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

Amgen

Status and phase: Completed; Phase 3; Phase 2

Conditions: Severe Familial Hypercholesterolemia

Treatments: Biological: Evolocumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01624142

20110271

2011-005400-15 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 300 patients

Sex: All

Ages: 12 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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300 participants in 1 patient group

Evolocumab

Experimental group

Description:

Participants received 420 mg evolocumab every month (participants not on lipid apheresis) or every 2 weeks (participants on lipid apheresis) for up to 5 years. Participants could switch dosing regimens at week 12 or 24 based on LDL-C and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) levels.

Treatment:

Biological: Evolocumab