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Clinical Trial Results:
A Three-Part, Single-Arm, Open-Label Study To Evaluate The Efficacy, Safety, And Pharmacokinetics Of Evinacumab In Pediatric Patients With Homozygous Familial Hypercholesterolemia

Summary
EudraCT number	2019-001931-30
Trial protocol	AT NL
Global end of trial date	30 May 2023

Results information
Results version number	v1(current)
This version publication date	13 Dec 2023
First version publication date	13 Dec 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

R1500-CL-17100

ISRCTN number

US NCT number

NCT04233918

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron Pharmaceuticals, Inc.

Sponsor organisation address

777 Old Saw Mill River Road, Tarrytown, NY, United States, 10591

Public contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com

Scientific contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002298-PIP01-17

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

30 May 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 May 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective for Part A of the study is to assess the pharmacokinetics (PK) of evinacumab in pediatric participants with homozygous familial hypercholesterolemia (HoFH). The primary objective for Part B of the study is to demonstrate a reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab in pediatric (5 to 11 years of age) participants with HoFH.

Protection of trial subjects

It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Jun 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

Austria: 5

Country: Number of subjects enrolled

Netherlands: 4

Country: Number of subjects enrolled

Taiwan: 2

Country: Number of subjects enrolled

United States: 7

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 23 participants were screened to Part A and Part B. 6 participants were enrolled in Part A, 14 participants in Part B. 3 participants were considered screen failures. 2 withdrew consent, 1 due to Other. Participants who enrolled in Part A of study were not eligible to participate in Part B. All 20 participants completed part C.

Period 1 title

Period 1: Part A and B

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A: Evinacumab 15mg/Kg IV

Arm description

In Part A, Participants received single IV infusion of evinacumab at a dose of 15 mg/kg on Day 1.

Arm type

Experimental

Investigational medicinal product name

evinacumab

Investigational medicinal product code

R1500

Other name

Evkeeza

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received a single dose of evinacumab 15 milligrams per kilogram (mg/kg) administered by intravenous (IV) infusion

Part B: Evinacumab 15mg/Kg IV Q4W

Arm description

In Part B, Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 24.

Arm type

Experimental

Investigational medicinal product name

evinacumab

Investigational medicinal product code

R1500

Other name

Evkeeza

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received evinacumab 15 milligrams per kilogram (mg/kg) administered by intravenous (IV) infusion every four weeks (Q4W) from Week 0 to Week 24

Number of subjects in period 1	Part A: Evinacumab 15mg/Kg IV	Part B: Evinacumab 15mg/Kg IV Q4W
Started	6	14
Completed	6	14

Period 2 title

Part C (Extension Period)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A to C

Arm description

All participants who completed Part A received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Arm type

Experimental

Investigational medicinal product name

evinacumab

Investigational medicinal product code

R1500

Other name

Evkeeza

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All participants from Part A who entered Part C initially received open-label evinacumab 15 mg/kg IV Q4W. The final dose in Part C was the same as the dose in Part B, 15 mg/kg IV Q4W, during the 48 week treatment period.

Part B to C

Arm description

All participants who completed Part B received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Arm type

Experimental

Investigational medicinal product name

evinacumab

Investigational medicinal product code

R1500

Other name

Evkeeza

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All participants from Part B who entered Part C initially received open-label evinacumab 15 mg/kg IV Q4W. The final dose in Part C was the same as the dose in Part B, 15 mg/kg IV Q4W, during the 48 week treatment period.

Number of subjects in period 2	Part A to C	Part B to C
Started	6	14
Completed	6	14

Baseline characteristics

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Reporting group title

Part A: Evinacumab 15mg/Kg IV

Reporting group description

In Part A, Participants received single IV infusion of evinacumab at a dose of 15 mg/kg on Day 1.

Reporting group title

Part B: Evinacumab 15mg/Kg IV Q4W

Reporting group description

In Part B, Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 24.

