Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03399786
• Collaborator: (none)
• Enrollment: 65
• Locations: 30
• Arms: 2
• Actual Duration (Months): 25.9
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab intravenously (IV) in comparison to placebo after 24 weeks in patients with homozygous familial hypercholesterolemia (HoFH). The secondary objectives of the study are to evaluate the effect of evinacumab IV on other lipid parameters, evaluate the effect of evinacumab on LDL-C goal attainment, assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria), evaluate the safety and tolerability of evinacumab in patients with HoFH, assess the pharmacokinetics (PK) of evinacumab in patients with HoFH and evaluate the potential development of anti-evinacumab antibodies.

Condition or Disease	Intervention/Treatment	Phase
Homozygous Familial Hypercholesterolemia	Drug: evinacumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
• Actual Study Start Date: Jan 18, 2018
• Actual Primary Completion Date: Jun 10, 2019
• Actual Study Completion Date: Mar 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: evinacumab	Drug: evinacumab; IV administration of evinacumab; Other Names: REGN1500
Experimental: Placebo	Drug: Placebo; IV administration of placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand) [Week 24]

   Percent change was calculated as 100x(calculated LDL-C value at Week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. The baseline LDL-C value was the last calculated LDL-C value obtained before the first dose of double-blind-study drug. The calculated LDL-C at week 24 was the LDL-C value obtained within the week 24 efficacy analysis window, regardless of adherence to treatment and subsequent therapies (intent-to-treat [ITT] estimand). The ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

Secondary Outcome Measures

1. Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand) [Week 24]

   Percent change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

2. Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand) [Week 24]

   Percent change from baseline in non-HDL-C at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

3. Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand) [Week 24]

   Percent change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

4. Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) [At Week 24]

   Percentage of participants who achieved reduction in calculated LDL-C ≥30% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

5. Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand) [At Week 24]

   Percentage of participants who achieved reduction in calculated LDL-C ≥ 50% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

6. Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand) [Week 24]

   Absolute change in calculated LDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

7. Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) [At Week 24]

   US apheresis eligibility criteria included participants who had inadequate response to diet and LMTs after 6 months of treatment and with functional Homozygous familial hypercholesterolemia (HoFH) or Heterozygous familial hypercholesterolemia (HeFH) (with 0-1 risk factor) with LDL-C ≥ 300 mg/dL (7.77 mmol/L). Percentage of participants who met US apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

8. Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand) [At Week 24]

   Percentage of participants with LDL-C value <100 mg/dL (2.59 mmol/L) in the DBTP at Week 24 was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analysed according to the treatment group allocated by randomization (i.e., as randomized participant group).

9. Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand) [At Week 24]

   EU apheresis eligibility criteria included participants who had inadequate response to diet and Lipid modifying therapies (LMTs) after 3 months of treatment, Primary prevention: Participants with Familial hypercholesterolemia (FH) with LDL-C >160 mg/dL (4.2 mmol/L) and Cardiovascular (CV) events in close relatives. Secondary prevention: Participants with progressive CV events with LDL-C > 120 to 130 mg/dL (3.1-3.4 mmol/L). Percentage of participants who met EU apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

10. Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand) [At Week 24]

    Percentage of participants with LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

11. Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Percent change from baseline in TG at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

12. Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Percent change in Lp(a) from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

13. Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Absolute change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

14. Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Absolute change in non-HDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

15. Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Absolute change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

16. Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand) [Week 24]

    Percent change in Apo CIII from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Diagnosis of functional HoFH

2. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks

3. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study

Key Exclusion Criteria:

1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit

2. Background medical Lipid Modifying Therapy (LMT) (if applicable) that has not been stable before the screening visit

3. Lipid-apheresis schedule /apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit

4. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit

5. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins

6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled (HbA1c >9%) diabetes

7. History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit

8. Pregnant or breastfeeding women

9. Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug

10. Men who are sexually active with women of child bearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period and for 24 weeks after the last dose of study drug regardless of vasectomy status

