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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02476006
Recruitment Status : Completed
First Posted : June 19, 2015
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To provide patients with severe hypercholesterolemia at risk for subsequent cardiovascular (CV) events and not adequately controlled with currently available lipid-modifying therapy (LMT) access to alirocumab ahead of commercial availability and to document the overall safety and tolerability of alirocumab in this patient population.

Secondary Objectives:

To document the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels as well as non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels after 12 weeks of treatment.

To document patient's acceptability of self-injection (Self Injection Assessment Questionnaire, SIAQ).


Condition or disease Intervention/treatment Phase
Hypercholesterolemia Drug: ALIROCUMAB SAR236553 (REGN727) Drug: placebo (for injection training only) Phase 3

Detailed Description:
The study duration includes a screening period of up to 3 weeks, a treatment period of a minimum of 12 weeks and up to a maximum 30 months, and at least 2 weeks after the last study treatment injection.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 998 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 23, 2015
Actual Primary Completion Date : April 12, 2019
Actual Study Completion Date : April 12, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arm Intervention/treatment
Experimental: alirocumab
Periodic alirocumab subcutaneous injections, for up to 30 months
Drug: ALIROCUMAB SAR236553 (REGN727)
Pharmaceutical form:solution Route of administration: subcutaneous

Drug: placebo (for injection training only)
Pharmaceutical form:solution Route of administration: subcutaneous




Primary Outcome Measures :
  1. Proportion of patients with adverse events [ Time Frame: Up to 30 months ]

Secondary Outcome Measures :
  1. Assessment of patient's acceptability of self-injection using Self Injection Assessment Questionnaire (SIAQ) [ Time Frame: Up to 30 months ]
  2. Percent change from baseline in calculated LDL-C levels [ Time Frame: Baseline to Week 12 ]
  3. Percent change from baseline in total-C levels [ Time Frame: Baseline to Week 12 ]
  4. Percent change from baseline in HDL-C levels [ Time Frame: Baseline to Week 12 ]
  5. Percent change from baseline in TG levels [ Time Frame: Baseline to Week 12 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Patients suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations ≥160 mg/dL (4.14 mmol/L) despite treatment.

B. Patients 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 >250 mg/dL (6.46 mmol/L) at the time of the 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 <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. Patients 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%, 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 patients suffering from established CHD or other 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%, or aortic abdominal aneurysm) and with LDL-C concentrations ≥130 mg/dL (3.36 mmol/L).

E. Patients 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 LLT) 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 patients on simvastatin 80 mg for more than one year, who are 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 is a documented reason for intolerance to the abovementioned potent statins (in which case the use of a different statin is 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.

Patients 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02476006


Locations
Show Show 153 study locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02476006    
Other Study ID Numbers: LPS14245
2015-000620-28 ( EudraCT Number )
U1111-1163-0984 ( Other Identifier: UTN )
First Posted: June 19, 2015    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs