Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

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ClinicalTrials.gov Identifier: NCT03399786

Recruitment Status : Completed

First Posted : January 16, 2018

Results First Posted : May 18, 2021

Last Update Posted : May 18, 2021

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Sponsor:

Information provided by (Responsible Party):

Regeneron Pharmaceuticals

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Homozygous Familial Hypercholesterolemia
Interventions	Drug: evinacumab Drug: Placebo
Enrollment	65

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 Details	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 o...	Participants received IV infusion o...	All participants in the placebo arm...	All participants in the evinacumab ...
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
Reason Not Completed
Withdrawal by Subject	1	0	0	0
Period Title: Open-label Treatment Period (OLTP)
Started	0	0	20 ^[1]	44
Completed	0	0	19	43
Not Completed	0	0	1	1
Reason Not Completed
Noncompliance with protocol by the participant	0	0	1	0
Pregnancy	0	0	0	1
[1] One participant from the placebo group received evinacumab during the DBTP

Baseline Characteristics

Arm/Group Title		Placebo IV Q4W	Evinacumab 15 mg/kg IV Q4W	Total
Arm/Group Description		Participants received IV infusion o...	Participants received IV infusion o...	Total of all reporting groups
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 Number of Baseline Participants		22	43	65
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	22 participants	43 participants	65 participants
		36.7 (11.52)	44.3 (16.78)	41.7 (15.54)
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	22 participants	43 participants	65 participants
≥12 years to <18 years of age		1	1	2
≥18 years to <45 years of age		16	23	39
≥45 years to <65 years of age		5	11	16
≥65 years to <75 years of age		0	7	7
≥75 years of age		0	1	1
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	22 participants	43 participants	65 participants
	Female	11 50.0%	24 55.8%	35 53.8%
	Male	11 50.0%	19 44.2%	30 46.2%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	22 participants	43 participants	65 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 Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	22 participants	43 participants	65 participants
	White	17 77.3%	31 72.1%	48 73.8%
	Black or African American	0 0.0%	2 4.7%	2 3.1%
	Asian	4 18.2%	6 14.0%	10 15.4%
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Not Reported	0 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) Mean (Standard Deviation) Unit of measure: Milligrams per Deciliter (mg/dL)
	Number Analyzed	22 participants	43 participants	65 participants
		246.5 (153.71)	259.5 (172.40)	255.1 (165.21)
Apolipoprotein B (Apo B) Mean (Standard Deviation) Unit of measure: mg/dL
	Number Analyzed	22 participants	43 participants	65 participants
		175.9 (98.76)	169.1 (82.75)	171.4 (87.78)
Non-high-density Lipoprotein Cholesterol (non-HDL-C) Mean (Standard Deviation) Unit of measure: mg/dL
	Number Analyzed	22 participants	43 participants	65 participants
		269.9 (157.81)	281.9 (172.61)	277.8 (166.60)
Total Cholesterol (TC) Mean (Standard Deviation) Unit of measure: mg/dL
	Number Analyzed	22 participants	43 participants	65 participants
		315.9 (150.44)	325.6 (170.76)	322.3 (163.05)
Lipoprotein A (Lp[a]) Mean (Standard Deviation) Unit of measure: Nanomoles per Liter (nmol/L)
	Number Analyzed	22 participants	43 participants	65 participants
		103.4 (109.43)	111.3 (114.40)	108.7 (111.95)
Fasting Triglycerides (TG) Mean (Standard Deviation) Unit of measure: mg/dL
	Number Analyzed	22 participants	43 participants	65 participants
		144.1 (144.54)	113.1 (68.39)	123.6 (100.71)
Apolipoprotein CIII (Apo CIII) Mean (Standard Deviation) Unit of measure: mg/dL
	Number Analyzed	22 participants	43 participants	65 participants
		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 2...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments	[Not Specified]

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	[Not Specified]

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 repor...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments	[Not Specified]

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	[Not Specified]

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 r...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments	[Not Specified]

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	[Not Specified]

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...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments	[Not Specified]

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	[Not Specified]

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 ...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	18.2	83.7

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	[Not Specified]
	Method	Logistic Regression Models Analyses
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	25.2
	Confidence Interval	(2-Sided) 95% 5.7 to 110.5
	Estimation Comments	[Not Specified]

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 ...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	4.5	55.8

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	[Not Specified]
	Method	Logistic Regression Models Analyses
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	24.2
	Confidence Interval	(2-Sided) 95% 3.0 to 195.6
	Estimation Comments	[Not Specified]

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 DB...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Mixed-effect Model Repeat Measure (MMRM)
	Comments	[Not Specified]

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	[Not Specified]

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 inadeq...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	22.7	7.0

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. 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	[Not Specified]
	Method	Logistic Regression Models Analyses
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95% 0 to 1.3
	Estimation Comments	[Not Specified]

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...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	22.7	46.5

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	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95% 1.3 to 24.9
	Estimation Comments	[Not Specified]

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 inadeq...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	77.3	32.6

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	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95% 0.0 to 0.3
	Estimation Comments	[Not Specified]

