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)

Atherosclerosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01258907
• Other study ID #: LDL4758g
• Secondary ID: GC01314
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2010
• Last updated: November 1, 2016
• Start date: March 2010

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	BioInvent International AB

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in TBR as measured by FDG-PET/CT		Baseline to Week 12	No
Secondary	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	No
Secondary	Effects of MLDL1278A on inflammatory and metabolic biomarkers		Throughout study or until early discontinuation	No