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Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia

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ClinicalTrials.gov Identifier: NCT02833844
Recruitment Status : Completed
First Posted : July 14, 2016
Results First Posted : July 21, 2020
Last Update Posted : January 29, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

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.


Condition or disease Intervention/treatment Phase
Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection Drug: Evolocumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 467 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 22, 2017
Actual Primary Completion Date : July 9, 2019
Actual Study Completion Date : January 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Evolocumab

Arm Intervention/treatment
Experimental: Double-Blind Placebo SC QM/Open-Label Evolocumab 420 mg SC QM
Double-blind placebo subcutaneous (SC) injection every 4 weeks (QM) for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.
Drug: Evolocumab
Dose of subcutaneous evolocumab QM
Other Names:
  • EvoMab
  • Repatha
  • AMG 145

Drug: Placebo
Dose of matching placebo QM

Placebo Comparator: Double-Blind Evolocumab 420 mg SC QM/Open-Label Evolocumab 420 mg SC QM
Double-blind evolocumab SC injection QM for 24 weeks, followed by open-label evolocumab 420 mg SC QM for 24 weeks.
Drug: Evolocumab
Dose of subcutaneous evolocumab QM
Other Names:
  • EvoMab
  • Repatha
  • AMG 145




Primary Outcome Measures :
  1. Percent Change From Baseline in LDL-C at Week 24 [ Time Frame: Baseline, 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.)


Secondary Outcome Measures :
  1. Change From Baseline in LDL-C at Week 24 [ Time Frame: Baseline, 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.)

  2. Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24 [ Time Frame: Week 24 ]
  3. Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24 [ Time Frame: Baseline, Week 24 ]
  4. Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24 [ Time Frame: Baseline, 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.)

  5. Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 [ Time Frame: Baseline, 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.)

  6. Percent Change From Baseline in Total Cholesterol (TC) at Week 24 [ Time Frame: Baseline, 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.)

  7. Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24 [ Time Frame: Baseline, 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.)

  8. Percent Change From Baseline in Triglycerides at Week 24 [ Time Frame: Baseline, 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.)

  9. Percent Change From Baseline in HDL-C at Week 24 [ Time Frame: Bseline, 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.)

  10. Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24 [ Time Frame: Baseline, 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.)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833844


Locations
Show Show 78 study locations
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] January 30, 2017
Statistical Analysis Plan  [PDF] January 20, 2019

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02833844    
Other Study ID Numbers: 20130286
2015-004735-12 ( EudraCT Number )
First Posted: July 14, 2016    Key Record Dates
Results First Posted: July 21, 2020
Last Update Posted: January 29, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Hyperlipidemia
Dyslipidemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Inhibition
HIV infection
Cluster of differentiation
Viral load
Additional relevant MeSH terms:
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HIV Infections
Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Evolocumab
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents