Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)

• Register: ClinicalTrials.gov
• Last refreshed on: 4 April 2022
• Main ID: NCT02476006
• Date of registration: 16/06/2015
• Prospective Registration: Yes
• Primary sponsor: Sanofi
• Public title: Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)
• Scientific title: A Multi-country, Multicenter, Single-arm, Open-label Study to Document the Safety, Tolerability and Effect of Alirocumab on Atherogenic Lipoproteins in High Cardio-vascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies
• Date of first enrolment: June 23, 2015
• Target sample size: 998
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02476006
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Poland, Romania, Slovakia, Slovenia, Spain, Switzerland

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion criteria

Inclusion criteria:

Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose
of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the
screening visit (Week-3):

A. Participants suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C
concentrations greater than or equal to (>=)160 mg/dL (4.14 millimoles per liter [mmol/L])
despite treatment.

B. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L)
despite treatment and two or more CV risk factors among this list:

- LDL-C greater than (>) 250 milligrams per deciliter (mg/dL) (6.46 mmol/L) at the time
of the familial hypercholesterolemia (FH) diagnosis (before treatment).

- Family history of premature-onset coronary heart disease (CHD; first-degree male
relative with onset before age 55 years; first-degree female relative with onset
before age 65 years).

- Metabolic syndrome.

- HDL-C less than (<) 40 mg/dL (1.03 mmol/L).

- Hypertension (blood pressure >140/90 mmHg or drug treatment).

- Lipoprotein a (Lp[a]) >=50 mg/dL (1.78 µmol/L).

- Tendon xanthoma.

C. Participants suffering from heFH with LDL-C concentrations >=130 mg/dL (3.36 mmol/L)
despite treatment and one of the following characteristics:

- Established CHD or other cardiovascular disease (CVD; history of acute myocardial
infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral
arterial revascularization, stable or unstable angina, transient ischemic attack,
carotid artery stenosis >=50 percent (%), or aortic abdominal aneurysm).

- Drug-treated type 2 diabetes mellitus or type 1 with target organ damage.

- Family history of first- or second-degree relative with very premature onset CHD
(first- or second-degree male relative with onset before age 45; first- or
second-degree female relative with onset before age 55).

D. Non-FH participants suffering from established CHD or other CVD (history of acute
myocardial infarction (MI), ischemic stroke, peripheral arterial disease, coronary or
peripheral arterial revascularization, stable or unstable angina, transient ischemic
attack, carotid artery stenosis >=50%, or aortic abdominal aneurysm) and with LDL-C
concentrations >=130 mg/dL (3.36 mmol/L).

E. Participants suffering from progressive CVD (coronary artery disease, or peripheral
arterial occlusive disease or cerebrovascular disease as documented clinically or by
imaging techniques, with a subsequent CV event [acute MI, ischemic stroke, ischemia-driven
revascularization, unstable angina, transient ischemic attack] occurring despite stable
doses of maximally tolerated LMT) with LDL-C concentrations >=100 mg/dL (2.59 mmol/L).

Exclusion criteria:

Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening
visit (Week -3) and from screening to enrollment.

Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week-3) or
between screening and enrollment.

Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for
participants on simvastatin 80 mg for more than one year, who were eligible).

Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening
visit (Week-3) or between screening and enrollment, except when there was a documented
reason for intolerance to the above mentioned potent statins (in which case the use of a
different statin was allowed).

Fasting serum TG >400 mg/dL (>4.52 mmol/L) at the screening visit (Week -3). Uncontrolled
hypertension (>180 mmHg systolic and/or >110 mmHg diastolic at randomization visit).

New York Heart Association Class III or IV congestive heart failure persisting despite
treatment.

History of hemorrhagic stroke. Liver transaminases >3 times the upper limit of normal.
Laboratory evidence of current hepatitis B or C infection. Creatine kinase >3 times the
upper limit of normal. Estimated glomerular filtration rate <30 mL/min/1.73 m^2. Pregnant
or breastfeeding woman or with childbearing potential without appropriate contraception.

Male participant with a female partner of childbearing potential not protected by a
highly-effective method(s) of birth control.

Participants eligible for enrollment into an ongoing clinical study of alirocumab conducted
at the same investigational site.

Hypersensitivity to alirocumab or any of the excipients.

The above information was not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: atorvastatin

Drug: ALIROCUMAB SAR236553 (REGN727)

Drug: simvastatin

Drug: placebo (for injection training only)

Drug: rosuvastatin

Drug: ezetimibe

Primary Outcome(s)

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) [Time Frame: From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120)]

Secondary Outcome(s)

Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 [Time Frame: At Week 12]

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 [Time Frame: Baseline, Week 12]

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12 [Time Frame: At Week 12]

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [Time Frame: Baseline, Week 12]

Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use [Time Frame: Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96]

Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 [Time Frame: Baseline, Week 12]

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12 [Time Frame: Baseline, Week 12]

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12 [Time Frame: At Week 12]

Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections [Time Frame: Baseline (Pre-SIAQ), Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96]

Percent Change From Baseline in Triglycerides at Week 12 [Time Frame: Baseline, Week 12]

Secondary ID(s)

2015-000620-28

U1111-1163-0984

LPS14245

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Regeneron Pharmaceuticals

Results

• Results available: Yes
• Date Posted: 30/03/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02476006