Long Term Safety Study of PRALUENT

Phase 4

Terminated

• Conditions: Heterozygous Familial Hypercholesterolemia; Non-familial Hypercholesterolemia
• Interventions: Drug: Praluent

• Registration Number: NCT03694197
• Lead Sponsor: Regeneron Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-06
• Study Start: 2018-09-28
• Study First Submitted QC: 2018-10-01
• Study First Posted: 2018-10-03
• Primary Completion: 2020-04-08
• Study Completion: 2020-04-08
• Results First Submitted: 2021-04-06
• Status Verified: 2021-05
• Results First Submitted QC: 2021-05-20
• Last Update Submitted: 2021-05-20
• Results First Posted: 2021-06-15
• Last Update Posted: 2021-06-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1389

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

1. 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
2. Any participant who experienced an AE leading to permanent discontinuation from the neurocognitive function study R727-CL-1532 (NCT02957682).
3. 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
4. Known hypersensitivity to monoclonal antibody or any component of the drug product
5. Pregnant or breastfeeding women

Note: Other inclusion/ exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	Praluent	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks	After first administration of study drug through the last dose of study drug plus 2 weeks, up to 80 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time	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	Up to week 72	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)
Percent Change From Baseline in Apo B Over Time	Up to week 72
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time	Up to week 72	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)
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time	Up to week 72	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)
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time	Up to week 72	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)
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time	Up to week 72
Total Cholesterol (Total-C) Values From Baseline Over Time	Up to week 72	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)
Percent Change From Baseline in Total-C Over Time	Up to week 72
Lipoprotein a (Lp(a)) Values From Baseline Over Time	Up to week 72	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)
Percent Change From Baseline in Fasting TGs Over Time	Up to week 72
Percent Change From Baseline in Apo A1 Over Time	Up to week 72
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time	Up to week 72	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)
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time	Up to week 72	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)
Change From Baseline in Alanine Aminotransferase Over Time	Up to week 72
Change From Baseline in Aspartate Aminotransferase Over Time	Up to week 72
Change From Baseline in Alkaline Phosphatase Over Time	Up to week 72
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time	Up to week 72	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)
Percent Change in LDL-C From Baseline Over Time	Up to week 72
Percent Change From Baseline in Lp(a) Over Time	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	Up to week 72	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)
Apolipoprotein B (Apo B) Values From Baseline Over Time	Up to week 72	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)
Total Bilirubin Values From Baseline Over Time	Up to week 72	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)
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time	Up to week 72	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)
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time	Up to week 72
Alanine Aminotransferase Values From Baseline Over Time	Up to week 72	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)
Aspartate Aminotransferase Values From Baseline Over Time	Up to week 72	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)
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time	Up to week 72
Alkaline Phosphatase Values From Baseline Over Time	Up to week 72	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)
Change From Baseline in Total Bilirubin Over Time	Up to week 72

Trial Locations

Locations (5)

Regeneron Research Site; 🇺🇦 Vinnytsya, Ukraine

Regeneron Research Site 2; 🇷🇺 Yaroslavl, Russian Federation

Regeneron Research Site #2; 🇺🇦 Kyiv, Ukraine

Regeneron Research Site 3; 🇺🇸 Knoxville, Tennessee, United States

Regeneron Research Site 1; 🇷🇺 Yaroslavl, Russian Federation