Brodalumab (AMG 827) in Adults With Moderate to Severe Crohn's Disease
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| ClinicalTrials.gov Identifier: NCT01150890 |
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Recruitment Status :
Terminated
(The study was terminated early based on an imbalance in worsening Crohn's disease in active treatment groups)
First Posted : June 25, 2010
Results First Posted : January 3, 2022
Last Update Posted : January 3, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Crohn's Disease | Biological: Brodalumab Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| 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 : | November 9, 2010 |
| Actual Primary Completion Date : | October 15, 2011 |
| Actual Study Completion Date : | October 15, 2011 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Participants received placebo intravenously at baseline and week 4.
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Drug: Placebo
Administered as as an intravenous (IV) infusion over at least 30 minutes. |
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Experimental: Brodalumab 210 mg
Participants received 210 mg brodalumab intravenously at baseline and week 4.
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Biological: Brodalumab
Administered as as an intravenous (IV) infusion over at least 30 minutes.
Other Name: AMG 827 |
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Experimental: Brodalumab 350 mg
Participants received 350 mg brodalumab intravenously at baseline and week 4.
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Biological: Brodalumab
Administered as as an intravenous (IV) infusion over at least 30 minutes.
Other Name: AMG 827 |
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Experimental: Brodalumab 700 mg
Participants received 700 mg brodalumab intravenously at baseline and week 4.
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Biological: Brodalumab
Administered as as an intravenous (IV) infusion over at least 30 minutes.
Other Name: AMG 827 |
- Percentage of Participants Who Achieved Clinical Remission at Week 6 [ Time Frame: 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.
- Percentage of Participants Who Achieved a CDAI Response at Week 6 [ Time Frame: 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.
- Change From Baseline in CDAI at Week 6 [ Time Frame: 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) [ Time Frame: 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 [ 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. ]
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 [ 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. ]
An optional pharmacokinetic (PK) substudy was offered to participants at a subset of sites and required additional informed consent.
Serum concentrations of brodalumab were measured using a validated analytical method, enzyme-linked immusosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay was 0.0500 μg/mL.
- Area Under the Serum Concentration Versus Time Curve, From Time Zero to the Last Measurable Concentration (AUClast) for Brodalumab [ 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. ]
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 [ 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. ]
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.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01150890
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| Study Director: | MD | Amgen |
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT01150890 |
| Other Study ID Numbers: |
20090072 2010-019544-39 ( EudraCT Number ) |
| First Posted: | June 25, 2010 Key Record Dates |
| Results First Posted: | January 3, 2022 |
| Last Update Posted: | January 3, 2022 |
| Last Verified: | November 2021 |
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Ileal Crohn's Disease Ileo-colonic Crohn's Disease Colonic Chron's Disease |
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Crohn Disease Inflammatory Bowel Diseases Gastroenteritis Gastrointestinal Diseases |
Digestive System Diseases Intestinal Diseases Brodalumab Dermatologic Agents |