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 We...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Measure Type: Number Unit of Measure: Percentage of Participants
	4.5	27.9

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...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 repor...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 repo...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 ...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 reporte...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 re...
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 o...	Participants received IV infusion o...
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).
Overall Number of Participants Analyzed	22	43
Least Squares Mean (Standard Error) Unit of Measure: 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 o...		Participants received IV infusion o...		All participants in the placebo arm...		All participants in the evinacumab ...
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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/21 (0.00%)		0/44 (0.00%)		0/20 (0.00%)		0/44 (0.00%)
Serious Adverse Events 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 (0.00%)		2/44 (4.55%)		0/20 (0.00%)		7/44 (15.91%)
Cardiac disorders
Acute myocardial infarction ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Angina pectoris ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Angina unstable ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Cardiac failure congestive ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Coronary artery disease ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Eye disorders
Glaucoma ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Infections and infestations
Pyelonephritis ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Urosepsis ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0	0/44 (0.00%)	0
Injury, poisoning and procedural complications
Cardiac procedure complication ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Carotid artery restenosis ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Psychiatric disorders
Suicide attempt ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0	0/44 (0.00%)	0
Renal and urinary disorders
Nephrocalcinosis ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Vascular disorders
Aortic stenosis ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
1 Term from vocabulary, MedDRA (22) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (61.90%)		20/44 (45.45%)		12/20 (60.00%)		19/44 (43.18%)
Gastrointestinal disorders
Toothache ^† 1	2/21 (9.52%)	2	2/44 (4.55%)	8	1/20 (5.00%)	1	1/44 (2.27%)	1
Nausea ^† 1	1/21 (4.76%)	1	1/44 (2.27%)	1	0/20 (0.00%)	0	3/44 (6.82%)	4
Constipation ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	2	1/20 (5.00%)	1	0/44 (0.00%)	0
Gastrooesophageal reflux disease ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
General disorders
Influenza like illness ^† 1	0/21 (0.00%)	0	5/44 (11.36%)	5	0/20 (0.00%)	0	2/44 (4.55%)	2
Infections and infestations
Nasopharyngitis ^† 1	5/21 (23.81%)	6	7/44 (15.91%)	7	1/20 (5.00%)	2	5/44 (11.36%)	5
Urinary tract infection ^† 1	2/21 (9.52%)	3	0/44 (0.00%)	0	0/20 (0.00%)	0	1/44 (2.27%)	1
Gastroenteritis viral ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	1/20 (5.00%)	1	0/44 (0.00%)	0
Influenza ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Injury, poisoning and procedural complications
Procedural headache ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Vaccination complication ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Investigations
Aspartate aminotransferase increased ^† 1	2/21 (9.52%)	2	0/44 (0.00%)	0	0/20 (0.00%)	0	0/44 (0.00%)	0
Bacterial test positive ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Serum ferritin decreased ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Musculoskeletal and connective tissue disorders
Myalgia ^† 1	2/21 (9.52%)	2	0/44 (0.00%)	0	0/20 (0.00%)	0	0/44 (0.00%)	0
Back pain ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	0/20 (0.00%)	0	3/44 (6.82%)	3
Nervous system disorders
Headache ^† 1	5/21 (23.81%)	6	4/44 (9.09%)	7	1/20 (5.00%)	2	5/44 (11.36%)	5
Psychiatric disorders
Generalised anxiety disorder ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Insomnia ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Renal and urinary disorders
Haematuria ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Reproductive system and breast disorders
Menstrual discomfort ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	1/20 (5.00%)	1	0/44 (0.00%)	0
Rhinorrhoea ^† 1	0/21 (0.00%)	0	3/44 (6.82%)	4	0/20 (0.00%)	0	0/44 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
Pruritus generalised ^† 1	0/21 (0.00%)	0	0/44 (0.00%)	0	1/20 (5.00%)	2	0/44 (0.00%)	0
Urticaria ^† 1	0/21 (0.00%)	0	1/44 (2.27%)	1	1/20 (5.00%)	1	0/44 (0.00%)	0
Vascular disorders
Hypertension ^† 1	1/21 (4.76%)	1	0/44 (0.00%)	0	1/20 (5.00%)	1	0/44 (0.00%)	0
1 Term from vocabulary, MedDRA (22) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Clinical Trials Administrator
Organization:	Regeneron Pharmaceuticals, Inc.
Phone:	844-734-6643
EMail:	clinicaltrials@regeneron.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, Ali S, Banerjee P, Chan KC, Gipe DA, Khilla N, Pordy R, Weinreich DM, Yancopoulos GD, Zhang Y, Gaudet D; ELIPSE HoFH Investigators. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Aug 20;383(8):711-720. doi: 10.1056/NEJMoa2004215.

Layout table for additonal information

Responsible Party:	Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT03399786
Other Study ID Numbers:	R1500-CL-1629 2017-001388-19 ( EudraCT Number )
First Submitted:	January 8, 2018
First Posted:	January 16, 2018
Results First Submitted:	February 12, 2021
Results First Posted:	May 18, 2021
Last Update Posted:	May 18, 2021

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