Clinical trial NCT01199302: Long-term Safety Study of Brodalumab in Adults With Crohn's Disease
Official title: A Long-term Assessment of Safety and Efficacy of AMG 827 Treatment in Subjects With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Amgen
Crohn's
Inflammatory Bowel Disease
IBD
Irritable Bowel Syndrome
IBS
Inflammation
bowel
colon
gastrointestinal
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-09-10
Enrollment: 67
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of long-term treatment with brodalumab in adults with Crohn's disease.

Detailed description: This study is an open-label extension of study 20090072 (NCT01150890) in adults with Crohn's disease.

Eligibility criteria: Inclusion Criteria:

* Subject was randomized into study 20090072 (NCT01150890) and completed the week 12 evaluation.
* Subject completed the week 12 evaluation in study 20090072 no more than 1 year prior to the planned first visit of AMG 827 in 20100008.
* Subject or subject's legally acceptable representative has provided informed consent.
* Subject meets regional recommendations for immunizations, eg, United States Centers for Disease Control and Prevention recommendations for subjects enrolled in the United States.
* For subjects with ≥ 3 months between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008: If testing is clinically indicated in the opinion of the investigator (eg, because of known recent exposure), then subject has negative test for hepatitis B, hepatitis C, and/or human immunodeficiency virus (HIV).
* For female subjects with ≤ 4 weeks between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008: Subject has a negative urine pregnancy test at baseline prior to the first dose of AMG 827 in the open-label extension (except those at least 2 years post menopausal or surgically sterile).
* For female subjects with \> 4 weeks between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008: Subject has a negative serum pregnancy test within 28 days before initiating AMG 827 and a negative urine pregnancy test at baseline prior to the first dose of AMG 827 in the open-label extension (except those at least 2 years post menopausal or surgically sterile).
* For subjects with ≥ 3 months between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008, if clinically indicated in the opinion of the investigator (eg, because of known recent exposure) please assess the following:
* If the subject entered 20090072 with a negative purified protein derivative (PPD) test: Subject must have a negative PPD test within 30 days prior to the planned first dose of AMG 827. Tuberculin skin tests should be considered positive when they have greater than or equal to 5 mm of induration at 48-72 hours after test is placed.
* If the subject entered 20090072 with a positive PPD: Subject must have a negative Quantiferon test within 30 days prior to the planned first dose of AMG 827.

Exclusion Criteria:

* Subject had any serious adverse event reported during study 20090072 and considered to be related to investigational product.
* Subject experienced an adverse event or laboratory abnormality in study 20090072 that, in the opinion of the investigator, could cause extension of treatment to be detrimental to the subject, prevent the subject from completing the study, or interfere with the interpretation of the study results.
* Subject has known sensitivity to any of the products to be administered during dosing.

Other medical conditions

* Subject is currently experiencing an infection of Common Terminology Criteria for Adverse Events grade 2 (if requiring oral medication) or higher. Subject is ineligible until the infection resolves.
* Subject has a serious infection, defined as requiring hospitalization or intravenous antibiotics, within 8 weeks before the first dose of AMG 827 in 20100008.
* For subjects with ≥ 3 months between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008: Subject has recurrent or chronic infections, defined as ≥ 3 infections requiring anti-microbials over the past 12 months prior to screening.
* Subject has a significant concurrent medical condition, including
* Type 1 diabetes
* Uncontrolled type 2 diabetes
* Moderate to severe heart failure (New York Heart Association class III or IV)
* Myocardial infarction within the last year
* Current or history of unstable angina pectoris within the last year
* Uncontrolled hypertension as defined by resting blood pressure ≥ 150/90 mmHg prior to first investigational product dose (confirmed by a repeat assessment)
* Severe chronic pulmonary disease (eg, requiring oxygen therapy)
* Major chronic inflammatory disease or connective tissue disease other than Crohn's disease (eg, systemic lupus erythematosus, rheumatoid arthritis, psoriasis)
* Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma
* History of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin).
* Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject
* Laboratory abnormalities
* For subjects with \> 4 weeks between the week 12 visit of 20090072 and the planned first dose of AMG 827 in 20100008, subject has laboratory abnormalities at screening, including
* Elevated aspartate aminotransferase or alanine aminotransferase (\> 2x upper limit of normal)
* Serum direct bilirubin ≥ 1.5x upper limit of normal
* Hemoglobin \< 10 g/dL
* Hemoglobin A1c \> 8.0 (for subjects with type 2 diabetes)
* Platelet count \< 125,000 /mm\^3
* White blood cell count \< 3,000 cells/mm\^3
* Absolute neutrophil count \< 2,000/mm\^3
* Creatinine clearance \< 50 mL/min (Cockroft-Gault formula, central lab will calculate value and provide to sites)
* Any other laboratory abnormality, which, in the opinion of the investigator, could cause extension of treatment to be detrimental to the subject, prevent the subject from completing the study, or interfere with the interpretation of the study results
* Washouts and non-permitted drugs
* Subject has used Tysabri (natalizumab) subsequent to study 20090072.
* Subject received an anti-tumor necrosis factor agent within 8 weeks prior to the first dose of AMG 827 in 20100008.
* Subject received other commercially available biologic agent (eg, ustekinumab) within 12 weeks prior to the first dose of AMG 827 in 20100008.
* Subject received an investigational agent (other than AMG 827), investigational procedure, or participated in an investigational device study subsequent to study 20090072.
* Subject received live vaccines within 12 weeks prior to the first dose of AMG 827 in 20100008.
* Subject received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus within 4 weeks prior to the first dose of AMG 827 in 20100008.
* General or other
* Female subject is not willing to use highly effective contraception during treatment with AMG 827 (except if at least 2 years postmenopausal or surgically sterile).
* Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study.
* Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
* Subject will not be available for protocol required study visits, to the best of the subject and investigator's knowledge.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug until the end of study; median (min, max) duration was 70 days (14, 223)
measure: Percentage of Participants Who Achieved a CDAI Response
timeFrame: Baseline of the parent study and weeks 2, 4, 6, 8, 10, 12, 16, and 20
measure: Percentage of Participants Who Achieved Clinical Remission
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 16, and 20
Secondary outcomes:
measure: CDAI Score Over Time
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 16, and 20
measure: Change From Baseline in CDAI Score Over Time
timeFrame: Baseline of the parent study and Weeks 2, 4, 6, 8, 10, 12, 16, and 20
measure: Number of Participants Who Developed Anti-brodalumab Binding Antibodies
timeFrame: Blood samples were collected at study entry, week 4, 24 and at last visit (maximum time on study was 32 weeks).
measure: Change From Baseline in C-reactive Protein (CRP) Levels Over Time
timeFrame: Baseline of the parent study and Weeks 2, 4, 6, 8, 10, 12, 16, and 20
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Hammond
country: United States
facility: Research Site
state: Louisiana
city: Chevy Chase
country: United States
facility: Research Site
state: Maryland
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Mexico
country: United States
facility: Research Site
state: Missouri
city: Great Neck
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Kurralta Park
country: Australia
facility: Research Site
state: South Australia
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Fitzroy
country: Australia
facility: Research Site
state: Victoria
city: Fremantle
country: Australia
facility: Research Site
state: Western Australia
city: Bonheiden
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Lille cedex
country: France
facility: Research Site
city: Nice Cedex 3
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Toulouse Cedex 09
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Sopot
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Pontevedra
country: Spain
facility: Research Site
state: Galicia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: