Bococizumab HIV Evaluation (B-HIVE) Study
Condition: Dyslipidemia; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Dyslipidemias
Intervention: Bococizumab; Placebo
Intervention description: PF-04950615 is a humanized monoclonal antibody against the proprotein convertase subtilisin kexin type 9 (PCSK9) enzyme responsible for the degradation of the low-density lipoprotein receptor (LDLR), being developed by Pfizer, Inc for the treatment of primary hyperlipidemia and mixed dyslipidemia.; placebo
Intervention MeSH terms: Bococizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      B-HIVE is a Phase 3, double blind, placebo-controlled, randomized, parallel group study,
      designed to compare the efficacy and safety of bococizumab 150 mg subcutaneously every 2
      weeks to bococizumab placebo subcutaneously every 2 weeks for LDL-C lowering in HIV-infected
      subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Evidence of a personally signed and dated informed consent document indicating that
             the subject (or a legal representative) has been informed of all pertinent aspects of
             the study.

          2. Subjects who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

          3. Males and females greater than 40 years of age.

          4. With documented HIV infection.

          5. Moderate or high CVD risk defined as:

             documented CVD as assessed by meeting at least 1 of 3 criteria below:

               1. Coronary artery disease (CAD): prior MI due to atherosclerosis, coronary artery
                  bypass graft surgery, percutaneous coronary intervention, or angiographic CAD
                  with luminal diameter stenosis of at least one coronary artery at least 50%.

               2. Cerebrovascular disease: prior ischemic stroke of carotid origin, carotid
                  endarterectomy or stenting, or angiographic carotid stenosis of at least 50%.

               3. Peripheral arterial disease: prior lower extremity arterial surgical or
                  percutaneous revascularization procedure, or angiographic lower extremity
                  arterial stenosis of at least 50%.

             OR any one of the following CVD risk factors:

               1. Controlled type II diabetes mellitus (HbA1C ≤8.0% within the past 90 days prior
                  to study entry, regardless of use of medications)

               2. Current smoking: participant report of smoking at least a half a pack of
                  cigarettes a day, on average, in the past month.

               3. Hypertension: two consecutive BP readings with either systolic >140 mmHg or
                  diastolic >90 mmHg; or on antihypertensive medications.

               4. Dyslipidemia: defined as or HDL-C ≤ 40 mg/dL for men or ≤50 mg/dL for women,
                  regardless of medication use.

               5. a hsCRP ≥2mg/L at screening.

          6. Lipids at screening visit:

               -  Fasting LDL-C 70 mg/dL (1.81 mmol/L);

               -  Fasting TG ≤ 600 mg/dL (6.78 mmol/L).

          7. Male and female subjects of childbearing potential must agree to use a highly
             effective method of contraception throughout the study and for at least 63 days after
             the last dose of assigned treatment. A subject is of childbearing potential if, in the
             opinion of the investigator, he/she is biologically capable of having children and is
             sexually active.

        Female subjects who are not of childbearing potential (ie, meet at least one of the
        following criteria):

          -  Have undergone a documented hysterectomy or bilateral oophorectomy;

          -  Have medically confirmed ovarian failure; or

          -  Achieved post menopausal status, defined as: cessation of regular menses for at least
             12 consecutive months with no alternative pathological or physiological cause; and
             have a serum follicle stimulating hormone (FSH) level within the laboratory's
             reference range for postmenopausal females.

        Exclusion Criteria:

          1. Subjects who are investigational site staff members directly involved in the conduct
             of the trial and their family members, site staff members otherwise supervised by the
             Investigator, or subjects who are Pfizer employees.

          2. Participation in other studies involving small molecule investigational drug(s)
             (Phases 1 4) within 1 month 5 half lives, whichever is longer except for cholesteryl
             ester transfer protein (CETP) inhibitors (indefinitely), or biological agents within 6
             months or 5 half lives, whichever is longer before the current study begins and/or
             during study participation (the investigator should refer to documents provided by the
             subject on the other study to determine the investigational product half life). If the
             blind has been broken and the Investigator knows (with documentation) that the subject
             received placebo, he/she can be included.

          3. Subjects with prior exposure to bococizumab or another PCSK9 inhibitor.

          4. Subjects who are unable to receive injections, as either a self-injection, or
             administered by another person.

