% 3/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Diarrhoea	9.4% 3/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Dyspepsia	0.00% 0/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Nausea	6.2% 2/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	9.4% 3/32 • From first dose of study drug up to week 12.	12.1% 4/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Proctalgia	0.00% 0/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Gastrointestinal disorders Vomiting	3.1% 1/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
General disorders Fatigue	3.1% 1/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
General disorders Pyrexia	12.5% 4/32 • From first dose of study drug up to week 12.	9.7% 3/31 • From first dose of study drug up to week 12.	25.0% 8/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Infections and infestations Anal abscess	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Infections and infestations Gastroenteritis	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Infections and infestations Nasopharyngitis	0.00% 0/32 • From first dose of study drug up to week 12.	12.9% 4/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Infections and infestations Oral candidiasis	0.00% 0/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Infections and infestations Oral herpes	3.1% 1/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Infections and infestations Sinusitis	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Infections and infestations Upper respiratory tract infection	15.6% 5/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Infections and infestations Urinary tract infection	0.00% 0/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	9.1% 3/33 • From first dose of study drug up to week 12.
Infections and infestations Viral infection	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	3.1% 1/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/32 • From first dose of study drug up to week 12.	9.7% 3/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Musculoskeletal and connective tissue disorders Back pain	12.5% 4/32 • From first dose of study drug up to week 12.	9.7% 3/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Nervous system disorders Dysgeusia	3.1% 1/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	9.4% 3/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Nervous system disorders Headache	15.6% 5/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Psychiatric disorders Insomnia	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	12.5% 4/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Renal and urinary disorders Proteinuria	0.00% 0/32 • From first dose of study drug up to week 12.	6.5% 2/31 • From first dose of study drug up to week 12.	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	3.0% 1/33 • From first dose of study drug up to week 12.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.1% 1/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	9.1% 3/33 • From first dose of study drug up to week 12.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/32 • From first dose of study drug up to week 12.	0.00% 0/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	6.1% 2/33 • From first dose of study drug up to week 12.
Skin and subcutaneous tissue disorders Rash	3.1% 1/32 • From first dose of study drug up to week 12.	3.2% 1/31 • From first dose of study drug up to week 12.	6.2% 2/32 • From first dose of study drug up to week 12.	0.00% 0/33 • From first dose of study drug up to week 12.