Note: Other protocol defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regeneron Research Site	Boca Raton	Florida	United States	33434
2	Regeneron Research Site	Boston	Massachusetts	United States	02114
3	Regeneron Research Site	New York	New York	United States	10029
4	Regeneron Research Site	Cincinnati	Ohio	United States	45227
5	Regeneron Research Site	Portland	Oregon	United States	97239
6	Regeneron Research Site	Dallas	Texas	United States	78226
7	Regeneron Research Site	Camperdown	New South Wales	Australia	2050
8	Regeneron Research Site	Perth	Western Australia	Australia	6000
9	Regeneron Research Site	Innsbruck		Austria	6020
10	Regeneron Research Site	Chicoutimi	Quebec	Canada	G7H 7K9
11	Regeneron Research Site	Québec	Quebec	Canada	G1V 4W2
12	Regeneron Research Site	Paris	Cedex	France	75651
13	Regeneron Research Site	Marseille		France	13385
14	Regeneron Research Site	Ioánnina	Ioannina	Greece	45500
15	Regeneron Research Site	Athens		Greece	17674
16	Regeneron Research Site # 2	Napoli		Italy	80131
17	Regeneron Research Site	Kurume	Fukuoka	Japan	830-8522
18	Regeneron Research Site	Nishinomiya	Hyogo	Japan	662-0918
19	Regeneron Research Site	Kanazawa	Ishikawa	Japan	920-8641
20	Regeneron Research Site #3	Suita	Osaka	Japan	565-0871
21	Regeneron Research Site	Suita	Osaka	Japan	565-8565
22	Regeneron Research Site	Osaka		Japan	530-0001
23	Regeneron Research Site	Amsterdam		Netherlands	1105 AZ
24	Regeneron Research Site	Rotterdam		Netherlands	3045 PM
25	Regeneron Research Site	Parktown	Johannesburg	South Africa	2000
26	Regeneron Research Site	Ivano-Frankivs'k		Ukraine	76075
27	Regeneron Research Site	Kharkiv		Ukraine	61039
28	Regeneron Research Site #2	Kharkiv		Ukraine	61176
29	Regeneron Research Site #2	Kyiv		Ukraine	02660
30	Regeneron Research Site	Kyiv		Ukraine	03680

Sponsors and Collaborators

• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Oct 11, 2019
• Statistical Analysis Plan - Jul 16, 2019

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03399786
• Other Study ID Numbers: R1500-CL-1629; 2017-001388-19
• First Posted: Jan 16, 2018
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Regeneron Pharmaceuticals: HoFH
• Additional relevant MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia

Study Results

Participant Flow

Recruitment Details	This study was conducted at 30 centers that enrolled participants in 11 countries in Europe, Asia, North America, and Australia. Randomization was stratified by apheresis treatment status and by region (Japan, Rest of the World [ROW]).
Pre-assignment Detail	A total of 75 participants were screened and 65 participants randomized. There were 10 participants that were considered screen failures.

