Primary HypercholesterolemiaPhase 3NCT03433755
Safety and Efficacy of Evolocumab in Addition to Optimal Stable Background Statin Therapy in Chinese Participants With Primary Hypercholesterolemia and Mixed Dyslipidemia
A Phase 3 study testing evolocumab in people with Primary Hypercholesterolemia and Mixed Dyslipidemia, run by Amgen at 31 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Primary Hypercholesterolemia, Mixed Dyslipidemia
- What is being tested?
- evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 259 participants
- Where
- 31 sitesChina
- Study dates
- 9 May 2019to 9 May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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)
- OR
- 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.
Who cannot join
- 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
Show all 34Show fewer
- 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
- Subject has known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Currently receiving treatment in another investigational device or drug study, or less than 30 days before randomization since ending treatment on another investigational device or drug study(s) or planning to receive other investigational procedures while participating in this study
- Female subject of childbearing potential not willing to use an acceptable method(s) of effective birth control during treatment with investigational product and for an additional 15 weeks after the end of treatment with investigational product. Female subjects of non-childbearing potential who are not required to use contraception during the study and include those who have had a:
- hysterectomy
- bilateral salpingectomy
- bilateral oophorectomy or
- who are postmenopausal i. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. [A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- Females on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.
- Acceptable methods of effective birth control include:
- sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments; the reliability of sexual abstinence must be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the subject. [Periodic abstinence (eg., calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception])
- bilateral tubal ligation/occlusion
- vasectomized partner (provided that partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of the surgical success)
- use of hormonal birth control methods (oral, intravaginal (eg. vaginal ring(s), transdermal, injectable, or implantable)
- intrauterine devices (IUDs)
- intrauterine hormonal releasing system (IUS)
- 2 barrier methods (each partner must use 1 barrier method) the male uses a condom and the female must choose either a diaphragm, OR cervical cap, OR contraceptive sponge with spermicide. If spermicide is not commercially available in the country or region, the 2 barrier method without spermicide is acceptable. (A female condom is not an option due to the risk of tearing when both partners use a condom.)
- Female subject is pregnant or breast feeding (nursing), planning to become pregnant or planning to breastfeed (nurse) during treatment with investigational product and/or within 15 weeks after the end of treatment with investigational product.
Trial locations and contacts
31 sites in 1 country.
31 sites in 1 country
China31 sites
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
Beijing Hospital
Beijing, Beijing Municipality, 100730
China-Japan Union Hospital of Jilin University
Changchun, Jilin, 130033
Changsha Central Hospital
Changsha, Hunan, 410004
Xiangya Hospital Central South University
Changsha, Hunan, 410008
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011
The Third Xiangya Hospital of Central South University
Changsha, Hunan, 410013
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, 510080
Sun Yat-sen Memorial Hospital Sun Yat-sen University
Guangzhou, Guangdong, 510120
Guangzhou First Peoples  Hospital
Guangzhou, Guangdong, 510180
Guangzhou Red Cross Hospital
Guangzhou, Guangdong, 510220
Zhejiang Hospital
Hangzhou, Zhejiang, 310013
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
Inner Mongolia Peoples Hospital
Hohhot, Inner Mongolia, 010017
Jinan Central Hospital
Jinan, Shandong, 250013
Taizhou Hospital of Zhejiang Province
Linhai, Zhejiang, 317000
The Second Affiliated Hospital to Nanchang University
Nanchang, Jiangxi, 330006
The Second Nanning Peoples Hospital
Nanning, Guangxi, 530031
Ningbo First Hospital
Ningbo, Zhejiang, 315010
Shanghai Yangpu District Central Hospital
Shanghai, Shanghai Municipality, 200090
Huashan Hospital Affiliated to Fudan University
Shanghai, 200040
The Peoples Hospital of Liaoning Province
Shenyang, Liaoning, 110016
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Suzhou Kowloon Hospital
Suzhou, Jiangsu, 215000
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
Tianjin Fourth Centre Hospital
Tianjin, Tianjin Municipality, 300140
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Wuhan Puai Hospital
Wuhan, Hubei, 430030
The First Affiliated Hospital of Xi An Jiao Tong University
Xi’an, Shanxi, 710061
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221006
Affiliated Hospital of Jiangsu University
Zhenjiang, Jiangsu, 212001
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab (AMG 145) in Addition to Optimal Stable Background Statin Therapy in Chinese Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
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.
