Study of Evolocumab in Patients Undergoing Low-Density Lipoprotein Apheresis

• Register: EUCTR
• Last refreshed on: 13 February 2017
• Main ID: EUCTR2015-001343-37-ES
• Date of registration: 10/12/2015
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Study of Evolocumab in Patients Undergoing Low-Density Lipoprotein Apheresis
• Scientific title: A Randomized, Actively Controlled, Open-label, Multicenter Study of Efficacy and Safety of Evolocumab Compared With Low Density Lipoprotein Cholesterol (LDL-C) Apheresis, Followed by Single-Arm Evolocumab Administration in Subjects Receiving LDL-C Apheresis Prior to Study Enrollment
• Date of first enrolment: 17/12/2015
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001343-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: LDL-C apheresis Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Czech Republic, France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female, ? 18 years of age at signing of informed consent.
- Subject has been receiving regular apheresis for LDL-C lowering for at least 3 months immediately prior to lipid screening (per subject or physician report), has a treatment goal of LDL-C < 100 mg/dL (2.6 mmol/L) according to the physician managing the subject?s hypercholesterolemia, and has been receiving LDL-C apheresis during the last ? 4 weeks prior to lipid screening at regular QW or Q2W schedule and with no changes in apheresis type.
- Subject is receiving lipid-lowering pharmacological background therapy which includes a high-intensity statin dose (moderate-intensity statin dose with attestation that a higher dose is not appropriate for the subject) per Appendix D, unless the subject has a history of statin intolerance.
- Pre-apheresis LDL-C is ? 100 mg/dL (? 2.6 mmol/L) and ? 190 mg/dL (? 4.9 mmol/L) at screening.
- Fasting triglycerides ? 400 mg/dL (4.5 mmol/L) at 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 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
- Known homozygous familial hypercholesterolemia.
- Missing any apheresis session is medically contraindicated or inappropriate based on the opinion of the investigator.
- Stopping apheresis would be inappropriate in the opinion of the investigator even if LDL-C is controlled to < 100 mg/dL with other therapies (eg, subject with Lp(a) > 60 mg/dL and for whom investigator would continue apheresis for Lp(a) reduction even with LDL-C <100 mg/dL).
- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization.
- Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction (except diabetes) or receiving renal replacement therapy.
- Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg.
- Subject has taken a cholesterylester transfer protein (CETP) inhibitor such as anacetrapib, dalcetrapib or evacetrapib in the last 12 months, or mipomersen or lomitapide in the last 5 months prior to LDL-C screening.
- Subject has previously received fully human anti-PCSK9 antibody therapy (eg, evolocumab) within < 12 weeks prior to lipid screening or has received any other therapy to inhibit PCSK9 at any time.
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) or planning to receive other investigational procedures while participating in this study.
- Female subject who has (1) not used (an) acceptable method(s) of birth control for at least 1 month prior to screening and/or (2) is not willing to inform her partner of her participation in this clinical study and to use such (an) acceptable method(s) of effective birth control during treatment with IP
(evolocumab) and for an additional 15 weeks after the end of treatment with IP (evolocumab), unless the female subject is permanently sterilized or postmenopausal (see protocol);
- Subject is pregnant or breast feeding, or planning to become pregnant or planning to breastfeed during treatment with IP (evolocumab) and/or within 15 weeks after the end of treatment with IP (evolocumab).
-Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 1 year prior to screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hypercholesterolemia
MedDRA version: 18.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Evolocumab
Product Code: AMG 145
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: EVOLOCUMAB
Current Sponsor code: AMG 145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of subcutaneous (SC) evolocumab, compared to regularly scheduled LDL-C apheresis, on reducing the need for future apheresis.

Primary end point(s): Apheresis avoidance at the end of randomized therapy, defined as no apheresis at week 5 and week 6

Secondary Objective: To assess the effects of SC evolocumab compared with apheresis on percent change from baseline to week 4 in LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio

Timepoint(s) of evaluation of this end point: Weeks 5 and 6

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline and week 4

Secondary end point(s): Percent change from baseline to week 4 in the following:
? LDL-C
? non-HDL-C
? total cholesterol/HDL-C ratio

Secondary ID(s)

20140316

2015-001343-37-DE

Source(s) of Monetary Support

Amgen Inc