Arm/Group Title	Placebo IV Q4W (DBTP)	Evinacumab 15 mg/kg (DBTP)	Placebo IV Q4W (OLTP)	Evinacumab 15 mg/kg (OLTP)
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP).	All participants in the placebo arm who completed the double-blind treatment period (DBTP) received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	All participants in the evinacumab arm who completed the double-blind treatment period (DBTP) received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Period Title: Double-blind Treatment Period (DBTP)
STARTED	22	43	0	0
COMPLETED	21	43	0	0
NOT COMPLETED	1	0	0	0
Period Title: Double-blind Treatment Period (DBTP)
STARTED	0	0	20	44
COMPLETED	0	0	19	43
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W	Total
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Total of all reporting groups
Overall Participants	22	43	65
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.7 (11.52)	44.3 (16.78)	41.7 (15.54)
Age, Customized (Number) [Number]
≥12 years to <18 years of age	1 4.5%	1 2.3%	2 3.1%
≥18 years to <45 years of age	16 72.7%	23 53.5%	39 60%
≥45 years to <65 years of age	5 22.7%	11 25.6%	16 24.6%
≥65 years to <75 years of age	0 0%	7 16.3%	7 10.8%
≥75 years of age	0 0%	1 2.3%	1 1.5%
Sex: Female, Male (Count of Participants)
Female	11 50%	24 55.8%	35 53.8%
Male	11 50%	19 44.2%	30 46.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.5%	1 2.3%	2 3.1%
Not Hispanic or Latino	20 90.9%	38 88.4%	58 89.2%
Unknown or Not Reported	1 4.5%	4 9.3%	5 7.7%
Race (Count of Participants)
White	17 77.3%	31 72.1%	48 73.8%
Black or African American	0 0%	2 4.7%	2 3.1%
Asian	4 18.2%	6 14%	10 15.4%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Not Reported	0 0%	2 4.7%	2 3.1%
Other	1 4.5%	2 4.7%	3 4.6%
Calculated Low-density Lipoprotein Cholesterol (LDL-C) (Milligrams per Deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Milligrams per Deciliter (mg/dL)]	246.5 (153.71)	259.5 (172.40)	255.1 (165.21)
Apolipoprotein B (Apo B) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	175.9 (98.76)	169.1 (82.75)	171.4 (87.78)
Non-high-density Lipoprotein Cholesterol (non-HDL-C) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	269.9 (157.81)	281.9 (172.61)	277.8 (166.60)
Total Cholesterol (TC) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	315.9 (150.44)	325.6 (170.76)	322.3 (163.05)
Lipoprotein A (Lp[a]) (Nanomoles per Liter (nmol/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Nanomoles per Liter (nmol/L)]	103.4 (109.43)	111.3 (114.40)	108.7 (111.95)
Fasting Triglycerides (TG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	144.1 (144.54)	113.1 (68.39)	123.6 (100.71)
Apolipoprotein CIII (Apo CIII) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	9.7 (5.23)	9.2 (4.00)	9.39 (4.42)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (Intent-to-Treat [ITT] Estimand)
Description	Percent change was calculated as 100x(calculated LDL-C value at Week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. The baseline LDL-C value was the last calculated LDL-C value obtained before the first dose of double-blind-study drug. The calculated LDL-C at week 24 was the LDL-C value obtained within the week 24 efficacy analysis window, regardless of adherence to treatment and subsequent therapies (intent-to-treat [ITT] estimand). The ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	1.9 (6.5)	-47.1 (4.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	Confidence interval (CI) with p-value was based on-treatment group difference of least squares (LS) means using mixed-effect model repeat measurement (MMRM), randomization strata, treatment/strata/baseline value-by-time point interaction and continuous fixed covariates of baseline calculated LDL-C value.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-49.0
	Confidence Interval	(2-Sided) 95%; -65.0 to -33.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.0
	Estimation Comments

2. Secondary Outcome

Title	Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
Description	Percent change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	-4.5 (4.8)	-41.4 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. CI with p-value was based on-treatment group difference of LS means using MMRM, randomization strata, treatment/strata/baseline value-by-time point interaction and continuous fixed covariates of baseline calculated Apo B value.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-36.9
	Confidence Interval	(2-Sided) 95%; -48.6 to -25.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.9
	Estimation Comments

3. Secondary Outcome

Title	Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
Description	Percent change from baseline in non-HDL-C at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	2.0 (5.4)	-49.7 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. CI with p-value was based on-treatment group difference of LS means using MMRM, randomization strata, treatment/strata/baseline value-by-time point interaction and continuous fixed covariates of baseline calculated non-HDL-C value.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-51.7
	Confidence Interval	(2-Sided) 95%; -64.8 to -38.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.6
	Estimation Comments