          5. History of a cardiovascular or cerebrovascular event or procedure (eg, myocardial
             infarction, stroke, transient ischemic attack, angioplasty) during the past 90 days.

          6. Congestive heart failure, New York Heart Association functional class IV, or left
             ventricular ejection fraction measured by imaging known to be <25%. (Imaging not
             required for study inclusion).

          7. Poorly controlled hypertension (on or off treatment) at screening visit or at
             randomization (defined as the average of two systolic blood pressure (BP) measurements
             greater than 160 mm Hg or the average of two diastolic BP measurements greater than
             100 mm Hg).

          8. Any history of hemorrhagic stroke or lacunar infarct.

          9. CD4 count at screening visit <350 cells/mm3.

         10. Current untreated hypothyroidism or thyroid stimulating hormone (TSH) >1 X upper limit
             of normal (ULN) at screening. Subjects who are treated and well controlled should be
             on a stable dose of thyroid hormone for at least 6 months.

         11. Current history of alcoholism or drug addiction according to the Diagnostic and
             Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to
             screening. Use of any recreational drugs within 12 months prior to screening.

         12. History of cancer within the last 5 years (except for cutaneous basal cell or squamous
             cell cancer resolved by excision, or cervical carcinoma in si tu).

         13. Any disease or condition that might compromise the hematological, renal, hepatic,
             pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless
             deemed not clinically significant by the Investigator and/or the Sponsor) or confound
             the interpretation of the study results. Examples of such conditions include but are
             not limited to nephrotic syndrome, uncontrolled diabetes, excessive alcohol
             consumption, cholestatic liver disease, unstable mental illness.

         14. Undergoing apheresis or have a planned start of apheresis.

         15. Initiation of or change in non-lipid lowering prescription drugs, herbal medicine or
             supplements (including foods with added plant sterols and stanols) within 6 weeks of
             screening with the exception of initiation or change in multivitamins used for general
             health purposes. Short-term use of medications to treat acute conditions, and vaccines
             are allowed (e.g., antibiotics or allergy medication).

         16. History of allergic or anaphylactic reaction to any therapeutic or diagnostic
             monoclonal antibody (IgG protein) or molecules made of components of monoclonal
             antibodies (eg, Enbrel® which contains the Fc portion of an antibody or Lucentis®
             which is a Fab).

         17. Any abnormal hematology values, clinical chemistries, or ECGs at screening judged by
             the Investigator as clinically significant, which could impact on subject safety, were
             the potential subject to be included in the study, or interfere with the
             interpretation of study results.

         18. Active phase hepatitis. Stable patients with hepatitis B or C infection >2 years
             before randomization are eligible.

         19. Aspartate transaminase (AST) or alanine transaminase (ALT) >5 X ULN at screening.

         20. Direct bilirubin >4.0 X ULN at screening.

         21. GFR <30 mL/min/1.73m2 at screening or undergoing dialysis.

         22. Plans to donate blood during the study.

         23. Pregnant females; breastfeeding females.

         24. Additional exclusion criteria for the FDG-PET/CT imaging (patients with these
             exclusions may participate in the rest of the trial):

               1. Significant radiation exposure during the year prior to randomization.
                  Significant exposure is defined as i) more than 2 PCI procedures, ii) more than 2
                  myocardial perfusion studies, or iii) more than 2 CT angiograms.

               2. Any history of radiation therapy.

               3. Current insulin use.

         25. Additional exclusion criteria for CTA imaging (patients with these exclusions may
             participate in the rest of the trial):

               1. Significant radiation exposure during the year prior to randomization.
                  Significant exposure is defined as i) more than 2 PCI procedures, ii) more than 2
                  myocardial perfusion studies, or iii) more than 2 CT angiograms (as with
                  FDG-PET/CT.

               2. Any history of radiation therapy (as with FDG-PET/CT).

               3. Any contraindication to beta-blocker or nitroglycerin use, because these drugs
                  are given as part of the standard cardiac CT protocol.

               4. Significant renal dysfunction (defined as an eGFR <60 mL/min/1.73m2).

               5. Body weight >300 pounds (136 Kg), because of the CT scanner table limitations.

               6. Allergy to iodine-containing contrast media.