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)

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Double Blind, Placebo-Controlled Phase II Study to Evaluate the Safety, Tolerability, and Activity of Intravenous MLDL1278A in Patients on Standard-of-Care Therapy for Stable Atherosclerotic Cardiovascular Disease (GLACIER - Goal of Oxidized Ldl and Activated Macrophage Inhibition by Exposure to a Recombinant Antibody)

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: MLDL1278A
* Drug: MLDL1278A
* Drug: placebo
* Drug: statin, stable dose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: MLDL1278A<br>* Single intravenous dose<br>Drug: statin, stable dose<br>* Repeating oral dose<br>|
| Experimental: B<br> | Drug: MLDL1278A<br>* Repeating intravenous dose<br>Drug: statin, stable dose<br>* Repeating oral dose<br>|
| Placebo Comparator: C<br> | Drug: placebo<br>* Repeating intravenous dose<br>Drug: statin, stable dose<br>* Repeating oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TBR as measured by FDG-PET/CT |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLDL1278A |  | Throughout study or until early discontinuation | 
| Effects of MLDL1278A on inflammatory and metabolic biomarkers |  | Throughout study or until early discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BI-204