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Safety, Tolerability & Efficacy on LDL-C of Evolocumab in Subjects With HIV & Hyperlipidemia/Mixed Dyslipidemia

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ClinicalTrials.gov Identifier: NCT02833844
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : November 1, 2018
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, subjects will be randomized in a ratio of 2:1 to receive either Repatha (evolocumab) QM or placebo QM.

The second part of the study is a 24-week open label extension period. During this time all subjects will receive Repatha (evolocumab) QM.

The clinical hypothesis is that subcutaneous Repatha (evolocumab) QM will be well tolerated and will result in greater reduction of LDL-C, defined as percent change from baseline at week 24, compared with placebo QM in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia.


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

Detailed Description:
LDL-C = low density lipoprotein cholesterol QM = once monthly Double blind = neither the subject, the site staff nor the Sponsor study team will know whether the subject is receiving either evolocumab or placebo Open label = all subjects receive evolocumab

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 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
Estimated Primary Completion Date : August 15, 2019
Estimated Study Completion Date : February 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: 24-week Double Blind Period Repatha (Evolocumab)
Repatha (Evolocumab) subcutaneous injection every 4 weeks (QM)
Drug: Repatha (Evolocumab)
Dose of subcutaneous Repatha (Evolocumab) every 4 weeks (QM)

Placebo Comparator: 24-week Double Blind Period Repatha (Evolocumab) Placebo
Repatha (Evolocumab) Matching Placebo subcutaneous injection every 4 weeks (QM)
Drug: Placebo
Dose of subcutaneous Repatha (Evolocumab) Matching Placebo every 4 weeks (QM)

Experimental: 24-week Open Label Period Repatha (Evolocumab)
Repatha (Evolocumab) subcutaneous injection every 4 weeks (QM)
Drug: Repatha (Evolocumab)
Dose of subcutaneous Repatha (Evolocumab) every 4 weeks (QM)




Primary Outcome Measures :
  1. Effect of Repatha (Evolocumab) on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in human immunodeficiency virus (HIV)-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    HIV = human immunodeficiency virus


Secondary Outcome Measures :
  1. Effect of Repatha (Evolocumab) on change from baseline in LDL-C in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    LDL-C=low-density lipoprotein cholesterol

  2. Effect of Repatha (Evolocumab) on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    LDL-C=low-density lipoprotein cholesterol

  3. Effect of Repatha (Evolocumab) on percent of subjects attaining a 50% reduction in LDL-C from baseline in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    LDL-C=low-density lipoprotein cholesterol

  4. Effect of Repatha (Evolocumab) on percent change from baseline in ApoB in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    ApoB=apolipoprotein B

  5. Effect of Repatha (Evolocumab) on percent change from baseline in TC in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    TC=total cholesterol

  6. Effect of Repatha (Evolocumab) on percent chang from baseline in Lp(a) in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    Lp(a)=lipoprotein(a)

  7. Effect of Repatha (Evolocumab) on percent change from baseline in triglycerides in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
  8. Effect of Repatha (Evolocumab) on percent change from baseline in HDL-C in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    HDL-C=high-density lipoprotein cholesterol

  9. Effect of Repatha (Evolocumab) on percent change from baseline in non-HDL-C in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    non-HDL-C=non-high-density lipoprotein cholesterol

  10. Effect of Repatha (Evolocumab) on percent change from baseline in VLDL-C in HIV-positive subjects with hyperlipidemia or mixed dyslipidemia [ Time Frame: Week 24 ]
    VLDL-C=very low-density lipoprotein cholesterol


Other Outcome Measures:
  1. Subject incidence of treatment emergent adverse events [ Time Frame: From date of screening until week 52 Visit (defined as end of study). ]
  2. Safety laboratory values and vital signs at each scheduled assessment [ Time Frame: From date of screening until week 52 Visit (defined as end of study). ]
  3. Incidence of anti-evolocumab antibody (binding and neutralizing) formation at each scheduled assessment [ Time Frame: From date of randomisation until week 52 Visit (defined as end of study). ]


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 (human immunodeficiency virus) infection with stable HIV therapy for ≥ 6 months
  • Cluster of differentiation 4 (CD4) ≥ 250 cells/mm3 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 astherosclerotic CVD (ASCVD), fasting LDL-C of ≥ 70 mg/dL or 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
  • NYHA III or IV heart failure, or last known left ventricular ejection fraction (LVEF) < 30%
  • Known opportunistic infection/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 cholesterylester 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


Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

  Show 79 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02833844     History of Changes
Other Study ID Numbers: 20130286
2015-004735-12 ( EudraCT Number )
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018
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

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:
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
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs