Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection Clinical Trial
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
| Verified date | July 2022 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 467 |
| Est. completion date | January 27, 2020 |
| Est. primary completion date | July 9, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Darlinghurst | New South Wales |
| Australia | Research Site | East Sydney | New South Wales |
| Australia | Research Site | Fortitude Valley | Queensland |
| Australia | Research Site | Melbourne | Victoria |
| Australia | Research Site | Prahran | Victoria |
| Australia | Research Site | Sydney | New South Wales |
| Belgium | Research Site | Antwerp | |
| Belgium | Research Site | Brussels | |
| Belgium | Research Site | Gent | |
| Brazil | Research Site | Rio de Janeiro | |
| Brazil | Research Site | Sao Paulo | São Paulo |
| Brazil | Research Site | São Paulo | |
| Canada | Research Site | Calgary | Alberta |
| Canada | Research Site | Hamilton | Ontario |
| Canada | Research Site | Montreal | Quebec |
| Canada | Research Site | Quebec | |
| Canada | Research Site | Vancouver | British Columbia |
| France | Research Site | Bordeaux | |
| France | Research Site | Lyon cedex 04 | |
| France | Research Site | Montpellier cedex 5 | |
| France | Research Site | Nantes Cedex 1 | |
| France | Research Site | Paris Cedex 10 | |
| France | Research Site | Paris Cedex 12 | |
| France | Research Site | Paris Cedex 13 | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Thessaloniki | |
| Italy | Research Site | Bologna | |
| Italy | Research Site | Genova | |
| Italy | Research Site | Milano | |
| Italy | Research Site | Modena | |
| Italy | Research Site | Pisa | |
| Italy | Research Site | Roma | |
| Poland | Research Site | Warszawa | |
| Portugal | Research Site | Almada | |
| Portugal | Research Site | Aveiro | |
| Portugal | Research Site | Coimbra | |
| Portugal | Research Site | Porto | |
| Romania | Research Site | Brasov | |
| Romania | Research Site | Bucharest | |
| Romania | Research Site | Constanta | |
| Romania | Research Site | Timisoara | |
| South Africa | Research Site | Bloemfontein | |
| South Africa | Research Site | Pretoria | Gauteng |
| South Africa | Research Site | Westdene | Gauteng |
| Spain | Research Site | Barcelona | Cataluña |
| Spain | Research Site | Barcelona | Cataluña |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Madrid | |
| Switzerland | Research Site | Geneva 14 | |
| Switzerland | Research Site | Lausanne | |
| Switzerland | Research Site | Lugano | |
| Switzerland | Research Site | Zuerich | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | London | |
| United States | Research Site | Albany | New York |
| United States | Research Site | Augusta | Georgia |
| United States | Research Site | Berkley | Michigan |
| United States | Research Site | Bronx | New York |
| United States | Research Site | Camden | New Jersey |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Detroit | Michigan |
| United States | Research Site | Falls Church | Virginia |
| United States | Research Site | Hartford | Connecticut |
| United States | Research Site | Los Angeles | California |
| United States | Research Site | Miami | Florida |
| United States | Research Site | Minneapolis | Minnesota |
| United States | Research Site | New York | New York |
| United States | Research Site | Saint Louis | Missouri |
| United States | Research Site | Southfield | Michigan |
| United States | Research Site | Tampa | Florida |
| United States | Research Site | Vero Beach | Florida |
| United States | Research Site | Washington | District of Columbia |
| United States | Research Site | Washington | District of Columbia |
| United States | Research Site | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Australia, Belgium, Brazil, Canada, France, Greece, Italy, Poland, Portugal, Romania, South Africa, Spain, Switzerland, United Kingdom,
Boccara F, Caramelli B, Calmy A, Kumar P, López JAG, Bray S, Cyrille M, Rosenson RS; investigators of the BEIJERINCK study. Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period. AIDS. 2022 Apr 1;36(5):675-682. doi: 10.1097/QAD.0000000000003175. — View Citation
Boccara F, Kumar P, Caramelli B, Calmy A, López JAG, Bray S, Cyrille M, Rosenson RS. Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics. Am Heart J. 2020 Feb;220:203-212. doi: 10.1016/j.ahj.2019.11.004. Epub 2019 Nov 12. — View Citation
Boccara F, Kumar PN, Caramelli B, Calmy A, López JAG, Bray S, Cyrille M, Rosenson RS; BEIJERINCK Investigators. Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study. J Am Coll Cardiol. 2020 May 26;75(20):2570-2584. doi: 10.1016/j.jacc.2020.03.025. Epub 2020 Mar 28. Erratum in: J Am Coll Cardiol. 2020 Aug 11;76(6):762-765. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percent Change From Baseline in LDL-C at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Change From Baseline in LDL-C at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24 | Week 24 | ||
| Secondary | Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24 | Baseline, Week 24 | ||
| Secondary | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percent Change From Baseline in Total Cholesterol (TC) at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percent Change From Baseline in Triglycerides at Week 24 | 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.) | Baseline, Week 24 | |
| Secondary | Percent Change From Baseline in HDL-C at Week 24 | 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.) | Bseline, Week 24 | |
| Secondary | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24 | 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.) | Baseline, Week 24 |