Long Term Safety Study of PRALUENT

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study was to evaluate the long term safety of PRALUENT in participants with heterozygous familial hypercholesterolemia (heFH) or non-familial hypercholesterolemia (FH) participants at high or very high cardiovascular risk who completed the neurocognitive function study R727-CL-1532 (NCT02957682). The secondary objectives of the study were: To evaluate the effect of PRALUENT on low-density lipoprotein cholesterol (LDL-C) To evaluate the effect of PRALUENT on other lipid parameters To evaluate the effect of PRALUENT on gonadal steroid hormones

Official Title
-----------------
Long Term Safety Study of PRALUENT in Patients With Heterozygous Familial Hypercholesterolemia or With Non-Familial Hypercholesterolemia at High and Very High Cardiovascular Risk and Previously Enrolled in the Neurocognitive Function Trial

Conditions
-----------------
Heterozygous Familial Hypercholesterolemia, Non-familial Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: Praluent


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Participants randomized into the neurocognitive function study (R727-CL-1532) who completed treatment and the end of study (EOS) visit with no premature or permanent discontinuation of study drug. Key Exclusion Criteria: Significant protocol deviation in the parent study (neurocognitive function study R727-CL-1532: NCT02957682) based on the investigator's or sponsor's judgment, such as noncompliance Any participant who experienced an AE leading to permanent discontinuation from the neurocognitive function study R727-CL-1532 (NCT02957682). Any new condition or worsening of an existing condition which, in the opinion of the investigator or per the PRALUENT local label, would make the participant unsuitable for enrollment or could interfere with the participant participating in or completing the open-label extension (OLE) study Known hypersensitivity to monoclonal antibody or any component of the drug product Pregnant or breastfeeding women Note: Other inclusion/ exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label<br> | Drug: Praluent<br>* Subcutaneous (SC) administration<br>* Other names: SAR236553;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks | An AE is any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. AEs include serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of special interest (AESI). AESI include local injection site reactions, general allergic events, elevated alanine aminotransferase (ALT) levels greater than or equal to (≥) 3 upper limit normal (ULN) (if baseline is less than (<) ULN)/ALT ≥2 x ULN (if baseline ≥ ULN), neurologic events, neurocognitive events (according to Customized Medical Dictionary for Regulatory Activities [MedDRA] Query [CMQ] by Sponsor grouping and CMQ by FDA grouping), cataract, new onset diabetes (NOD), hepatic disorders, and diabetes mellitus (DM)/diabetic complications. | After first administration of study drug through the last dose of study drug plus 2 weeks, up to 80 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change in LDL-C From Baseline Over Time |  | Up to week 72 | 
| Total Cholesterol (Total-C) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Total-C Over Time |  | Up to week 72 | 
| Lipoprotein a (Lp(a)) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Lp(a) Over Time |  | Up to week 72 | 
| Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Non-HDL-C Over Time |  | Up to week 72 | 
| High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in HDL-C Over Time |  | Up to week 72 | 
| Fasting Triglycerides (TGs) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Fasting TGs Over Time |  | Up to week 72 | 
| Apolipoprotein B (Apo B) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Apo B Over Time |  | Up to week 72 | 
| Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Percent Change From Baseline in Apo A1 Over Time |  | Up to week 72 | 
| Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time |  | Up to week 72 | 
| Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time |  | Up to week 72 | 
| Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time |  | Up to week 72 | 
| Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time |  | Up to week 72 | 
| Alanine Aminotransferase Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Alanine Aminotransferase Over Time |  | Up to week 72 | 
| Aspartate Aminotransferase Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Aspartate Aminotransferase Over Time |  | Up to week 72 | 
| Alkaline Phosphatase Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Alkaline Phosphatase Over Time |  | Up to week 72 | 
| Total Bilirubin Values From Baseline Over Time | The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682) | Up to week 72 | 
| Change From Baseline in Total Bilirubin Over Time |  | Up to week 72 |