Crohn's Disease
Conditions
Keywords
Ileal Crohn's Disease, Ileo-colonic Crohn's Disease, Colonic Chron's Disease
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.
Interventions
BIOLOGICALBrodalumab
Administered as as an intravenous (IV) infusion over at least 30 minutes.
DRUGPlacebo
Administered as as an intravenous (IV) infusion over at least 30 minutes.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Australia, Belgium, Canada, France, Netherlands, Poland, Spain, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo intravenously at baseline and week 4. | 32 |
| Brodalumab 210 mg Participants received 210 mg brodalumab intravenously at baseline and week 4. | 32 |
| Brodalumab 350 mg Participants received 350 mg brodalumab intravenously at baseline and week 4. | 33 |
| Brodalumab 700 mg Participants received 700 mg brodalumab intravenously at baseline and week 4. | 33 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative Decision | 4 | 4 | 5 | 6 |
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Disease progression | 0 | 7 | 3 | 7 |
| Overall Study | Ineligibility determined | 0 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 2 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Brodalumab 210 mg | Brodalumab 350 mg | Brodalumab 700 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 13 | 32.8 years STANDARD_DEVIATION 10.2 | 36.8 years STANDARD_DEVIATION 12.6 | 36.7 years STANDARD_DEVIATION 10 | 35.8 years STANDARD_DEVIATION 11.5 |
| Crohn's Disease Activity Index (CDAI) | 327.7 score on a scale STANDARD_DEVIATION 63 | 333.2 score on a scale STANDARD_DEVIATION 61.9 | 334.5 score on a scale STANDARD_DEVIATION 60.3 | 315.4 score on a scale STANDARD_DEVIATION 54 | 327.5 score on a scale STANDARD_DEVIATION 59.6 |
| Duration of Crohn's Disease | 11.38 years STANDARD_DEVIATION 9.35 | 9.57 years STANDARD_DEVIATION 7.64 | 14.21 years STANDARD_DEVIATION 10.35 | 11.71 years STANDARD_DEVIATION 7.36 | 11.75 years STANDARD_DEVIATION 8.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 26 Participants | 26 Participants | 27 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 6 Participants | 6 Participants | 5 Participants | 24 Participants |
| Predominant Location of Crohn's Disease (CD) Involvement Colonic | 8 Participants | 7 Participants | 11 Participants | 13 Participants | 39 Participants |
| Predominant Location of Crohn's Disease (CD) Involvement Ileal | 6 Participants | 5 Participants | 4 Participants | 3 Participants | 18 Participants |
| Predominant Location of Crohn's Disease (CD) Involvement Ileo-colonic | 17 Participants | 19 Participants | 17 Participants | 16 Participants | 69 Participants |
| Predominant Location of Crohn's Disease (CD) Involvement Missing | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Predominant Location of Crohn's Disease (CD) Involvement Unknown | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 7 Participants | 6 Participants | 6 Participants | 5 Participants | 24 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 23 Participants | 26 Participants | 27 Participants | 100 Participants |
| Sex: Female, Male Female | 17 Participants | 19 Participants | 21 Participants | 21 Participants | 78 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 12 Participants | 12 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 32 | 21 / 31 | 23 / 32 | 20 / 33 |
| serious Total, serious adverse events | 2 / 32 | 3 / 31 | 8 / 32 | 9 / 33 |
Outcome results
Primary
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.
Time frame: Week 6
Population: The full analysis set included all randomized participants; missing data were analyzed using the non-responder imputation method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Remission at Week 6 | 3.1 percentage of participants |
| Brodalumab 210 mg | Percentage of Participants Who Achieved Clinical Remission at Week 6 | 3.1 percentage of participants |
| Brodalumab 350 mg | Percentage of Participants Who Achieved Clinical Remission at Week 6 | 15.2 percentage of participants |
| Brodalumab 700 mg | Percentage of Participants Who Achieved Clinical Remission at Week 6 | 9.1 percentage of participants |
Comparison: 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.p-value: 0.1941Overall Trend test
p-value: 195% CI: [-0.09, 0.09]Chi-squared
p-value: 0.096695% CI: [-0.02, 0.26]Chi-squared
p-value: 0.320895% CI: [-0.06, 0.17]Chi-squared
Secondary
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.
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.
Population: The PK analysis set with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Brodalumab 210 mg | Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab | After second dose | 595 day*μg/mL | Standard Deviation 268 |
| Brodalumab 210 mg | Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab | After first dose | 501 day*μg/mL | Standard Deviation 190 |
| Brodalumab 350 mg | Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab | After first dose | 1432 day*μg/mL | Standard Deviation 714 |
| Brodalumab 350 mg | Area Under the Serum Concentration Versus Time Curve From Time Zero to 28 Days (AUC0-28) for Brodalumab | After second dose | 1434 day*μg/mL | Standard Deviation 597 |
Secondary
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.
