ACZ885 for the Treatment of Abdominal Aortic Aneurysm
Condition: Abdominal Aortic Aneurysm (AAA)
MeSH terms: Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal
Intervention: ACZ885; Placebo
Intervention description: ACZ885 150 mg liquid pre-filled syringes were administered s.c..; Matching placebo liquid pre-filled syringes were administered s.c..
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Abdominal Aortic Aneurysm; AAA; IL-1b; Abdominal ultrasound

Summary:

      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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Male and female subjects age ≥45 years of age

          2. Infrarenal abdominal aortic aneurysm with maximum diameter: for men ≥40mm and ≤50mm;
             for women ≥38mm and ≤48mm.

          3. On a stable medical regimen for at least 2 weeks prior to dosing, per investigator
             assessment.

          4. Have an evaluable ultrasound image at screening for the quantitative determination of
             the AAA size, per imaging core lab assessment.

          5. 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:

          1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives
             of enrollment.

          2. Known diabetes by medical history, an HbA1c of ≥6.5% at screening, or on an active
             diabetic medical regimen.

          3. History of malignancy of any organ system other than localized basal cell carcinoma of
             the skin, treated or untreated, within the past 5 years.

          4. 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.

          5. 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.

          6. 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.

          7. Presence of a non-healing wound or infection, including active urinary tract
             infections, or any recent process requiring significant tissue healing per
             investigator assessment.

          8. Significant illness which has not resolved within four (4) weeks prior to initial
             dosing or with a life expectancy less than 2 years.

          9. 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.

         10. Previous infra-renal aortic surgery

         11. Planned major surgery

         12. Known aortic dissection

         13. 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.

         14. Subjects should exhibit no signs of clinically concerning unstable acceleration of AAA
             size or growth rate at the time of enrollment per investigator assessment.

         15. Known or suspected inherited connective tissue disorders (e.g., Marfan or Vascular
             Ehlers Danlos syndrome).

         16. 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).

         17. Uncontrolled or refractory hypertension per Investigator determination.

         18. Live vaccinations within 3 months prior to randomization, or live vaccinations planned
             during the study.

         19. History of untreated tuberculosis infection or evidence of active tuberculosis (TB)
             infection.

         20. History of multiple and recurring allergies or allergy to the investigational
             compound/compound class being used in this study.

         21. History of immunodeficiency diseases, including a positive HIV (ELISA and Western
             blot) test result.

         22. A positive Hepatitis B surface antigen or Hepatitis C test result whether at screening
             or historically.

         23. 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.

         24. Underlying immune disorders, autoimmunity or immunodeficiency.

         25. History of drug or alcohol abuse within the 12 months prior to dosing.