Bococizumab HIV Evaluation (B-HIVE) Study

• Status: Terminated
• Trial end date: 2017-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: Pfizer; San Francisco General Hospital
• Treatments: Bococizumab

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.