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.
Population: The PK analysis set with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Brodalumab 210 mg | Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab | After first dose | 501 day*μg/mL | Standard Deviation 190 |
| Brodalumab 210 mg | Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab | After second dose | 622 day*μg/mL | Standard Deviation 330 |
| Brodalumab 350 mg | Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab | After first dose | 1428 day*μg/mL | Standard Deviation 715 |
| Brodalumab 350 mg | Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab | After second dose | 1558 day*μg/mL | Standard Deviation 691 |
Secondary
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.
Time frame: Baseline and week 6
Population: Full analysis set; missing CDAI scores were imputed using baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDAI at Week 6 | -28.2 score on a scale | Standard Deviation 86 |
| Brodalumab 210 mg | Change From Baseline in CDAI at Week 6 | -8.7 score on a scale | Standard Deviation 95.3 |
| Brodalumab 350 mg | Change From Baseline in CDAI at Week 6 | -35.4 score on a scale | Standard Deviation 105.6 |
| Brodalumab 700 mg | Change From Baseline in CDAI at Week 6 | -0.6 score on a scale | Standard Deviation 105.9 |
p-value: 0.4161ANCOVA
p-value: 0.8094ANCOVA
p-value: 0.304ANCOVA
Secondary
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.
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.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of Brodalumab | After first dose | 53.1 μg/mL | Standard Deviation 6.4 |
| Placebo | Maximum Observed Concentration (Cmax) of Brodalumab | After second dose | 54.5 μg/mL | Standard Deviation 1.08 |
| Brodalumab 210 mg | Maximum Observed Concentration (Cmax) of Brodalumab | After first dose | 96.4 μg/mL | Standard Deviation 17.6 |
| Brodalumab 210 mg | Maximum Observed Concentration (Cmax) of Brodalumab | After second dose | 98.7 μg/mL | Standard Deviation 20.6 |
| Brodalumab 350 mg | Maximum Observed Concentration (Cmax) of Brodalumab | After first dose | 184 μg/mL | Standard Deviation 64.9 |
| Brodalumab 350 mg | Maximum Observed Concentration (Cmax) of Brodalumab | After second dose | 171 μg/mL | Standard Deviation 63.2 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation of study drug | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation from study | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related fatal adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events (TRTEAE) | 10 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All treatment emergent adverse events (TEAEs) | 25 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation of study drug | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation from study | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 2 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 3 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation from study | 4 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation from study | 2 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation of study drug | 3 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation of study drug | 2 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events (TRTEAE) | 13 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related fatal adverse events | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 3 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All treatment emergent adverse events (TEAEs) | 23 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation of study drug | 2 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All treatment emergent adverse events (TEAEs) | 27 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events (TRTEAE) | 21 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related fatal adverse events | 0 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation from study | 2 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 8 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 0 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation of study drug | 3 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation from study | 3 Participants |
| Brodalumab 350 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 4 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation of study drug | 3 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 0 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All treatment emergent adverse events (TEAEs) | 28 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 9 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 5 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation from study | 0 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related fatal adverse events | 0 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TRTEAE leading to discontinuation of study drug | 0 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events (TRTEAE) | 14 Participants |
| Brodalumab 700 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs leading to discontinuation from study | 3 Participants |
Secondary
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.
Time frame: Week 6
Population: Full analysis set; non-responder imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a CDAI Response at Week 6 | 12.5 percentage of participants |
| Brodalumab 210 mg | Percentage of Participants Who Achieved a CDAI Response at Week 6 | 16.1 percentage of participants |
| Brodalumab 350 mg | Percentage of Participants Who Achieved a CDAI Response at Week 6 | 27.3 percentage of participants |
| Brodalumab 700 mg | Percentage of Participants Who Achieved a CDAI Response at Week 6 | 15.2 percentage of participants |
p-value: 0.683195% CI: [-0.14, 0.21]Chi-squared
p-value: 0.139695% CI: [-0.04, 0.34]Chi-squared
p-value: 0.758895% CI: [-0.14, 0.19]Chi-squared
Secondary
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.
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.
Population: The PK analysis set with available data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After second dose | 0.031 days |
| Placebo | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After first dose | 0.034 days |
| Brodalumab 210 mg | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After second dose | 0.033 days |
| Brodalumab 210 mg | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After first dose | 0.034 days |
| Brodalumab 350 mg | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After second dose | 0.029 days |
| Brodalumab 350 mg | Time to Maximum Observed Concentration (Tmax) of Brodalumab | After first dose | 0.036 days |