Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects With Genetic LDL Disorders

Amgen300 enrolled

Overview

A study to assess the long term safety and tolerability of evolocumab (AMG 145) in adolescents and adults with severe familial hypercholesterolemia.

This phase 2/3 open-label extension study was designed to characterize the safety and tolerability of long-term administration of evolocumab to adults and adolescents with severe FH (HoFH or non-HoFH severe FH). Participants not on lipid apheresis at enrollment or within the prior 8 weeks initiated treatment with evolocumab 420 mg once monthly (QM). Participants on lipid apheresis at enrollment initiated treatment with evolocumab 420 mg once every 2 weeks (Q2W). Dose frequency changes (420 mg QM vs 420 mg Q2W) were permitted at week 12, 24, or other visits with Sponsor approval. Participants with \< 5% LDL-C reduction from baseline and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) \< 100 ng/mL could discontinue evolocumab. If serum unbound PCSK9 was ≥ 100 ng/mL with QM dosing, the participant could switch to evolocumab 420 mg Q2W treatment. Participants on apheresis with ≥ 5% LDL-C reduction from baseline and serum unbound PCSK9 \< 100 ng/mL with Q2W treatment could switch to QM dosing. Participants were to continue to receive open-label evolocumab for up to 5 years or until evolocumab became commercially available in the relevant patient population, whichever occurred first.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

300

Conditions

Severe Familial Hypercholesterolemia

Interventions

EvolocumabBIOLOGICAL

Evolocumab was administered by subcutaneous injection either once a month (QM) or once every two weeks (Q2W).

Eligibility

Sex: ALLMin age: 12 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent protocol and have a diagnosis of familial hypercholesterolemia. OR * Have a diagnosis of familial hypercholesterolemia AND * Males and females ≥ 12 to ≤ 80 years of age * Stable low-fat diet and lipid-lowering therapies for at least 4 weeks * Low-density lipoprotein cholesterol (LDL-C) \>= 130 mg/dl (3.4 mmol/L) for subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C \>= 100 mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis patients have no LDL-C entry requirement * Fasting triglycerides ≤ 400 mg/dL(4.5 mmol/L) * Body weight of \> 40 kg or greater at screening for subjects less than 18 years of age Exclusion Criteria: * New York Heart Failure Association (NYHA) class III or IV or last known left ventricular ejection fraction \< 30% * Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of screening * Planned cardiac surgery or revascularization * Uncontrolled cardiac arrhythmia * Uncontrolled hypertension

Locations (44)

Outcomes

Primary Outcomes

Number of Participants With Adverse Events

The severity of each adverse event (AE) was graded according to the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) grading scale, where grade 1 = mild AE, grade 2 = moderate AE, grade 3 = severe AE, grade 4 = life-threatening AE and grade 5 = death due to AE.

Time frame: From first dose of study drug in Study 20110271 up to 30 days after the last dose or until the end of study date, whichever was earlier; median duration of treatment was 48.7 months.