Reporting group values	Part A: Evinacumab 15mg/Kg IV	Part B: Evinacumab 15mg/Kg IV Q4W	Total
Number of subjects	6	14	20
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	6	14	20
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	0	0	0
From 65-84 years	0	0	0
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	8.8 ( 1.72 )	9.1 ( 1.94 )	-
Sex: Female, Male
Units: participants
Female	4	8	12
Male	2	6	8
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	1	1
Asian	0	2	2
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	1	1
White	6	8	14
More than one race	0	0	0
Unknown or Not Reported	0	2	2
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	0	1
Not Hispanic or Latino	5	13	18
Unknown or Not Reported	0	1	1

End points

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Reporting group title

Part A: Evinacumab 15mg/Kg IV

Reporting group description

In Part A, Participants received single IV infusion of evinacumab at a dose of 15 mg/kg on Day 1.

Reporting group title

Part B: Evinacumab 15mg/Kg IV Q4W

Reporting group description

In Part B, Participants received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 24.

Reporting group title

Part A to C

Reporting group description

All participants who completed Part A received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Reporting group title

Part B to C

Reporting group description

All participants who completed Part B received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Primary: Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab

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End point title

Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab ^[1] ^[2]

End point description

Cmax was obtained directly from the plasma concentration versus time curve.

End point type

Primary

End point timeframe

At day 12

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analysis was used for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part A only

End point values	Part A: Evinacumab 15mg/Kg IV
Number of subjects analysed	6
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard deviation)	238 ( 90.8 )

No statistical analyses for this end point

Primary: Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab

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End point title

Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab ^[3] ^[4]

End point description

AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.

End point type

Primary

End point timeframe

Pre-dose at Week 0; End of infusion at Week 0.006, 1, 2, 4, 8 and 12

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analysis was used for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part A only

End point values	Part A: Evinacumab 15mg/Kg IV
Number of subjects analysed	6
Units: DaysMilligrams per Liter (daymg/L)
arithmetic mean (standard deviation)	4576 ( 1568 )

No statistical analyses for this end point

Primary: Part A: Terminal Half-Life (t1/2) of Evinacumab

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End point title

Part A: Terminal Half-Life (t1/2) of Evinacumab ^[5] ^[6]

End point description

T1/2 was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.

End point type

Primary

End point timeframe

Pre-dose at Week 0; End of infusion at Week 0.006, 1, 2, 4, 8 and 12

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analysis was used for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part A only

End point values	Part A: Evinacumab 15mg/Kg IV
Number of subjects analysed	6
Units: Days
median (full range (min-max))	7.69 (6.18 to 12.4)

No statistical analyses for this end point

Primary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24

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End point title

Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 ^[7] ^[8]

End point description

Percent change was calculated as 100 multiplied by (calculated LDL-C value at Week 24 minus calculated LDL-C value at baseline) divided by calculated LDL-C value at baseline.

End point type

Primary

End point timeframe

Baseline to Week 24

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analysis was used for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (confidence interval 95%)	-48.3 (-68.8 to -27.8)

No statistical analyses for this end point

Secondary: Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24

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End point title

Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24 ^[9]

End point description

Percent change in Apo B from baseline to Week 24 was reported.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (confidence interval 95%)	-41.3 (-58.9 to -23.8)

No statistical analyses for this end point

Secondary: Part A and Part B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Part A and Part B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

End point description

Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAE was defined as AE starting/worsening after first intake of study drug. TEAE included participants with both serious and non-serious AEs.

End point type

Secondary

End point timeframe

Part A: up to Week 24; Part B: up to Week 48

End point values	Part A: Evinacumab 15mg/Kg IV	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	6	14
Units: Participants	5	10

No statistical analyses for this end point

Secondary: Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24

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End point title

Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24 ^[10]

End point description

Percentage of participants who achieved reduction in calculated LDL-C ≥ 50% at Week 24 was reported.

