Brief Summary
The study is divided into 2 parts. The first part of the study will be double-blinded and will last for 24 weeks. During this time, participants will be randomized in a ratio of 2:1 to receive either evolocumab once monthly (QM) or placebo QM. The second part of the study is a 24-week open label extension period. During this time all participants will receive evolocumab QM.
The clinical hypothesis is that subcutaneous evolocumab QM will be well tolerated and will result in greater reduction of low density lipoprotein cholesterol (LDL-C), defined as percent change from baseline at Week 24, compared with placebo QM in human immunodeficiency virus (HIV)-positive participants with hyperlipidemia or mixed dyslipidemia.
The clinical hypothesis is that subcutaneous evolocumab QM will be well tolerated and will result in greater reduction of low density lipoprotein cholesterol (LDL-C), defined as percent change from baseline at Week 24, compared with placebo QM in human immunodeficiency virus (HIV)-positive participants with hyperlipidemia or mixed dyslipidemia.
Brief Title
Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia
Categories
Completion Date
Completion Date Type
Actual
Conditions
Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection
Eligibility Criteria
Inclusion Criteria:
* Male or female ≥ 18 years of age
* Known HIV infection with stable HIV therapy for ≥ 6 months
* Cluster of differentiation 4 (CD4) ≥ 250 cells/mm\^3 for ≥ 6 months
* HIV viral load ≤ 50 copies/mL at screening and ≤ 200 copies/mL for ≥ 6 months
* Subject on stable lipid-lowering therapy for ≥ 4 weeks prior to randomization and not expected to change during the duration of study
* For subjects with known clinical atherosclerotic cardiovascular disease (ASCVD), fasting LDL-C of ≥ 70 mg/dL or non-high density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL. For subjects without known clinical ASCVD: fasting LDL-C of ≥ 100 mg/dL or non-HDL-C of ≥ 130 mg/dL
* Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L)
Exclusion Criteria:
* Taking a combination of background lipid-lowering therapy and HIV therapy known to have significant drug-drug interaction
* New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction (LVEF) \< 30%
* Known opportunistic infection/acquired immunodeficiency syndrome (AIDS) defining illness within 1 year prior to randomization
* Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months
* Type 1 diabetes, new-onset or poorly controlled type 2 diabetes
* Uncontrolled hypertension
* Taken a cholesteryl ester transfer protein inhibitor in the last 12 months
* Moderate to severe renal dysfunction
* Persistent active liver disease or hepatic dysfunction (Stable chronic hepatitis C of at least 1 year duration prior to randomization is allowed)
* 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
Other exclusion criteria may apply.
* Male or female ≥ 18 years of age
* Known HIV infection with stable HIV therapy for ≥ 6 months
* Cluster of differentiation 4 (CD4) ≥ 250 cells/mm\^3 for ≥ 6 months
* HIV viral load ≤ 50 copies/mL at screening and ≤ 200 copies/mL for ≥ 6 months
* Subject on stable lipid-lowering therapy for ≥ 4 weeks prior to randomization and not expected to change during the duration of study
* For subjects with known clinical atherosclerotic cardiovascular disease (ASCVD), fasting LDL-C of ≥ 70 mg/dL or non-high density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL. For subjects without known clinical ASCVD: fasting LDL-C of ≥ 100 mg/dL or non-HDL-C of ≥ 130 mg/dL
* Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L)
Exclusion Criteria:
* Taking a combination of background lipid-lowering therapy and HIV therapy known to have significant drug-drug interaction
* New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction (LVEF) \< 30%
* Known opportunistic infection/acquired immunodeficiency syndrome (AIDS) defining illness within 1 year prior to randomization
* Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months
* Type 1 diabetes, new-onset or poorly controlled type 2 diabetes
* Uncontrolled hypertension
* Taken a cholesteryl ester transfer protein inhibitor in the last 12 months
* Moderate to severe renal dysfunction
* Persistent active liver disease or hepatic dysfunction (Stable chronic hepatitis C of at least 1 year duration prior to randomization is allowed)
* 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
Other exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Male or female ≥ 18 years of age
* Known HIV infection with stable HIV therapy for ≥ 6 months
* Cluster of differentiation 4 (CD4) ≥ 250 cells/mm\^3 for ≥ 6 months
* HIV viral load ≤ 50 copies/mL at screening and ≤ 200 copies/mL for ≥ 6 months
* Subject on stable lipid-lowering therapy for ≥ 4 weeks prior to randomization and not expected to change during the duration of study
* For subjects with known clinical atherosclerotic cardiovascular disease (ASCVD), fasting LDL-C of ≥ 70 mg/dL or non-high density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL. For subjects without known clinical ASCVD: fasting LDL-C of ≥ 100 mg/dL or non-HDL-C of ≥ 130 mg/dL
* Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L)
* Male or female ≥ 18 years of age
* Known HIV infection with stable HIV therapy for ≥ 6 months
* Cluster of differentiation 4 (CD4) ≥ 250 cells/mm\^3 for ≥ 6 months
* HIV viral load ≤ 50 copies/mL at screening and ≤ 200 copies/mL for ≥ 6 months
* Subject on stable lipid-lowering therapy for ≥ 4 weeks prior to randomization and not expected to change during the duration of study
* For subjects with known clinical atherosclerotic cardiovascular disease (ASCVD), fasting LDL-C of ≥ 70 mg/dL or non-high density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL. For subjects without known clinical ASCVD: fasting LDL-C of ≥ 100 mg/dL or non-HDL-C of ≥ 130 mg/dL
* Fasting triglycerides ≤ 600 mg/dL (6.8 mmol/L)
Gender
All
Gender Based
false
Keywords
Hyperlipidemia
Dyslipidemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Inhibition
HIV infection
Cluster of differentiation
Viral load
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02833844
Org Class
Industry
Org Full Name
Amgen
Org Study Id
20130286
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Double Blind, Randomized, Placebo Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy on LDL-C of Evolocumab (AMG 145) in Subjects With HIV and With Hyperlipidemia and/or Mixed Dyslipidemia
Primary Outcomes
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Measure
Percent Change From Baseline in LDL-C at Week 24
Outcome Time Frame
Baseline, Week 24
Secondary Ids
Secondary Id
2015-004735-12
Secondary Outcomes
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Change From Baseline in LDL-C at Week 24
Outcome Time Frame
Week 24
Outcome Measure
Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Total Cholesterol (TC) at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Triglycerides at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Bseline, Week 24
Outcome Measure
Percent Change From Baseline in HDL-C at Week 24
Outcome Description
Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)
Outcome Time Frame
Baseline, Week 24
Outcome Measure
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276