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Study of Evolocumab in Patients Undergoing Low-Density Lipoprotein Apheresis

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
EUCTR2015-001343-37-ES
Lead Sponsor
Amgen Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
50
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
;
- 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
;
- 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.
;
- 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.
;
- 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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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