Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Evolocumab for LDL-C Reduction, as Add-on to Diet and Lipid-lowering Therapy, in Pediatric Subjects From 10 to 17 Years of Age With Heterozygous Familial Hypercholesterolemia (HeFH) or Homozygous Familial Hypercholesterolemia (HoFH)
- Conditions
- HoFHHypercholesterolemia - HeFH10027424
- Registration Number
- NL-OMON55627
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 25
All Subjects:
• Subject has provided written informed consent or subject assent prior to
initiation of any study-specific activities/procedures.
and/or
• Subject*s legally acceptable representative has provided informed consent
when the subject is legally too young to provide informed consent and the
subject has provided written subject assent based on local regulations and/or
guidelines prior to any study-specific activities/procedures being initiated.
Subjects with HeFH:
• Completed Study 20120123 while still on assigned investigational product.
Subjects with HoFH:
• Male or female, >= 10 to <= 17 years of age at time of enrollment (includes the
year after the subject completes the 17th year after birth but not the day of
completing the 18th year after birth).
• Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a
history of an untreated LDL cholesterol concentration > 500 mg/dL (13 mmol/L)
together with either xanthoma before 10 years of age or evidence of
heterozygous familial hypercholesterolemia in both parents.
• Subject must be on a low-fat diet and receiving background lipid-lowering
therapy (such as statins, cholesterol absorption inhibitors, bile acid
sequestrants, nicotinic acid, or combinations thereof).
• Lipid-lowering therapy, including statin dose, must be unchanged for >= 4
weeks prior to LDL-C screening; fibrates must be stable for at least 6 weeks
prior to screening.
• Fasting LDL-C at screening >= 130 mg/dL (3.4 mmol/L) as determined by central
laboratory.
• Fasting triglycerides <= 400 mg/dL (4.5 mmol/L) by central laboratory at
screening.
All Subjects:
• 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). Other investigational procedures or treatments while
participating in this study are excluded.
• Female subject who has experienced menarche and unwilling to use acceptable
method(s) of effective birth control during treatment with evolocumab and for
an additional 15 weeks after the end of treatment with evolocumab. A female who
has experienced menarche is considered of childbearing potential.
• Female subject is pregnant or breast feeding, or planning to become pregnant
or planning to breastfeed during screening, during treatment with evolocumab,
and within 15 weeks after the end of treatment with evolocumab.
• Unreliability as a study participant based on the investigator's (or
designee*s) knowledge of the subject (eg, alcohol or other drug abuse in the
past year, inability or unwillingness to adhere to the protocol, or psychosis).
• Subject will not be available for or likely not to comply with
protocol-required study visits or procedures, to the best of the subject and
investigator*s knowledge (Note: Day 1 and week 80 visits must be scheduled at
approximately the same time of day, and should be performed as close as
possible to 8 am as the hormones measured have diurnal variation).
• Known sensitivity to any of the active substances or their excipients to be
administered during dosing, eg, carboxymethylcellulose.
Subjects with HoFH:
• Moderate to severe renal dysfunction, defined as an estimated glomerular
filtration rate (eGFR) < 30 ml/min/1.73m2 at screening, confirmed by a repeat
measurement at least 1 week apart. Note: eGFR will be calculated by the central
laboratory and will be provided to the site for eligibility determination.
• Persistent active liver disease or hepatic dysfunction, defined as aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as
determined by central laboratory analysis at screening, confirmed by a repeat
measurement at least 1 week apart.
• CK > 3 times the ULN at screening, confirmed by a repeat measurement at least
1 week apart.
• Known active infection or major hematologic, renal, metabolic,
gastrointestinal or endocrine dysfunction in the judgment of the investigator.
• 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 received evolocumab or any other therapy to inhibit PCSK9 within
12 weeks of screening.
• History or evidence of any other clinically significant disorder, condition
or disease, or planned or expected procedure that, in the opinion of the
Investigator or Amgen physician, if consulted, would pose a risk to subject
safety or interfere with the study evaluation, procedures or completion.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary clinical hypothesis is that SC evolocumab will be well tolerated<br /><br>when added to standard of care in pediatric subjects 10 to 17 years of age with<br /><br>HeFH or HoFH.<br /><br>Primary Endpoint: Treatment emergent adverse events</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints:<br /><br>* Percent change from baseline at week 80 in:<br /><br>* LDL-C<br /><br>* non-HDL-C<br /><br>* ApoB<br /><br>* total cholesterol/HDL-C ratio<br /><br>* ApoB/ApoA1 ratio<br /><br>* Change from baseline in LDL-C at week 80<br /><br><br /><br>Secondary Safety Endpoints:<br /><br>* Change from baseline in steroid hormones (estradiol in females, testosterone<br /><br>in males; follicle-stimulating hormone [FSH], luteinizing hormone [LH],<br /><br>adenocorticotropic hormone [ACTH], dehydroepiandrosterone sulfate [DHEA-S],<br /><br>cortisol in all subjects) at week 80<br /><br>* Abnormal muscle and liver enzyme levels (creatine kinase [CK], aspartate<br /><br>aminotransferase [AST], or alanine aminotransferase [ALT]) at week 80<br /><br>* Change in cIMT from baseline at week 80<br /><br>* Change from baseline in growth (height and weight) and pubertal development<br /><br>(Tanner staging) at weeks 24, 48, and 80</p><br>