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)

Genentech

Status and phase: Completed; Phase 2

Conditions: Atherosclerosis

Treatments: Drug: placebo; Drug: statin, stable dose; Drug: MLDL1278A

Study type: Interventional

Funder types: Industry

Identifiers

NCT01258907

LDL4758g

GC01314 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 147 patients

Sex: All

Ages: 35 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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147 participants in 3 patient groups, including a placebo group

A

Experimental group

Treatment:

Drug: statin, stable dose

Drug: MLDL1278A

Drug: MLDL1278A

B

Experimental group

Treatment:

Drug: statin, stable dose

Drug: MLDL1278A

Drug: MLDL1278A

C

Placebo Comparator group

Treatment:

Drug: statin, stable dose

Drug: placebo