End point type

Secondary

End point timeframe

Week 24

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percentage of Participants
number (not applicable)	78.6

No statistical analyses for this end point

Secondary: Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24

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End point title

Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24 ^[11]

End point description

Percent change in Lp(a) from baseline to Week 24 was reported.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (confidence interval 95%)	-37.3 (-42.2 to -32.3)

No statistical analyses for this end point

Secondary: Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24

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End point title

Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24 ^[12]

End point description

Percent change in TC from baseline to Week 24 was reported.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (confidence interval 95%)	-49.1 (-64.9 to -33.2)

No statistical analyses for this end point

Secondary: Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24

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End point title

Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24 ^[13]

End point description

Percent change in Non-HDL-C from baseline to Week 24 was reported.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (confidence interval 95%)	-48.9 (-68.1 to -29.7)

No statistical analyses for this end point

Secondary: Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24

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End point title

Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24 ^[14]

End point description

Absolute change in LDL-C from baseline at Week 24 was reported

End point type

Secondary

End point timeframe

Baseline, Week 24

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Milligrams per Deciliter (mg/dL)
arithmetic mean (standard error)	-131.9 ( 30.0 )

No statistical analyses for this end point

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have Negative/Negative and Null/Null Mutations

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End point title

Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have Negative/Negative and Null/Null Mutations ^[15]

End point description

Participants with HoFH was classified based on the phenotype of the Low-density lipoprotein receptor (LDLR) mutation(s), ranging from defective mutations (where the LDLR retains some LDL-binding functionality) to null or negative mutations where no functioning LDLR was expressed. Participants who have LDLR activity <15% are considered null and participants whose LDLR activity was impaired but >15% are LDLR defective. Percent change in calculated LDL-C from baseline to Week 24 in participants who have negative/negative and null/null mutations was reported.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	4
Units: Percent Change
arithmetic mean (standard error)
Negative/negative mutations (n=3)	-67.7 ( 6.5 )
Null/Null mutations (n=1)	-57.2 ( 99999 )

No statistical analyses for this end point

Secondary: Part B: Serum Concentration of Total Evinacumab

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End point title

Part B: Serum Concentration of Total Evinacumab ^[16]

End point description

Serum concentration of total evinacumab was reported. Pre-dose samples at week 0 were assayed and the reported value is based on actual measurement.

End point type

Secondary

End point timeframe

Pre-dose at Weeks 0, 4, 8, 12; End of infusion at Weeks 0.006, 4.006, 8.006, 12.006 and 24

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard deviation)
Week 0	0 ( 0 )
Week 0.006	256 ( 58.0 )
Week 4	62.6 ( 22.6 )
Week 4.006	293 ( 92.3 )
Week 8	98.8 ( 37.7 )
Week 8.006	356 ( 76 )
Week 12	120 ( 46.5 )
Week 12.006	363 ( 82.1 )
Week 24	140 ( 92.5 )

No statistical analyses for this end point

Secondary: Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab

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End point title

Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab ^[17]

End point description

Maximum serum concentration (Cmax,ss) steady state following drug administration.

End point type

Secondary

End point timeframe

Post-dose on Days 1, 29, 57, 85 and 169

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard deviation)	428.9 ( 113.7 )

No statistical analyses for this end point

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have by null/null vs. non-null/null and negative/negative vs.non-negative/negative Mutations

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End point title

Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have by null/null vs. non-null/null and negative/negative vs.non-negative/negative Mutations ^[18]

End point description

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Percent Change
arithmetic mean (standard error)
Negative/Negative	-67.7 ( 6.5 )
Non-Negative/Negative	-43.0 ( 12.8 )
Null/Null	-57.2 ( 99999 )
Non-Null/Null	-47.6 ( 11.3 )

No statistical analyses for this end point

Secondary: Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab

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End point title

Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab ^[19]

End point description

Ctrough.ss was defined as minimum serum concentration at steady state of evinacumab

End point type

Secondary

End point timeframe

Post-dose on Days 1, 29, 57, 85 and 169

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard deviation)	171.8 ( 79.5 )

