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)

Phase 2

Completed

• Conditions: Atherosclerosis
• Interventions: Drug: MLDL1278A; Drug: placebo; Drug: statin, stable dose

• Registration Number: NCT01258907
• Lead Sponsor: Genentech, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-12-10
• Study First Submitted QC: 2010-12-10
• Study First Posted: 2010-12-13
• Primary Completion: 2012-07
• Disposition First Submitted: 2013-08-20
• Disposition First Submitted QC: 2013-08-20
• Disposition First Posted: 2013-08-28
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 147

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	statin, stable dose	-
B	MLDL1278A	-
B	statin, stable dose	-
C	statin, stable dose	-
A	MLDL1278A	-
C	placebo	-

Primary Outcome Measures

Name	Time	Method
Change in TBR as measured by FDG-PET/CT	Baseline to Week 12

Secondary Outcome Measures

Name	Time	Method
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