Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4 (GAUSS-4)

Amgen

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02634580

20140234

Details and patient eligibility

About

The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin.

Full description

After screening participants who met all inclusion/exclusion criteria were randomized with an allocation ratio of 2:2:1:1 into 4 groups: evolocumab (AMG 145) 420 mg administered by subcutaneous injection monthly and placebo pill daily; evolocumab 140 mg administered by subcutaneous injection every two weeks and placebo pill by mouth daily; placebo 420 mg administered by subcutaneous injection monthly and ezetimibe 10 mg pill daily; placebo 140 mg administered subcutaneous injection every two weeks and ezetimibe 10 mg pill daily. Randomization was stratified by screening LDL-C level and baseline statin use. Participants on low or atypical statin dose therapy must have been on a stable dose for at least 4 weeks prior to screening and throughout the blinded portion of the study; the dose could not be adjusted during screening and for the duration of the study. After Week 12, ezetimibe was discontinued and participants moved to an open-label dose of evolocumab administered by subcutaneous injection either every two weeks or monthly and their standard of care.

Enrollment: 61 patients

Sex: All

Ages: 20 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female ≥ 20 to ≤ 80 years of age
• Japanese by self-identification
• Not on a statin or on a low dose statin with stable dose for at least 4 weeks.
• Subject not at LDL-C goal
• History of statin intolerance to at least 2 statins
• Lipid lowering therapy has been stable prior to screening for at least 4 weeks
• Fasting triglycerides ≤ 400 mg/dL

Exclusion criteria

• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• 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

---

61 participants in 4 patient groups

Ezetimibe (Q2W)

Active Comparator group

Description:

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.

Treatment:

Drug: Ezetimibe

Biological: Evolocumab

Drug: 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 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.

Treatment:

Drug: Ezetimibe

Biological: Evolocumab

Drug: 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 12 weeks. From week 12 participants received open-label evolocumab 140 mg subcutaneously once every 2 weeks until week 48.

Treatment:

Biological: Evolocumab

Drug: Placebo Ezetimibe

Evolocumab QM

Experimental group

Description:

Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for 12 weeks. From week 12 participants received open-label evolocumab 420 mg subcutaneously once a month until week 48.

Treatment:

Biological: Evolocumab

Drug: Placebo Ezetimibe