No statistical analyses for this end point

Secondary: Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab

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End point title

Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab ^[20]

End point description

AUCtau.ss was defined as area under the serum concentration-time curve at steady state of evinacumab

End point type

Secondary

End point timeframe

Post-dose on Days 1, 29, 57, 85 and 169

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was pre-specified for Part B only

End point values	Part B: Evinacumab 15mg/Kg IV Q4W
Number of subjects analysed	14
Units: DayMilligrams per Liter (Daymg/L)
arithmetic mean (standard deviation)	7019 ( 2561 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose up to week 96 (24 weeks in Part A/B + 48 weeks of treatment in Part C + 24 weeks of follow-up)

Adverse event reporting additional description

Part A - up to week 24 Part B - up to Week 48 or up to the day before the first dose in Part C for participants entering Part C Part C - up to a 48-week treatment period and 24-week follow-up

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Part A Evinacumab 15mg

Reporting group description

Participants received single intravenous (IV) infusion of evinacumab at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 in Part A.

Reporting group title

Part B-C Evinacumab 15mg

Reporting group description

All participants who completed Part B received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Reporting group title

Part A-C Evinacumab 15mg

Reporting group description

All participants who completed Part A received IV infusion of evinacumab at a dose of 15 mg/kg Q4W from Day 1 up to Week 48 in Part C.

Reporting group title

Part B Evinacumab 15mg

Reporting group description

Participants received IV infusion of evinacumab at a dose of 15 mg/kg every four weeks (Q4W) from Day 1 up to Week 24 in Part B.

Serious adverse events	Part A Evinacumab 15mg	Part B-C Evinacumab 15mg	Part A-C Evinacumab 15mg	Part B Evinacumab 15mg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 14 (7.14%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Cardiac disorders
Aortic valve stenosis
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Tonsillitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A Evinacumab 15mg	Part B-C Evinacumab 15mg	Part A-C Evinacumab 15mg	Part B Evinacumab 15mg
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 6 (83.33%)	11 / 14 (78.57%)	6 / 6 (100.00%)	11 / 14 (78.57%)
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Hypertension
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	1 / 14 (7.14%)
occurrences all number	0	1	2	1
Pyrexia
subjects affected / exposed	0 / 6 (0.00%)	4 / 14 (28.57%)	2 / 6 (33.33%)	1 / 14 (7.14%)
occurrences all number	0	5	2	1
Chest pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	2	1	0
Infusion site extravasation
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0
Influenza like illness
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Infusion site swelling
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	2 / 6 (33.33%)	4 / 14 (28.57%)	1 / 6 (16.67%)	3 / 14 (21.43%)
occurrences all number	2	6	2	3
Cough
subjects affected / exposed	2 / 6 (33.33%)	2 / 14 (14.29%)	2 / 6 (33.33%)	1 / 14 (7.14%)
occurrences all number	2	3	2	3
Rhinitis allergic
subjects affected / exposed	2 / 6 (33.33%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	2	1	0	0
Dyspnoea
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	2	0	0
Product issues
Device malfunction
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	1	0	2	0
Investigations
Body temperature increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)
occurrences all number	0	0	1	1
Alanine aminotransferase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Vitamin D decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Lipoprotein (a) increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Apheresis related complication
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0
Fall
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Procedural pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Skin abrasion
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Burn oral cavity
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Limb injury
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Sunburn
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Thermal burn
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Cardiac disorders
Pericardial effusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 6 (16.67%)	4 / 14 (28.57%)	1 / 6 (16.67%)	2 / 14 (14.29%)
occurrences all number	1	7	1	3
Neuropathy peripheral
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Blood and lymphatic system disorders
Poikilocytosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Ear and labyrinth disorders
Deafness unilateral
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Ear pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	1	0	1
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Retinal thickening
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Papilloedema
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 6 (16.67%)	2 / 14 (14.29%)
occurrences all number	0	1	2	3
Abdominal pain
subjects affected / exposed	0 / 6 (0.00%)	3 / 14 (21.43%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	3	0	2
Abdominal discomfort
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	1
Vomiting
subjects affected / exposed	1 / 6 (16.67%)	3 / 14 (21.43%)	1 / 6 (16.67%)	2 / 14 (14.29%)
occurrences all number	1	3	2	2
Nausea
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	2 / 14 (14.29%)
occurrences all number	0	2	0	2
Diarrhoea
subjects affected / exposed	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 6 (0.00%)	2 / 14 (14.29%)
occurrences all number	0	3	0	2
Constipation
subjects affected / exposed	1 / 6 (16.67%)	2 / 14 (14.29%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	4	0	0
Toothache
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Dyspepsia
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Gastritis
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	1	0	1
Rash
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)
occurrences all number	0	0	1	2
Miliaria
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Proteinuria
subjects affected / exposed	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	3	0	0
Musculoskeletal and connective tissue disorders
Osteochondrosis
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Pain in extremity
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Gastrointestinal viral infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Oral herpes
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Otitis media
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	2	0	0
Rhinitis
subjects affected / exposed	1 / 6 (16.67%)	1 / 14 (7.14%)	2 / 6 (33.33%)	0 / 14 (0.00%)
occurrences all number	1	1	2	0
Tonsillitis
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
COVID-19
subjects affected / exposed	1 / 6 (16.67%)	10 / 14 (71.43%)	4 / 6 (66.67%)	1 / 14 (7.14%)
occurrences all number	1	10	4	1
Nasopharyngitis
subjects affected / exposed	1 / 6 (16.67%)	2 / 14 (14.29%)	0 / 6 (0.00%)	2 / 14 (14.29%)
occurrences all number	1	2	0	2
Upper respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1
Ear infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0
Pharyngitis
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0
Metabolism and nutrition disorders
Iron deficiency
subjects affected / exposed	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	1
Vitamin D deficiency
subjects affected / exposed	2 / 6 (33.33%)	0 / 14 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)
occurrences all number	2	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 May 2020

