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)

NCT01258907 | Completed Phase 2

• 2 other identifiers: LDL4758gGC01314
• Study Type: interventional
• Target: 147
• Locations: 2 countries
• Sites: 24

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.

Conditions

Atherosclerosis

Keywords

BI-204

Outcome Measures

Primary Outcomes (1)

• Change in TBR as measured by FDG-PET/CT

  Baseline to Week 12

Secondary Outcomes (2)

• 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

Study Arms (3)

A

EXPERIMENTAL

Drug: MLDL1278A; Drug: statin, stable dose

B

EXPERIMENTAL

Drug: MLDL1278A; Drug: statin, stable dose

C

PLACEBO COMPARATOR

Drug: placebo; Drug: statin, stable dose

Interventions

MLDL1278A DRUG

Single intravenous dose

A

placebo DRUG

Repeating intravenous dose

C

statin, stable dose DRUG

Repeating oral dose

A; B; C

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• BioInvent International AB: collaborator

Study Sites (24)

Unknown Facility

Torrance, California, 90502, United States

Location

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Colorado Springs, Colorado, 80904, United States

Location

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Washington D.C., District of Columbia, 20010, United States

Location

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Gainesville, Florida, 32605, United States

Location

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Jacksonville, Florida, 32216, United States

Location

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Indianapolis, Indiana, 46260, United States

Location

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Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Haverhill, Massachusetts, 01830, United States

Location

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Royal Oak, Michigan, 48073, United States

Location

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Minneapolis, Minnesota, 55455, United States

Location

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Saint Paul, Minnesota, 55102, United States

Location

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Kansas City, Missouri, 64111, United States

Location

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Newington, New Hampshire, 03801, United States

Location

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New York, New York, 10001, United States

Location

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New York, New York, 10029, United States

Location

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North Massapequa, New York, 11758, United States

Location

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Cincinnati, Ohio, 45219, United States

Location

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Cincinnati, Ohio, 45227, United States

Location

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Portland, Oregon, 97225-3411, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

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Houston, Texas, 77002, United States

Location

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Houston, Texas, 77030, United States

Location

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Ottawa, Ontario, K1Y 4W7, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 1C8, Canada

Location

MeSH Terms

Conditions

Atherosclerosis

Interventions

MLDL1278A; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Joshua Lehrer-Graiwer, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: March 1, 2010
• Primary Completion: July 1, 2012
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

CA (2); US (22)