ACZ885 for the Treatment of Abdominal Aortic Aneurysm

Study Overview
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Brief Summary
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This study was designed to assess the safety, tolerability and efficacy of ACZ885 on aneurysmal growth rate in subjects with abdominal aortic aneurysms (AAA). The purpose of the study was to provide data to enable decisions regarding the further development of ACZ885 for subjects with abdominal aortic aneurysms. The design of this study addressed the primary objective of evaluating the change in aneurysmal size in subjects with AAA as a result of treatment with ACZ885.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study of Subcutaneous ACZ885 for the Treatment of Abdominal Aortic Aneurysm

Conditions
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Abdominal Aortic Aneurysm (AAA)

Intervention / Treatment
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* Drug: ACZ885
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female subjects age ≥45 years of age Infrarenal abdominal aortic aneurysm with maximum diameter: for men ≥40mm and ≤50mm; for women ≥38mm and ≤48mm. On a stable medical regimen for at least 2 weeks prior to dosing, per investigator assessment. Have an evaluable ultrasound image at screening for the quantitative determination of the AAA size, per imaging core lab assessment. At screening, vital signs should be within the following ranges: (a) oral body temperature between 35.0-37.5°C; (b) systolic blood pressure, 90-170 mm Hg; (c) diastolic blood pressure, 50-100 mm Hg; (d) pulse rate, 40 - 100 bpm. Key Exclusion Criteria: Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment. Known diabetes by medical history, an HbA1c of ≥6.5% at screening, or on an active diabetic medical regimen. History of malignancy of any organ system other than localized basal cell carcinoma of the skin, treated or untreated, within the past 5 years. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing and 30-day follow up period of the study. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. Subjects on the following medications: (a) Chronic systemic steroid treatment or other systemic immunosuppression; (b) Any biologic drugs targeting the immune system, along with a history of any previous use of such drugs. Presence of a non-healing wound or infection, including active urinary tract infections, or any recent process requiring significant tissue healing per investigator assessment. Significant illness which has not resolved within four (4) weeks prior to initial dosing or with a life expectancy less than 2 years. Any of the following concomitant hepatic or renal conditions or diseases: (a) Nephrotic syndrome, or eGFR less than 30 mL/min/1.73 m2 per CRCL formula; (b) Prior organ transplant requiring immunosuppressive therapy; (c) Known active or recurrent hepatic disorder. Previous infra-renal aortic surgery Planned major surgery Known aortic dissection Subjects with eligible AAA diameter, but with known slow growth (<2mm/year) or known stable AAA size over the prior one year of surveillance per investigator assessment. Subjects should exhibit no signs of clinically concerning unstable acceleration of AAA size or growth rate at the time of enrollment per investigator assessment. Known or suspected inherited connective tissue disorders (e.g., Marfan or Vascular Ehlers Danlos syndrome). Recently unstable clinically significant cardiac disease within 3 months of screening, including but not limited to, unstable angina, acute myocardial infarction, and congestive heart failure (NYHA class IV). Uncontrolled or refractory hypertension per Investigator determination. Live vaccinations within 3 months prior to randomization, or live vaccinations planned during the study. History of untreated tuberculosis infection or evidence of active tuberculosis (TB) infection. History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. A positive Hepatitis B surface antigen or Hepatitis C test result whether at screening or historically. For USA sites utilizing CT angiograms, subjects with a history of a previous reaction to contrast agent, a known sensitivity to iodine and known allergies (e.g, shellfish allergy), or other hypersensitivities to contrast agents. Underlying immune disorders, autoimmunity or immunodeficiency. History of drug or alcohol abuse within the 12 months prior to dosing.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACZ885<br>Participants received ACZ885 150 mg subcutaneously (s.c.) once per month for 12 months. | Drug: ACZ885<br>* ACZ885 150 mg liquid pre-filled syringes were administered s.c..<br>|
| Placebo Comparator: Placebo<br>Participants received matching placebo to ACZ885 s.c. once per month for 12 months. | Drug: Placebo<br>* Matching placebo liquid pre-filled syringes were administered s.c..<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abdominal Aortic Aneurysm (AAA) Size Per Year | Size of the AAA was determined using an abdominal ultrasound technique at baseline, 3 months, and 12 months after treatment with study drug. Growth rate (in mm/year) was calculated from the change in AAA size compared to baseline | month 3, month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abdominal Aortic Aneurysm, AAA, IL-1b, Abdominal ultrasound