4. Secondary Outcome

Title	Percent Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
Description	Percent change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	1.0 (4.2)	-47.4 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. CI with p-value was based on-treatment group difference of LS means using MMRM, randomization strata, treatment/strata/baseline value-by-time point interaction and continuous fixed covariates of baseline calculated TC value.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-48.4
	Confidence Interval	(2-Sided) 95%; -58.7 to -38.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.1
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With ≥30% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
Description	Percentage of participants who achieved reduction in calculated LDL-C ≥30% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	18.2 82.7%	83.7 194.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for secondary endpoints in pre-specified order to control type I error.Testing sequence continued only when previous endpoint was statistically significant at 0.05.Multiple imputation addressed missing data at week 24.Combined estimate for odds ratio obtained by Rubin's formulae.Logistic regression models stratified by randomized strata include fixed categorical effect of treatment group & continuous fixed covariate of baseline calculated LDL-C.
	Type of Statistical Test	Superiority
	Comments	A 2-step multiple imputation method addressed missing values (seeds = 1629 & 9261 with number of imputations = 100 in first and number of imputation=1 in second step).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Logistic Regression Models Analyses
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	25.2
	Confidence Interval	(2-Sided) 95%; 5.7 to 110.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With ≥50% Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 (ITT Estimand)
Description	Percentage of participants who achieved reduction in calculated LDL-C ≥ 50% at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	4.5 20.5%	55.8 129.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for secondary endpoints in pre-specified order to control type I error.Testing sequence continued only when previous endpoint was statistically significant at 0.05.Multiple imputation addressed missing data at week 24.Combined estimate for odds ratio obtained by Rubin's formulae.Logistic regression models stratified by randomized strata include fixed categorical effect of treatment group & continuous fixed covariate of baseline calculated LDL-C.
	Type of Statistical Test	Superiority
	Comments	A 2-step multiple imputation method addressed missing values (seeds = 1629 & 9261 with number of imputations = 100 in first and number of imputation=1 in second step).
Statistical Test of Hypothesis	p-Value	= 0.0028
	Comments
	Method	Logistic Regression Models Analyses
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	24.2
	Confidence Interval	(2-Sided) 95%; 3.0 to 195.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Absolute Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 (ITT Estimand)
Description	Absolute change in calculated LDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Milligrams per Deciliter (mg/dL)]	-2.6 (17.6)	-134.7 (12.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. CI with p-value was based on-treatment group difference of LS means using MMRM, randomization strata, treatment/strata/baseline value-by-time point interaction and continuous fixed covariates of baseline calculated LDL-C value.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-132.1
	Confidence Interval	(2-Sided) 95%; -175.3 to -88.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 21.5
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants Who Met United States (US) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
Description	US apheresis eligibility criteria included participants who had inadequate response to diet and LMTs after 6 months of treatment and with functional Homozygous familial hypercholesterolemia (HoFH) or Heterozygous familial hypercholesterolemia (HeFH) (with 0-1 risk factor) with LDL-C ≥ 300 mg/dL (7.77 mmol/L). Percentage of participants who met US apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	22.7 103.2%	7.0 16.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Combined estimate for odds ratio was obtained by using Rubin's formulae. Logistic regression models stratified the fixed categorical effect of treatment group and the continuous fixed covariate of baseline calculated LDL-C value.
	Type of Statistical Test	Superiority
	Comments	A 2-step multiple imputation method addressed missing values (seeds = 1629 & 9261 with number of imputations = 100 in first and number of imputation=1 in second step).
Statistical Test of Hypothesis	p-Value	= 0.0845
	Comments
	Method	Logistic Regression Models Analyses
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; 0 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Low-Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter (mg/dL) (2.59 Millimoles Per Liter [mmol/L]) at Week 24 (ITT Estimand)
Description	Percentage of participants with LDL-C value <100 mg/dL (2.59 mmol/L) in the DBTP at Week 24 was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analysed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	22.7 103.2%	46.5 108.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Combined estimate for odds ratio was obtained by using Rubin's formulae. Logistic regression models stratified the fixed categorical effect of treatment group and the continuous fixed covariate of baseline calculated LDL-C value.
	Type of Statistical Test	Superiority
	Comments	A 2-step multiple imputation method addressed missing values (seeds = 1629 & 9261 with number of imputations = 100 in first and number of imputation=1 in second step).
Statistical Test of Hypothesis	p-Value	= 0.0203
	Comments	The p-value is nominal for descriptive purpose only due to statistical hypothesis testing terminated previously.
	Method	Logistic Regression Models Analyses
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; 1.3 to 24.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants Who Met European Union (EU) Apheresis Eligibility Criteria at Week 24 (ITT Estimand)
Description	EU apheresis eligibility criteria included participants who had inadequate response to diet and Lipid modifying therapies (LMTs) after 3 months of treatment, Primary prevention: Participants with Familial hypercholesterolemia (FH) with LDL-C >160 mg/dL (4.2 mmol/L) and Cardiovascular (CV) events in close relatives. Secondary prevention: Participants with progressive CV events with LDL-C > 120 to 130 mg/dL (3.1-3.4 mmol/L). Percentage of participants who met EU apheresis eligibility criteria at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	77.3 351.4%	32.6 75.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo IV Q4W, Evinacumab 15 mg/kg IV Q4W
	Comments	A 2-sided hierarchical testing procedure was used for the secondary endpoints in a pre-specified order to control type I error. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Combined estimate for odds ratio was obtained by using Rubin's formulae. Logistic regression models stratified the fixed categorical effect of treatment group and the continuous fixed covariate of baseline calculated LDL-C value.
	Type of Statistical Test	Superiority
	Comments	A 2-step multiple imputation method addressed missing values (seeds = 1629 & 9261 with number of imputations = 100 in first and number of imputation=1 in second step).
Statistical Test of Hypothesis	p-Value	= 0.0004
	Comments	The p-value is nominal for descriptive purpose only due to statistical hypothesis testing terminated previously.
	Method	Logistic Regression Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With Calculated Low-Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL (1.81 mmol/L) at Week 24 (ITT Estimand)
Description	Percentage of participants with LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Number [Percentage of Participants]	4.5 20.5%	27.9 64.9%

