An open-label study to evaluate the long-term safety and efficacy of evinacumab in patients with homozygous familial hypercholesterolemia
- Conditions
- hereditary abnormal high cholesterol levelhomozygous familial hypercholesterolemia1008362410013317
- Registration Number
- NL-OMON55891
- Lead Sponsor
- Regeneron Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
A patient must meet the following criteria to be eligible for inclusion in the
study:
1. Male and female patients >=12 years of age with HoFH. Patients aged >=12
years old will be enrolled only in countries where permitted by the Regulatory
Agency and Institutional Review Board (IRB) or Ethics Committee (EC).
2. Diagnosis of functional HoFH by at least 1 of the following genetic or
clinical criteria:
a. Documented functional mutation or mutations in both LDLR alleles
Note: patients who have null receptor mutations on both LDLR alleles, ie,
double null, are eligible
b. Presence of homozygous or compound heterozygous mutations in Apo B or PCSK9
Note: patients who are double heterozygous, ie, mutations on different genes
(eg, LDLR/PCSK9) and patients with homozygous LDLRAP1 mutations are eligible
c. Untreated TC >500 mg/dL (12.93 mmol/L) and TG <300 mg/dL (3.39 mmol/L)
AND
both parents with documented TC >250 mg/dL (6.47 mmol) OR cutaneous or
tendinous xanthoma before the age of 10 years
3. For patients who have participated in a previous evinacumab or alirocumab
study: completion of the study in which they participated.
4. Willing and able to comply with clinic visits and study-related procedures.
5. Provide signed informed consent.
Exclusion Criteria for Evinacumab-Naïve Patients, A patient who meets any of
the following criteria will be excluded from the study:
1. Concomitant medications and procedures that have not been stable prior to
the baseline visit (see Section 7.7.2 for medications and procedures and their
associated required duration of therapy).
2. Any new condition or worsening of an existing condition, which in the
opinion of the investigator would make the patient unsuitable for enrollment,
or could interfere with the patient participating in or completing the study.
3. History of a MI, unstable angina leading to hospitalization, coronary artery
bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac
arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack,
valve replacement surgery, carotid revascularization, endovascular procedure or
surgical intervention for peripheral vascular disease within 3 months prior to
the baseline visit
4. Presence of any clinically significant uncontrolled endocrine disease known
to influence serum lipids or lipoproteins
Note: patients on thyroid replacement therapy can be included if the dosage of
replacement therapy has been stable for at least 12 weeks prior to screening
and the thyroid stimulating hormone (TSH) level is within the normal range of
the central laboratory at the screening visit
5. Newly diagnosed (within 3 months prior to screening visit diabetes mellitus
or poorly controlled (HbA1c >9%) diabetes
6. Use of systemic corticosteroids, unless used as replacement therapy for
pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to
screening visit
Note: topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies
are not considered as *systemic* and are allowed
7. Use of estrogen or testosterone therapy unless the regimen has been stable 6
weeks prior to the screening visit and no plans to change the regimen during
the study
8. Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at
the screening visit
9. History of cancer within the past 5 years, except for adequately treated
basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
10. History of New York Heart Association (NYHA) Class IV heart failure within
12 months before screening. Please refer to the protocol for exclusion criteria
11 - 19. Exclusion Criteria for Patients from a Previous Evinacumab Study, A
patient who meets any of the following criteria will be excluded from the study:
1. Significant protocol deviation in the previous study based on the
investigator*s judgment, such as non-compliance by the patient.
2. Concomitant medications and procedures that have not been stable prior to
the baseline visit (see Section 7.7.2 for medications and procedures and their
associated required duration of therapy).
3. Adverse event leading to permanent discontinuation from previous study.
4. Any new condition or worsening of an existing condition, which in the
opinion of the
investigator would make the patient unsuitable for enrollment, or could
interfere with the patient participating in or completing the study. Please
refer to the protocol for exclusion criteria 5 - 19.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the incidence and severity of treatment-emergent<br /><br>adverse events (TEAEs) and other safety variables during the open-label<br /><br>treatment period in patients treated with evinacumab 15 mg/kg IV Q4W.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary efficacy endpoints are:<br /><br>- The percent and absolute change in LDL-C over time<br /><br>- The percent and absolute change in Apo B over time<br /><br>- The percent and absolute change in non-HDL-C over time<br /><br>- The percent and absolute change in TC over time<br /><br>- The percent and absolute change in TGs over time</p><br>