Safety and Efficacy of Evolocumab in Addition to Optimal Stable Background Statin Therapy in Chinese Participants With Primary Hypercholesterolemia and Mixed Dyslipidemia

NCT03433755 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 20150172
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 31

Brief Summary

This study is being done to learn more about evolocumab in Chinese people with primary hypercholesterolemia or mixed dyslipidemia. This study will see if evolocumab will reduce low density lipoprotein cholesterol (LDL-C) in Chinese people who are also taking a certain type of lipid-lowering medication (statins with or without ezetimibe) and whether it causes any side effects.

Conditions

Primary Hypercholesterolemia; Mixed Dyslipidemia

Keywords

Evolocumab; Repatha; Statin; Chinese; China; Hypercholesterolemia; Mixed Dyslipidemia; High Cholesterol; Lowering cholesterol

Outcome Measures

Primary Outcomes (2)

• Co-Primary Endpoint: Percent Change From Baseline in LDL-C: Mean of Weeks 10 and 12

  Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.

  Baseline, Weeks 10 and 12

• Co-Primary Endpoint: Percent Change From Baseline in LDL-C at Week 12

  Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit as covariates.

  Baseline, Week 12

Secondary Outcomes (20)

• Change From Baseline in LDL-C: Mean of Weeks 10 and 12

  Baseline, Weeks 10 and 12

• Change From Baseline in LDL-C at Week 12

  Baseline, Week 12

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C): Mean of Weeks 10 and 12

  Baseline, Weeks 10 and 12

• Percent Change From Baseline in Non-HDL-C at Week 12

  Baseline, Week 12

• Percent Change From Baseline in Apolipoprotein B (ApoB): Mean of Weeks 10 and 12

  Baseline, Weeks 10 and 12

Study Arms (4)

Placebo Q2W

PLACEBO COMPARATOR

Placebo subcutaneous (SC) Q2W for 12 weeks

Drug: placebo

Placebo QM

PLACEBO COMPARATOR

Placebo SC QM for 12 weeks

Drug: placebo

Evolocumab 140 mg Q2W

EXPERIMENTAL

Evolocumab 140 mg SC Q2W for 12 weeks

Drug: evolocumab

Evolocumab 420 mg QM

EXPERIMENTAL

Evolocumab 420 mg SC QM for 12 weeks

Drug: evolocumab

Interventions

evolocumab DRUG

Evolocumab will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive evolocumab (AMG 145) every 2 weeks or monthly subcutaneously.

Also known as: Repatha; AMG 145

Evolocumab 140 mg Q2W; Evolocumab 420 mg QM

placebo DRUG

Placebo will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive placebo every 2 weeks or monthly subcutaneously.

Placebo Q2W; Placebo QM

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age at signing of informed consent form
• On an approved statin, with or without ezetimibe, at optimal stable daily dose(s) for at least 4 weeks before LDL-C screening and, in the opinion of the investigator, not requiring uptitration
• Fasting LDL-C as determined by central laboratory at screening ≥ 80 mg/dL
• Subject meets at least 1 of the following criteria for high/very high cardiovascular (CV) risk：
• history of coronary artery disease
• history of ischemic stroke
• diagnosis of peripheral artery disease
• an estimated glomerular filtration rate (eGFR) as determined by central laboratory at screening of ≥ 30 but \< 60 ml/min/1.73m\^2
• diagnosis of diabetes mellitus type 2
• presence of ≥ 3 of the following risk factors: ≥ 45 years of age if male; ≥ 55 years of age if female; hypertension; smoking; family history of premature cardiovascular disease (CVD; 1st degree of relative: male \< 55 yr, female \< 65 yr); high-density lipoprotein (HDL) cholesterol \< 40 mg/dL; obesity (body mass index ≥ 28 kg/m\^2)
• Subject does not meet high/very high CV risk criteria but fasting LDL-C as determined by central laboratory at screening ≥ 130 mg/dl
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) by determined by central laboratory at screening
• Subject tolerates a screening placebo injection.