Read the detailed description
This is a phase 3, multicenter, double-blind, randomized, placebo-controlled study of evolocumab in Chinese participants with hypercholesterolemia and mixed dyslipidemia. Participants who have signed the informed consent form (ICF) will have fasting lipids measured and all inclusion and exclusion criteria assessed. All eligible participants must be taking a maximum appropriate dose of an approved statin, not requiring up titration. Participants should maintain their current diet and exercise regimen.
Treatment and follow-up period will be 12 weeks with an additional phone call or other participant contact at week 14 for those receiving investigational product every 2 weeks (Q2W). The end of study (EOS) for participants on once monthly (QM) investigational product is at the week 12 visit, which must be at least 30 days post last dose of investigational product.
Evolocumab or placebo will be administered by self-injection under the skin at the study site or in an appropriate non-clinic setting (e.g., at home) by spring based prefilled auto injector/pen (AI/Pen). Participants must tolerate an injection of placebo with a prefilled auto injector/pen device to be used during the study prior to randomization.
Participants will be randomly added to 1 of 4 groups using a 2:2:1:1 ratio:
evolocumab 140 mg Q2W (86 participants total) evolocumab 420 mg QM (86 participants total) placebo Q2W (44 participants total) placebo QM (43 participants total). The dose frequencies of Q2W and QM will not be blinded but the identity of investigational product evolocumab or placebo will be blinded.
- Conditions
- Primary Hypercholesterolemia, Mixed Dyslipidemia
- Being tested
- evolocumab, placebo
- Keywords
- Evolocumab, Repatha, Statin, Chinese, China, Hypercholesterolemia, Mixed Dyslipidemia, High Cholesterol, Lowering cholesterol
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
evolocumabDrug
Also called Repatha; AMG 145
Evolocumab will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive evolocumab (AMG 145) every 2 weeks or monthly subcutaneously.
placeboDrug
Placebo will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive placebo every 2 weeks or monthly subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| Placebo Q2W | Placebo comparator | Placebo subcutaneous (SC) Q2W for 12 weeks Receives: Drug: placebo |
| Placebo QM | Placebo comparator | Placebo SC QM for 12 weeks Receives: Drug: placebo |
| Evolocumab 140 mg Q2W | Experimental | Evolocumab 140 mg SC Q2W for 12 weeks Receives: Drug: evolocumab |
| Evolocumab 420 mg QM | Experimental | Evolocumab 420 mg SC QM for 12 weeks Receives: Drug: evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, Week 12
Secondary outcomes (20)
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.
Measured: Baseline, Weeks 10 and 12
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.
Measured: Baseline, Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in Non-HDL-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.
Measured: Baseline, Week 12
Percent Change From Baseline in Apolipoprotein B (ApoB): 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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in ApoB 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.
Measured: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol: 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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol 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.
Measured: Baseline and Week 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L): Mean of Weeks 10 and 12
Percentage of participants who were below the target LDL-C of 70 mg/dL (1.8 mmol/L) based on the mean LDL-C data collected at weeks 10 and 12.
Measured: Weeks 10 and 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Measured: Week 12
Percentage of Participants With LDL-C Response: Mean of Weeks 10 and 12
Percentage of participants who had LDL-C response (50% reduction of LDL-C from baseline) based on the mean LDL-C using the data collected at weeks 10 and 12.
Measured: Baseline, Weeks 10 and 12
Percentage of Participants With LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 12
LDL-C Response is defined as a 50% reduction of LDL-C from Baseline.
Measured: Baseline and Week 12
Percent Change From Baseline in Lipoprotein(a) [Lp(a)]: 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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in Lp(a) 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.
Measured: Baseline and Week 12
Percent Change From Baseline in Triglycerides: 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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in Triglycerides 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.
Measured: Baseline and Week 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in HDL-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.
Measured: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-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.
Measured: Baseline, Weeks 10 and 12
Percent Change From Baseline in VLDL-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.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2018
- Study start9 May 2019
- Primary completion24 Apr 2020
- Study completion9 May 2020
Why it stopped: Prematurely Discontinued Amgen decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03433755
- Sponsor's protocol ID
- 20150172
- Status last verified
- Mar 2023
- First submitted
- 18 Jan 2018
- Last updated
- 27 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
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.
