The primary objectives of the study are- To evaluate the long-term safety and tolerability of evinacumab 15 mg/kg intravenous (IV) administered every 4 weeks (Q4W) in patients with homozygous familial hypercholesterolemia (HoFH).- To evaluate the…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the incidence and severity of treatment-emergent
adverse events (TEAEs) and other safety variables during the open-label
treatment period in patients treated with evinacumab 15 mg/kg IV Q4W.
Secondary outcome
The secondary efficacy endpoints are:
- The percent and absolute change in LDL-C over time
- The percent and absolute change in Apo B over time
- The percent and absolute change in non-HDL-C over time
- The percent and absolute change in TC over time
- The percent and absolute change in TGs over time
Background summary
This study is being conducted in patients with HoFH , which may include
patients who have participated in a previous evinacumab study and also
evinacumab-naïve patients with HoFH. The study is intended to provide long-term
safety, efficacy and pharmacokinetics (PK) information on evinacumab treatment
of adult and adolescent patients in HoFH.
Hypothesis: Blockade of ANGPTL3 with evinacumab will reduce or maintain
consistent long-term reduction in LDL-C and demonstrate an acceptable safety
profile in patients with HoFH.
Study objective
The primary objectives of the study are
- To evaluate the long-term safety and tolerability of evinacumab 15 mg/kg
intravenous (IV) administered every 4 weeks (Q4W) in patients with homozygous
familial hypercholesterolemia (HoFH).
- To evaluate the long-term safety and tolerability of evinacumab 15 mg/kg IV
administered Q4W in adolescent patients with HoFH.
The secondary objectives of the study are:
- To evaluate the effect of evinacumab 15 mg/kg IV on lipid parameters (ie,
low-density lipoprotein cholesterol [LDL-C], apolipoprotein B [Apo B],
non-high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and
triglycerides [TG]) in patients with HoFH
- To evaluate the effect of evinacumab 15 mg/kg IV on lipid parameters (ie,
LDL-C, Apo B, non-HDL-C, TC, and TG) in adolescent patients with HoFH
- To evaluate the potential development of anti-evinacumab antibodies
Study design
This is an open-label study designed to evaluate the long-term safety and
efficacy of evinacumab in patients with HoFH. Eligible patients for this study
are male and female patients with HoFH, receiving stable lipid modifying
therapy (LMT), as applicable. Lipid modifying therapy may include a maximally
tolerated statin, ezetimibe, proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitor antibody and lipoprotein apheresis. Patients with HoFH who
have participated in a previous evinacumab study (eg, R1500-CL-1331 and
R1500-CL-1629) and evinacumab-naïve patients with HoFH are eligible.
This study consists of 4 periods: a run-in period, a screening period, an
open-label treatment period and a follow-up period.
Run-in Period
Patients whose HoFH diagnosis cannot be confirmed by the clinical criteria
listed or from previous genotyping results, may enter the run-in period to
determine their mutation status.
Screening period
All evinacumab-naïve patients who are on a stable background LMT will enter a
2-week screening period. Patients who participated previously in an evinacumab
study and do not enter this study within 7 days of completing the end of study
(EOS) visit of the previous study, must undergo screening.
Open-Label Treatment Period:
Patients who completed the EOS visit in the previous evinacumab study within 7
days of the baseline/day 1 visit for this open-label study do not have to
undergo the screening visit and may enroll directly into this study if they
fulfill all of the inclusion criteria and none of the exclusion criteria. The
EOS visit from the previous study can serve as the baseline/day 1 visit for
this open-label study and overlapping assessments do not need to be repeated in
this study. Baseline assessments and procedures that do not overlap with
assessments at the EOS visit of the previous study should be performed after
all EOS assessments and procedures have been completed in the previous
evinacumab study.
Starting on day 1 (baseline), all patients will receive evinacumab 15 mg/kg IV
administered every 4 weeks (Q4W). Evinacumab treatment will continue until one
of the following occurs: (1) Clinical development of evinacumab for the
indication described in this study protocol is discontinued, (2) Clinical
development of evinacumab is terminated, (3) Risk/benefit of evinacumab in this
patient population is deemed unfavorable, (4) Evinacumab is approved by the
regulatory authority governing the location of the study site, (5) For local
discontinuation of study: a decision has been made not to seek approval of an
indication for treatment of patients with HoFH in the regulatory region in
which the study is being conducted (or, to discontinue efforts to obtain such
an approval)
Follow-up period: Patients will be followed for 24 weeks after receiving the
last dose of study drug.
Intervention
Evinacumab 15 mg/kg IV administered Q4W.
Study burden and risks
Please refer to the appendix in the subject information sheet for an overview
of the risks and side effects.
Old Saw Mill River Road 777
Tarrytown 10591
US
Old Saw Mill River Road 777
Tarrytown 10591
US
Listed location countries
Age
Inclusion criteria
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
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2017-003170-13-NL |
ClinicalTrials.gov | NCT03409744 |
CCMO | NL64053.018.17 |