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

Hypercholesterolemia Clinical Trial

— GAUSS-4  

Official title:

A Double-blind, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Japanese Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor Due to Muscle Related Side Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02634580
• Other study ID #: 20140234
• Status: Completed
• Phase: Phase 3
• Start date: February 27, 2016
• Est. completion date: May 26, 2018

Study information

• Verified date: October 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: May 26, 2018
• Est. primary completion date: August 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Biological:
• Evolocumab
Administered by subcutaneous injection

Drug:
• Ezetimibe
Tablet for oral administration
• Placebo to Evolocumab
Administered by subcutaneous injection
• Placebo Ezetimibe
Tablet for oral administration

Locations

Country	Name	City	State
Japan	Research Site	Bunkyo-ku	Tokyo
Japan	Research Site	Chiba-shi	Chiba
Japan	Research Site	Chikushino-shi	Fukuoka
Japan	Research Site	Chuo-ku	Tokyo
Japan	Research Site	Fujimi-shi	Saitama
Japan	Research Site	Hamamatsu-shi	Shizuoka
Japan	Research Site	Higashiyamato-shi	Tokyo
Japan	Research Site	Hiroshima-shi	Hiroshima
Japan	Research Site	Iruma-gun	Saitama
Japan	Research Site	Kagoshima-shi	Kagoshima
Japan	Research Site	Kahoku-gun	Ishikawa
Japan	Research Site	Kanazawa-shi	Ishikawa
Japan	Research Site	Kawaguchi-shi	Saitama
Japan	Research Site	Kisarazu-shi	Chiba
Japan	Research Site	Kobe-shi	Hyogo
Japan	Research Site	Koga-shi	Ibaraki
Japan	Research Site	Koga-shi	Fukuoka
Japan	Research Site	Komatsu-shi	Ishikawa
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kyoto-shi	Kyoto
Japan	Research Site	Matsudo-shi	Chiba
Japan	Research Site	Morioka-shi	Iwate
Japan	Research Site	Morioka-shi	Iwate
Japan	Research Site	Musashino-shi	Tokyo
Japan	Research Site	Nagoya-shi	Aichi
Japan	Research Site	Nagoya-shi	Aichi
Japan	Research Site	Nakagami-gun	Okinawa
Japan	Research Site	Ohsaki-shi	Miyagi
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Osaka-Shi	Osaka
Japan	Research Site	Shinagawa-ku	Tokyo
Japan	Research Site	Sukagawa-shi	Fukushima
Japan	Research Site	Sukagawa-shi	Fukushima
Japan	Research Site	Yokohama-shi	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12	For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.	Baseline and Weeks 10 and 12
Primary	Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12		Baseline and week 12
Secondary	Change From Baseline in LDL-C at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Change From Baseline in LDL-C at Week 12		Baseline and week 12
Secondary	Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL	Mean low density lipoprotein-cholesterol response was defined as LDL-C < 70 mg/dL [1.8 mol/L].	Weeks 10 and 12
Secondary	Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12		Week 12
Secondary	Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in Total Cholesterol at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12		Baseline and Weeks 10 and 12
Secondary	Percent Change From Baseline in Apolipoprotein B at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in Lipoprotein(a) at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in Triglycerides at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in HDL-C at Week 12		Baseline and week 12
Secondary	Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12		Baseline and weeks 10 and 12
Secondary	Percent Change From Baseline in VLDL-C at Week 12		Baseline and week 12

External Links

•   AmgenTrials clinical trials website