You may not qualify if:

• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
• Planned coronary or other revascularization within 20 weeks of screening
• New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction \< 30
• Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to randomization
• Type 1 diabetes, new-onset (hemoglobin \[Hb\]A1c ≥ 6.5% or fasting plasma glucose (FPG) ≥ 126 mg/dL at screening without known diagnosis) or poorly controlled (HbA1c ≥ 8.5%) type 2 diabetes, as determined by central laboratory at screening
• Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg
• Subject has taken a cholesterylester transfer protein (CETP) inhibitor in the 12 months prior to randomization
• Subject has taken in the 6 weeks prior to LDL-C screening: red yeast rice, \> 200 mg/day niacin, \> 1000 mg/day omega-3 fatty acids (eg, dihydroxyacetone docosahexaenoic acid and eicosapentaenoic acid), stanols or prescription lipid-regulating drugs (eg, bile-acid sequestering resins, fibrates and derivatives) or other cholesterol lowering drugs or lipid-lowering dietary supplements or food additives other than statins and ezetimibe
• Treatment 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids, (intravenous \[IV\], intramuscular \[IM\], or by-mouth \[PO\]) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane) (Note: vitamin A in a multivitamin preparation is permitted)
• Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) \< 1.0 time the lower limit of normal (LLN) or \> 1.5 times the upper limit of normal (ULN), respectively, at screening
• Severe renal dysfunction, defined as an eGFR \< 30 ml/min/1.73m\^2 at screening as estimated by Cockcroft-Gault method
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the ULN as determined by central laboratory analysis at screening
• Creatinine kinase (CK) \> 5 times the ULN at screening
• Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years prior to randomization
• Subject has previously received evolocumab or any other therapy to inhibit PCSK9

Sponsors & Collaborators

• Amgen: lead

Study Sites (31)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

Location

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510080, China

Location

Sun Yat-sen Memorial Hospital Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

Location

Guangzhou First Peoples  Hospital

Guangzhou, Guangdong, 510180, China

Location

Guangzhou Red Cross Hospital

Guangzhou, Guangdong, 510220, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

The Second Nanning Peoples Hospital

Nanning, Guangxi, 530031, China

Location

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Wuhan Puai Hospital

Wuhan, Hubei, 430030, China

Location

Changsha Central Hospital

Changsha, Hunan, 410004, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

Inner Mongolia Peoples Hospital

Hohhot, Inner Mongolia, 010017, China

Location

Suzhou Kowloon Hospital

Suzhou, Jiangsu, 215000, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221006, China

Location

Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, 212001, China

Location

The Second Affiliated Hospital to Nanchang University

Nanchang, Jiangxi, 330006, China

Location

China-Japan Union Hospital of Jilin University

Changchun, Jilin, 130033, China

Location

The Peoples Hospital of Liaoning Province

Shenyang, Liaoning, 110016, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Shanghai Yangpu District Central Hospital

Shanghai, Shanghai Municipality, 200090, China

Location

The First Affiliated Hospital of Xi An Jiao Tong University

Xi’an, Shanxi, 710061, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

Tianjin Fourth Centre Hospital

Tianjin, Tianjin Municipality, 300140, China

Location

Zhejiang Hospital

Hangzhou, Zhejiang, 310013, China

Location

Taizhou Hospital of Zhejiang Province

Linhai, Zhejiang, 317000, China

Location

Ningbo First Hospital

Ningbo, Zhejiang, 315010, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

Huashan Hospital Affiliated to Fudan University

Shanghai, 200040, China

Location

Related Publications (1)

• Tan H, Li W, Huang Z, Han Y, Huang X, Li D, Xing X, Monsalvo ML, Wu Y, Mao J, Xin L, Chen J; HUA TUO study investigators. Efficacy and Safety of Evolocumab in Chinese Patients with Primary Hypercholesterolemia and Mixed Dyslipidemia: 12-Week Primary Results of the HUA TUO Randomized Clinical Trial. Cardiol Ther. 2023 Jun;12(2):341-359. doi: 10.1007/s40119-023-00304-x. Epub 2023 Feb 21.

  PMID: 36802321 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The dose frequencies of Q2W and QM will not be blinded but the identity of investigational product (evolocumab or matching SC placebo) will be blinded. In order to protect the blinding of the double-blind treatment period the following labs will be blinded post-investigational product treatment until unblinding of the clinical database and not reported to sites as noted below: • Blinded to the Amgen study team and site staff: lipid panel, Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), lipoprotein(a), high-sensitivity C-reactive protein (hs-CRP), and Proprotein convertase subtilisin/kexin type 9 (PCSK9).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be screened for this study and if found eligible as described by the study protocol may be randomized into 1 of 4 groups. Randomized means that you are put into a group by chance. It is like drawing numbers out of a hat. Randomization will be done using a 2:2:1:1 ratio. This means for every 6 participants randomized: * 2 participants will be randomized to evolocumab 140 mg every 2 weeks * 2 participants will be randomized to evolocumab 420 mg once a month * 1 participant will be randomized to placebo every 2 weeks * 1 participant will be randomized to placebo once a month.

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: February 15, 2018
• Study Start: May 9, 2019
• Primary Completion: April 24, 2020
• Study Completion: May 9, 2020
• Last Updated: March 27, 2023
• Results First Posted: August 20, 2021

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

CN (31)