Study of Alirocumab (REGN727/SAR236553) in Patients With heFH (Heterozygous Familial Hypercholesterolemia) Who Are Not Adequately Controlled With Their LMT (Lipid-Modifying Therapy)
Condition: Heterozygous Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia
Intervention: LMT (atorvastatin, simvastatin, or rosuvastatin); alirocumab; Placebo
Intervention description: Alirocumab administered as a subcutaneous (SC) injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.; Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
Intervention MeSH terms: Atorvastatin; Rosuvastatin Calcium; Simvastatin; Alirocumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 249.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, double-blind, placebo-controlled, parallel-group, multi-national study
      alirocumab (REGN727/SAR236553) in patients with Heterozygous Familial Hypercholesterolemia
      (heFH) who are not adequately controlled with their Lipid-Modifying Therapy (LMT).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with heFH* who are not adequately controlled** with a maximally-tolerated
             daily dose*** of statin with or without other LMT, at a stable dose prior to the
             screening visit (week -2).

             *Diagnosis of heFH must be made either by genotyping or by clinical criteria. For
             those patients not genotyped, the clinical diagnosis may be based on either the Simon
             Broome criteria for definite FH (Appendix 1) or the WHO/Dutch Lipid Network criteria
             with a score of >8 points (Appendix 2).

             ** "Not adequately controlled" is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) at the
             screening visit (week -2) in patients with a history of documented CVD (Appendix 3),
             or LDL-C ≥100 mg/dL (2.59 mmol/L) at the screening visit (week -2) in patients without
             a history of documented CVD.

             *** "Maximally-tolerated dose" is defined as (any of the following are acceptable):

               -  Rosuvastatin 20 mg or 40 mg daily

               -  Atorvastatin 40 mg or 80 mg daily

               -  Simvastatin 80 mg daily (if already on this dose for >1 year - see exclusion
                  criterion #7)

             Note: Patients who are not able to be on any of the above statin doses should be
             treated with the dose of daily atorvastatin, rosuvastatin, or simvastatin which is
             considered appropriate for the patient, according to the investigator's judgment. Some
             examples of acceptable reasons for a patient taking a lower statin dose include, but
             are not limited to: adverse effects on higher doses, advanced age, low body mass
             index, regional practices, local prescribing information, concomitant medications,
             co-morbid conditions such as impaired glucose tolerance/impaired fasting glucose. The
             reason(s) will be documented in the case report form (CRF).

          2. Provide signed informed consent

        Exclusion Criteria:

          1. Patient without diagnosis of heFH made either by genotyping or by clinical criteria

          2. LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (week-2) in patients with
             history of documented cardiovascular disease

          3. LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (week -2) in patients without
             history of documented cardiovascular disease

          4. Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate
             for at least 6 weeks, as applicable, prior to the screening visit (week -2) and from
             screening to randomization

          5. Currently taking another statin than simvastatin, atorvastatin, or rosuvastatin

          6. Simvastatin, atorvastatin, or rosuvastatin is not taken daily or not taken at a
             registered dose

          7. Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except
             for patients on simvastatin 80 mg for more than 1 year, who are eligible)

          8. Use of fibrates, other than fenofibrate within 6 weeks of the screening visit (week-2)
             or between screening and randomization visits

          9. Use of nutraceutical products or over-the-counter therapies that may affect lipids
             which have not been at a stable dose/amount for at least 4 weeks prior to the
             screening visit (week -2) or between screening and randomization visits

         10. Use of red yeast rice products within 4 weeks of the screening visit (week-2), or
             between screening and randomization visits

         11. Patient who has received plasmapheresis treatment within 2 months prior to the
             screening visit (week -2), or has plans to receive it during the study

         12. Recent (within 3 months prior to the screening visit [week -2] or between screening
             and randomization visits) MI, unstable angina leading to hospitalization, percutaneous
             coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled
             cardiac arrhythmia, stroke, transient ischemic attack (TIA), carotid
             revascularization, endovascular procedure or surgical intervention for peripheral
             vascular disease

        (The inclusion/exclusion criteria provided above is not intended to contain all
        considerations relevant to a participant's potential participation in this clinical trial).