Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 (MENDEL-2)

Amgen

Status and phase: Completed; Phase 3

Conditions: Hyperlipidemia

Treatments: Biological: Placebo to Evolocumab; Other: Placebo to Ezetimibe; Drug: Ezetimibe; Biological: Evolocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01763827

20110114

Details and patient eligibility

About

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Enrollment: 615 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female ≥ 18 to ≤ 80 years of age
• National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less
• Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and <190 mg/dL
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion criteria

• History of coronary heart disease
• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)
• Uncontrolled hypothyroidism or hyperthyroidism

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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615 participants in 6 patient groups, including a placebo group

Placebo Q2W

Placebo Comparator group

Description:

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.

Treatment:

Biological: Placebo to Evolocumab

Other: Placebo to Ezetimibe

Placebo QM

Placebo Comparator group

Description:

Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

Treatment:

Biological: Placebo to Evolocumab

Other: Placebo to Ezetimibe

Ezetimibe (Q2W)

Active Comparator group

Description:

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Treatment:

Drug: Ezetimibe

Biological: Placebo to Evolocumab

Ezetimibe (QM)

Active Comparator group

Description:

Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Treatment:

Drug: Ezetimibe

Biological: Placebo to Evolocumab

Evolocumab Q2W

Experimental group

Description:

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Treatment:

Biological: Evolocumab

Other: Placebo to Ezetimibe

Evolocumab QM

Experimental group

Description:

Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Treatment:

Biological: Evolocumab

Other: Placebo to Ezetimibe