PubMed 36802321
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab (AMG 145) in Addition to Optimal Stable Background Statin Therapy in Chinese Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
- ClinicalTrials.gov ID
- NCT03433755
- Acronym / sponsor ID
- 20150172
- Conditions
- Primary Hypercholesterolemia, Mixed Dyslipidemia
- Keywords
- Evolocumab, Repatha, Statin, Chinese, China, Hypercholesterolemia, Mixed Dyslipidemia, High Cholesterol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Prematurely Discontinued Amgen decision
- Enrolment
- 259 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 9 May 2019 (actual)
- Primary completion
- 24 Apr 2020 (actual)
- Study completion
- 9 May 2020 (actual)
- First posted
- 15 Feb 2018 (actual)
- Results
- Posted 20 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase 3, multicenter, double-blind, randomized, placebo-controlled study of evolocumab in Chinese participants with hypercholesterolemia and mixed dyslipidemia. Participants who have signed the informed consent form (ICF) will have fasting lipids measured and all inclusion and exclusion criteria assessed. All eligible participants must be taking a maximum appropriate dose of an approved statin, not requiring up titration. Participants should maintain their current diet and exercise regimen.
Treatment and follow-up period will be 12 weeks with an additional phone call or other participant contact at week 14 for those receiving investigational product every 2 weeks (Q2W). The end of study (EOS) for participants on once monthly (QM) investigational product is at the week 12 visit, which must be at least 30 days post last dose of investigational product.
Evolocumab or placebo will be administered by self-injection under the skin at the study site or in an appropriate non-clinic setting (e.g., at home) by spring based prefilled auto injector/pen (AI/Pen). Participants must tolerate an injection of placebo with a prefilled auto injector/pen device to be used during the study prior to randomization.
Participants will be randomly added to 1 of 4 groups using a 2:2:1:1 ratio:
evolocumab 140 mg Q2W (86 participants total) evolocumab 420 mg QM (86 participants total) placebo Q2W (44 participants total) placebo QM (43 participants total). The dose frequencies of Q2W and QM will not be blinded but the identity of investigational product evolocumab or placebo will be blinded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo Q2W | Placebo comparator | Drug: placeboPlacebo subcutaneous (SC) Q2W for 12 weeks |
| Placebo QM | Placebo comparator | Drug: placeboPlacebo SC QM for 12 weeks |
| Evolocumab 140 mg Q2W | Experimental | Drug: evolocumabEvolocumab 140 mg SC Q2W for 12 weeks |
| Evolocumab 420 mg QM | Experimental | Drug: evolocumabEvolocumab 420 mg SC QM for 12 weeks |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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：
- OR
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| evolocumabAlso: Repatha; AMG 145Evolocumab will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive evolocumab (AMG 145) every 2 weeks or monthly subcutaneously. | Drug | Evolocumab 140 mg Q2W, Evolocumab 420 mg QM |
| placeboPlacebo will be administered per pre-filled auto-injector pen (AI/Pen). Participants will receive placebo every 2 weeks or monthly subcutaneously. | Drug | Placebo Q2W, Placebo QM |
Primary outcome
Co-Primary Endpoint: Percent Change From Baseline in LDL-C: Mean of Weeks 10 and 12
Time frame: Baseline, 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.
Co-Primary Endpoint: Percent Change From Baseline in LDL-C at Week 12
Time frame: Baseline, 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.
20 secondary outcomes
Change From Baseline in LDL-C: Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time frame: Baseline, Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C): Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline, Week 12
Percent Change From Baseline in Apolipoprotein B (ApoB): Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in ApoB at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Total Cholesterol: Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12
Time frame: Baseline and Week 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L): Mean of Weeks 10 and 12
Time frame: Weeks 10 and 12
Percentage of Participants With Target LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Time frame: Week 12
Percentage of Participants With LDL-C Response: Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percentage of Participants With LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Lipoprotein(a) [Lp(a)]: Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Lp(a) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Triglycerides: Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C): Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C): Mean of Weeks 10 and 12
Time frame: Baseline, Weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36802321Tan 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing evolocumab in people with Primary Hypercholesterolemia and Mixed Dyslipidemia, run by Amgen at 31 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Co-Primary Endpoint: Percent Change From Baseline in LDL-C: Mean of Weeks 10 and 12 (time frame: Baseline, Weeks 10 and 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03433755, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.