12. Secondary Outcome

Title	Percent Change in Fasting Triglycerides (TG) From Baseline to Week 24 (ITT Estimand)
Description	Percent change from baseline in TG at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	-4.6 (7.0)	-55.0 (3.1)

13. Secondary Outcome

Title	Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 (ITT Estimand)
Description	Percent change in Lp(a) from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	-3.6 (5.8)	-5.5 (4.0)

14. Secondary Outcome

Title	Absolute Change in Apolipoprotein B (Apo B) From Baseline to Week 24 (ITT Estimand)
Description	Absolute change in Apo B from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [mg/dL]	-8.0 (9.1)	-74.4 (6.3)

15. Secondary Outcome

Title	Absolute Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 (ITT Estimand)
Description	Absolute change in non-HDL-C from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [mg/dL]	-0.4 (17.4)	-148.0 (12.3)

16. Secondary Outcome

Title	Absolute Change in Total Cholesterol (TC) From Baseline to Week 24 (ITT Estimand)
Description	Absolute change in TC from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [mg/dL]	-0.4 (17.2)	-161.6 (12.2)

17. Secondary Outcome

Title	Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline to Week 24 (ITT Estimand)
Description	Percent change in Apo CIII from baseline at Week 24 in the DBTP was reported; value obtained regardless of adherence to study treatment and subsequent therapies (ITT estimand). ITT population included all randomized participants who received at least one dose or part of a dose of double-blind study drug. Participants in the ITT population were analyzed according to the treatment group allocated by randomization (i.e., as randomized participant group).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).	Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP). All participants who completed the double-blind treatment period received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
Measure Participants	22	43
Least Squares Mean (Standard Error) [Percent Change]	5.8 (5.5)	-84.1 (3.9)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up until end of study (Week 68) regardless of seriousness or relationship to investigational product (IP).
Adverse Event Reporting Description	For purpose of safety analysis, arm assignments for participants in Safety Set were based on actual treatment received, such that 1 participant assigned to Placebo arm who inadvertently received evinacumab 15mg/kg was included in Evinacumab 15mg/kg arm
Arm/Group Title	Placebo IV Q4W (DBTP)		Evinacumab 15 mg/kg (DBTP)		Placebo IV Q4W (OLTP)		Evinacumab 15 mg/kg (OLTP)
Arm/Group Description	Participants received IV infusion of placebo matched to evinacumab every 4 weeks (Q4W) from day 1 to week 20 in the double-blind treatment period (DBTP).		Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from day 1 to week 20 in the double-blind treatment period (DBTP).		All participants in the placebo arm who completed the double-blind treatment period (DBTP) received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).		All participants in the evinacumab arm who completed the double-blind treatment period (DBTP) received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from week 24 to week 44 in the open-label treatment period (OLTP).
All Cause Mortality
	Placebo IV Q4W (DBTP)		Evinacumab 15 mg/kg (DBTP)		Placebo IV Q4W (OLTP)		Evinacumab 15 mg/kg (OLTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/44 (0%)		0/20 (0%)		0/44 (0%)
Serious Adverse Events