Study designed revised to reduce treatment periods of Parts B and C; Updated exclusion criteria; Added endpoint; Added information for Events that Require Expedited reporting to Sponsor; Other clarifications and editorial updates

25 May 2022

Amendment to allow participants who entered the compassionate use program or early access program to forgo the follow-up period of the study since the follow-up period was intended to be an off-drug follow-up period; Overall target and Part B populations reduced.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Three-Part, Single-Arm, Open-Label Study To Evaluate The Efficacy, Safety, And Pharmacokinetics Of Evinacumab In Pediatric Patients With Homozygous Familial Hypercholesterolemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab

Primary: Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab

Primary: Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab

Primary: Part A: Area Under the Serum Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab

Primary: Part A: Terminal Half-Life (t1/2) of Evinacumab

Primary: Part A: Terminal Half-Life (t1/2) of Evinacumab

Primary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24

Primary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24

Secondary: Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24

Secondary: Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24

Secondary: Part A and Part B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: Part A and Part B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24

Secondary: Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24

Secondary: Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24

Secondary: Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24

Secondary: Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24

Secondary: Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24

Secondary: Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24

Secondary: Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24

Secondary: Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24

Secondary: Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have Negative/Negative and Null/Null Mutations

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have Negative/Negative and Null/Null Mutations

Secondary: Part B: Serum Concentration of Total Evinacumab

Secondary: Part B: Serum Concentration of Total Evinacumab

Secondary: Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab

Secondary: Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have by null/null vs. non-null/null and negative/negative vs.non-negative/negative Mutations

Secondary: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24 in Participants who have by null/null vs. non-null/null and negative/negative vs.non-negative/negative Mutations

Secondary: Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab

Secondary: Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab

Secondary: Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab

Secondary: Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Three-Part, Single-Arm, Open-Label Study To Evaluate The Efficacy, Safety, And Pharmacokinetics Of Evinacumab In Pediatric Patients With Homozygous Familial Hypercholesterolemia