Regeneron Hypercholesterolemia Study

Overview

Status: Recruiting
Keywords: Familial Hypercholesterolemia
IRB Number: 00057404
Specialty: Cardiology
Sub Specialties: Cardiac Electrophysiology

Brief Summary

The primary objective of the study is to assess the pharmacodynamic effect of REGN727 on serum low-density lipoprotein cholesterol during 14 weeks of subcutaneously administered REGN727 in patients with autosomal dominant hypercholesterolemia and gain-of-function mutations (GOFm) in 1 or both alleles of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene.

The secondary objectives of the study are to assess in patients with PCSK9 GOFm: 

1.     The safety and tolerability of SC administered REGN727

2.     The PD effect of REGN727 on other serum lipids/Apolipoproteins including: total cholesterol, HDL-C, non-HDL-C, very low-density lipoprotein cholesterol (VLDL-C), TG, ApoB100, ApoA1, and Lp(a)

3.     The PK profile of multiple SC doses of REGN727

4.     The immunogenicity profile in patients after 14 weeks of dosing with REGN727.

5.     Patients will be required to provide a blood sample for genetic testing.  Genes are made up of DNA, which is the substance in cells that carries genetic (inherited) information.  The genes contain key instructions for cell function and help determine the characteristics of each individual. Patients are required to provide one DNA sample for the main study.  This sample will be used only to test the genes PCSK9, LDLR, and APOB.  You already had the DNA for PCSK9 tested.  They play an important role in how much cholesterol circulates in your blood.  We will test these genes again to confirm the results of the testing that was performed on them in the past.

6.   After completing the first 15 visits (blinded portion), participants will be invited to continue the study drug as part of an open-label treatment study for approximately 3 years or until approval of the study drug. Participants will continue to receive 150 mg REGN727 to assess the long-term safety and durability of the effect of REGN727 on lipids and lipoproteins.

Principal Investigator: Paul Hopkins
Department: Cardiovascular Genetics
Co Investigator:

Contact Information

Name:Sawsan Ibrahim
Phone: (801) 581-3810
Email: sawsan.ibrahim@utah.edu

Inclusion Criteria

Inclusion Criteria:

1.               Men and women between the ages of 18 and 70 years, inclusive.

2.               A history of molecularly confirmed PCSK9 GOFm or loss of function mutations in apo B.

3.               Plasma LDL-C levels greater than or equal to 70 mg/dL at the screening visit on a lipid lowering regimen stable for at least 28 days; LDL-C mush be considered to be not at goal by the investigator.

4.               BMI 18 to 40 kg/m2 at the screening visit.

5.               Systolic blood pressure less than 150 mm Hg and diastolic BP less than 95 mm Hg at the screening visit.

6.               Participant must be willing to consumption no more than 2 standard alcoholic drinks in any 24-hour period for the duration of the study.  A standard alcoholic drink is the equivalent of 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of hard liquor.

7.               The participant must be willing to refrain from the consumption of alcohol for 24 hours prior to each study visit.

8.               Participants must be willing to maintain their usual stable diet and exercise regimen throughout the study.

9.               Participants must be willing and able to comply with the schedule of clinic visits and study-related procedures.

10.            Participants must provide signed informed consent.

 

Exclusion Criteria

 

A patient who meets any of the following criteria will be excluded from the study:

1.               Serum TG >350 mg/dL at the screening visit (visit 1 [day -28 to day -15]) measured after an 8 to 12 hour fast

2.               History of heart failure (New York Heart Association Class II-IV) within the 12 months before the screening visit

3.               History of myocardial infarction, acute coronary syndrome (ACS), unstable angina pectoris, stroke, peripheral vascular disease, transient ischemic attack, or cardiac revascularization within the 6 months before the screening visit

4.               History of uncontrolled, clinically significant cardiac dysrhythmias or clinically significant recent changes in ECG 6 months before the screening visit

5.               Known history of active optic nerve disease

6.               History of undergoing LDL apheresis within 3 months before the screening visit

7.               Uncontrolled diabetes mellitus with hemoglobin A1C (HbA1c) >8.5% at the screening visit (visit 1 [day -28 to -15])

8.               Thyroid stimulating hormone (TSH) >1.5 x upper limit of normal (ULN) at the screening visit

9.               Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x ULN at the full screening visit (1 repeat lab is allowed)

10.            Total creatine phosphokinase (CPK) >3 x ULN at the screening visit (1 repeat lab is allowed)

11.            Known sensitivity to monoclonal antibody therapeutics

12.            Participation in a clinical research study evaluating an investigational drug within 30 days, or at least 5 half-lives of the investigational drug, before the screening visit, whichever is longer

13.            Known to be positive for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus

14.            History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases

15.            Pregnant or breast-feeding women

16.            Sexually active man* or woman of childbearing potential** who is unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly)

17.            Any medical or psychiatric condition which, in the opinion of the investigator, would place the patient at risk, interfere with patient’s participation in the study or interfere with the interpretation of the study results.

18.          Red yeast rice will be prohibited during the study.

 

*Acceptable contraceptive measures or postmenopausal status refer to the man’s sexual partner or to men with documented vasectomy.

**Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.