	Placebo IV Q4W (DBTP)		Evinacumab 15 mg/kg (DBTP)		Placebo IV Q4W (OLTP)		Evinacumab 15 mg/kg (OLTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		2/44 (4.5%)		0/20 (0%)		7/44 (15.9%)
Cardiac disorders
Acute myocardial infarction	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Angina pectoris	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Angina unstable	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Cardiac failure congestive	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Coronary artery disease	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Eye disorders
Glaucoma	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Infections and infestations
Pyelonephritis	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Urosepsis	0/21 (0%)	0	1/44 (2.3%)	1	0/20 (0%)	0	0/44 (0%)	0
Injury, poisoning and procedural complications
Cardiac procedure complication	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Carotid artery restenosis	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Psychiatric disorders
Suicide attempt	0/21 (0%)	0	1/44 (2.3%)	1	0/20 (0%)	0	0/44 (0%)	0
Renal and urinary disorders
Nephrocalcinosis	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Vascular disorders
Aortic stenosis	0/21 (0%)	0	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Placebo IV Q4W (DBTP)		Evinacumab 15 mg/kg (DBTP)		Placebo IV Q4W (OLTP)		Evinacumab 15 mg/kg (OLTP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)		20/44 (45.5%)		12/20 (60%)		19/44 (43.2%)
Gastrointestinal disorders
Toothache	2/21 (9.5%)	2	2/44 (4.5%)	8	1/20 (5%)	1	1/44 (2.3%)	1
Nausea	1/21 (4.8%)	1	1/44 (2.3%)	1	0/20 (0%)	0	3/44 (6.8%)	4
Constipation	0/21 (0%)	0	1/44 (2.3%)	2	1/20 (5%)	1	0/44 (0%)	0
Gastrooesophageal reflux disease	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
General disorders
Influenza like illness	0/21 (0%)	0	5/44 (11.4%)	5	0/20 (0%)	0	2/44 (4.5%)	2
Infections and infestations
Nasopharyngitis	5/21 (23.8%)	6	7/44 (15.9%)	7	1/20 (5%)	2	5/44 (11.4%)	5
Urinary tract infection	2/21 (9.5%)	3	0/44 (0%)	0	0/20 (0%)	0	1/44 (2.3%)	1
Gastroenteritis viral	0/21 (0%)	0	1/44 (2.3%)	1	1/20 (5%)	1	0/44 (0%)	0
Influenza	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Injury, poisoning and procedural complications
Procedural headache	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Vaccination complication	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Investigations
Aspartate aminotransferase increased	2/21 (9.5%)	2	0/44 (0%)	0	0/20 (0%)	0	0/44 (0%)	0
Bacterial test positive	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Serum ferritin decreased	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	2/21 (9.5%)	2	0/44 (0%)	0	0/20 (0%)	0	0/44 (0%)	0
Back pain	0/21 (0%)	0	1/44 (2.3%)	1	0/20 (0%)	0	3/44 (6.8%)	3
Nervous system disorders
Headache	5/21 (23.8%)	6	4/44 (9.1%)	7	1/20 (5%)	2	5/44 (11.4%)	5
Psychiatric disorders
Generalised anxiety disorder	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Insomnia	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Renal and urinary disorders
Haematuria	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Reproductive system and breast disorders
Menstrual discomfort	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/21 (0%)	0	1/44 (2.3%)	1	1/20 (5%)	1	0/44 (0%)	0
Rhinorrhoea	0/21 (0%)	0	3/44 (6.8%)	4	0/20 (0%)	0	0/44 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0
Pruritus generalised	0/21 (0%)	0	0/44 (0%)	0	1/20 (5%)	2	0/44 (0%)	0
Urticaria	0/21 (0%)	0	1/44 (2.3%)	1	1/20 (5%)	1	0/44 (0%)	0
Vascular disorders
Hypertension	1/21 (4.8%)	1	0/44 (0%)	0	1/20 (5%)	1	0/44 (0%)	0

Limitations/Caveats

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.