Study of the effects of blocking the enzyme PCSK9 on artery wall inflamatio

Phase 1

• Conditions: Hypercholesterolemia; MedDRA version: 18.1Level: PTClassification code 10020603Term: HypercholesterolaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2015-003731-35-NL
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-06
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

- Male or female, = 50 years of age at the time of informed consent
- Subject with fasting Lp(a) = 50 mg/dL at screening 1
- Subject with fasting LDL-C = 100 mg/dL at screening 1
- For those subjects receiving lipid lowering therapy, lipid-lowering therapy, including statin dose, must be unchanged for = 8 weeks prior to screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 84
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion Criteria

- Known diagnosis of diabetes mellitus or screening fasting serum glucose = 126 mg/dL or HbA1C = 6.5%
- A history of homozygous familial hypercholesterolemia
- Recent cardiovascular event within 3 months prior to randomization, or planned cardiac surgery, PCI or carotid stenting, or planned major non-cardiac surgery during the course of the study period
- Currently undergoing lipid apheresis
- Known contraindications or limitations to FDG-PET/ CT
- Auto-immune disease/vasculitis, active inflammatory diseases, proven or suspected bacterial infections. Recent (< 1 month prior to screening) or ongoing serious infection requiring intravenous antibiotic therapy
- Recent (< 6 weeks prior to screening) or current treatment with medications that may have a significant effect on plaque inflammation as measured by plaque TBR, including: oral, rectal, or injectable corticosteroids or immunosuppressive medications
- Recent (< 6 weeks prior to screening) or current treatment with aspirin (> 325 mg/day) or NSAIDs (> 1000 mg/day)
- Known sensitivity to any of the active substances or excipients to be administered during dosing
- Subject has taken a cholesterol ester transfer protein inhibitor or mipomersen or lomitapide in the last 12 months prior to screening
- Known systemic disorders or any clinically significant medical condition that could interfere with the conduct of the study
- History of malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years
- Subject has previously received evolocumab or any other therapy to inhibit PCSK9

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of evolocumab on arterial wall inflammation, as measured by percent change from baseline in target-to-background ratio of an index vessel by FDG-PET/CT at week 16 in subjects with baseline lipoprotein (a) [Lp(a)] = 50 mg/dL and low density lipoprotein-cholesterol (LDL-C) = 100 mg/dL;Secondary Objective: To evaluate the effect of evolocumab on <br>- Lp(a)<br>- LDL-C<br>- Apolipoprotein B (ApoB);Primary end point(s): Percent change from baseline in TBR within the MDS of the index vessel<br>(right carotid, left carotid, or thoracic aorta) by FDG-PET/CT;Timepoint(s) of evaluation of this end point: Baseline, Week 16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): [2EP-1] Percent change in Lp(a)<br>[2EP-2] Percent change in LDL-C<br>[2EP-3] Percent change in ApoB;Timepoint(s) of evaluation of this end point: [2EP-1] Baseline, Day 1, Week 8, Week 16<br>[2EP-2] Baseline, Day 1, Week 8, Week 16<br>[2EP-3] Baseline, Day 1, Week 8, Week 16