Long-term Safety Study of Brodalumab in Adults With Crohn's Disease

Crohn's Disease Clinical Trial

Official title:

A Long-term Assessment of Safety and Efficacy of AMG 827 Treatment in Subjects With Crohn's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01199302
• Other study ID #: 20100008
• Secondary ID: 2010-020881-53
• Status: Terminated
• Phase: Phase 2
• Start date: February 2, 2011
• Est. completion date: October 18, 2011

Study information

• Verified date: November 2021
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 67
• Est. completion date: October 18, 2011
• Est. primary completion date: October 18, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• Brodalumab
Administered intravenously once every 4 weeks

Locations

Country	Name	City	State
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Fitzroy	Victoria
Australia	Research Site	Fremantle	Western Australia
Australia	Research Site	Kurralta Park	South Australia
Belgium	Research Site	Bonheiden
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Roeselare
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Winnipeg	Manitoba
France	Research Site	Lille cedex
France	Research Site	Nice Cedex 3
France	Research Site	Paris
France	Research Site	Paris Cedex 10
France	Research Site	Toulouse Cedex 09
France	Research Site	Vandoeuvre les Nancy
Netherlands	Research Site	Amsterdam
Poland	Research Site	Bydgoszcz
Poland	Research Site	Sopot
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Pontevedra	Galicia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chevy Chase	Maryland
United States	Research Site	Great Neck	New York
United States	Research Site	Hammond	Louisiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Mexico	Missouri
United States	Research Site	Nashville	Tennessee
United States	Research Site	Ogden	Utah
United States	Research Site	Rochester	Minnesota
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject including worsening of a pre-existing medical condition, and not necessarily having 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.; The investigator assessed whether each AE was possibly related to the study drug.; A serious adverse event is defined as an AE that met at least 1 of the following serious 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.	From first dose of study drug until the end of study; median (min, max) duration was 70 days (14, 223)
Primary	Percentage of Participants Who Achieved a CDAI Response	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.	Baseline of the parent study and weeks 2, 4, 6, 8, 10, 12, 16, and 20
Primary	Percentage of Participants Who Achieved Clinical Remission	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.	Weeks 2, 4, 6, 8, 10, 12, 16, and 20
Secondary	CDAI Score Over Time	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.	Weeks 2, 4, 6, 8, 10, 12, 16, and 20
Secondary	Change From Baseline in CDAI Score Over Time	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.	Baseline of the parent study and Weeks 2, 4, 6, 8, 10, 12, 16, and 20
Secondary	Number of Participants Who Developed Anti-brodalumab Binding Antibodies	Binding antibodies to brodalumab were detected using an anti-brodalumab immunoassay.	Blood samples were collected at study entry, week 4, 24 and at last visit (maximum time on study was 32 weeks).
Secondary	Change From Baseline in C-reactive Protein (CRP) Levels Over Time		Baseline of the parent study and Weeks 2, 4, 6, 8, 10, 12, 16, and 20

External Links

•   AmgenTrials clinical trials website