Clinical trial NCT02007252: ACZ885 for the Treatment of Abdominal Aortic Aneurysm
Official title: A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study of Subcutaneous ACZ885 for the Treatment of Abdominal Aortic Aneurysm
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Abdominal Aortic Aneurysm (AAA)
Keywords: Abdominal Aortic Aneurysm
AAA
IL-1b
Abdominal ultrasound
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-12-10
Enrollment: 65
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Primary outcomes:
measure: Change From Baseline in Abdominal Aortic Aneurysm (AAA) Size Per Year
timeFrame: month 3, month 12
Secondary outcomes:
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Kolding
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Eindhoven
country: Netherlands
facility: Novartis Investigative Site
city: Orebro
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: