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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: MLDL1278A; Drug: MLDL1278A; Drug: statin, stable dose; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
• United States
  • California
    • Torrance, California, United States, 90502
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Gainesville, Florida, United States, 32605
    • Jacksonville, Florida, United States, 32216
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
    • Haverhill, Massachusetts, United States, 01830
  • Michigan
    • Royal Oak, Michigan, United States, 48073
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
    • Saint Paul, Minnesota, United States, 55102
  • Missouri
    • Kansas City, Missouri, United States, 64111
  • New Hampshire
    • Newington, New Hampshire, United States, 03801
  • New York
    • New York, New York, United States, 10001
    • New York, New York, United States, 10029
    • North Massapequa, New York, United States, 11758
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cincinnati, Ohio, United States, 45227
  • Oregon
    • Portland, Oregon, United States, 97239
    • Portland, Oregon, United States, 97225-3411
  • Texas
    • Houston, Texas, United States, 77030
    • Houston, Texas, United States, 77002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: C	Drug: statin, stable dose; Repeating oral dose; Drug: placebo; Repeating intravenous dose
Experimental: A	Drug: MLDL1278A; Single intravenous dose; Drug: MLDL1278A; Repeating intravenous dose; Drug: statin, stable dose; Repeating oral dose
Experimental: B	Drug: MLDL1278A; Single intravenous dose; Drug: MLDL1278A; Repeating intravenous dose; Drug: statin, stable dose; Repeating oral dose

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: BioInvent International AB
• Investigators: Study Director: Joshua Lehrer-Graiwer, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 13, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: BI-204
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: LDL4758g; GC01314 (Other Identifier: Hoffmann-La Roche)