A Study to Evaluate the Safety, Tolerability, and Activity of Intravenous MLDL1278A in Patients on Standard-of-Care Therapy for Stable Atherosclerotic Cardiovascular Disease (GLACIER)

• Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLDL1278A [ Time Frame: Throughout study or until early discontinuation ] [ Designated as safety issue: No ]
• Effects of MLDL1278A on inflammatory and metabolic biomarkers [ Time Frame: Throughout study or until early discontinuation ] [ Designated as safety issue: No ]

This is a Phase II (proof-of-activity), double-blind, placebo-controlled, randomized, multicenter study of MLDL1278A (also known as BI-204) involving patients on standard-of-care therapy for atherosclerotic cardiovascular disease with evidence of vascular inflammation, as quantified by FDG-PET/CT.

• Drug: MLDL1278A
  Single intravenous dose
• Drug: MLDL1278A
  Repeating intravenous dose
• Drug: placebo
  Repeating intravenous dose
• Drug: statin, stable dose
  Repeating oral dose

• Experimental: A
  Interventions:

  • Drug: MLDL1278A
  • Drug: statin, stable dose
• Experimental: B
  Interventions:

  • Drug: MLDL1278A
  • Drug: statin, stable dose
• Placebo Comparator: C
  Interventions:

  • Drug: placebo
  • Drug: statin, stable dose

Inclusion Criteria:

• Evidence of qualifying vessel (carotid or aortic) plaque inflammation
• Documented atherosclerotic vascular disease clinically stable for at least 3 months prior to screening or type 2 diabetes mellitus with elevated cardiovascular risk
• Use of a stable dose of statin therapy for at least 6 weeks prior to screening. Patients must be capable of maintaining statin therapy at a current dose level from screening until the last follow-up visit.
• For patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin-receptor blockers (ARBs), non-statin lipid-modifying therapy, thiazolidinediones, inhaled steroids, or leukotriene modifying agents, use of a stable dose for at least 6 weeks prior to screening and capable of continuing with that dose for the duration of the study

Exclusion Criteria:

• Occurrence of a cardiovascular event < 6 months prior to screening
• Pregnant, planning to become pregnant during the study, or breastfeeding
• Clinically significant abnormal laboratory values or abnormal ECG or vital signs
• History of anaphylactic reactions
• Newly discovered Type 2 diabetes mellitus (T2DM) (prior to study entry) or medical treatment for T2DM started < 3 months prior to study entry
• Use of insulin, corticosteroids (oral, rectal, or injectable), or other immunosuppressive medications
• Current or recent (within 4 weeks prior to screening) infection, including signs, symptoms or serology of any infection, including HIV, hepatitis B or C
• Impaired renal function
• History of malignancy within 2 years prior to screening
• Current life-threatening condition other than vascular disease that may prevent a patient from completing the study
• Use of an investigational drug or biologic within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study medication
• Exposure to substantial radiation within 12 months prior to screening