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Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Evinacumab

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia focused on measuring HoFH

Eligibility Criteria

5 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
LDL-C >130 mg/dL at the screening visit
Body weight ≥15 kg
Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.
Willing and able to comply with clinic visits and study-related procedures
Parent(s) or legal guardian(s) must provide the signed informed consent form (ICF). Patients ≥5 years of age (or above age determined by the IRB/EC and in accordance with the local regulations and requirements) must also provide informed assent forms (IAFs) to enroll in the study, and sign and date a separate IAF or ICF signed by the parent(s)/legal guardian(s) (as appropriate based on local regulations and requirements)

Key Exclusion Criteria:

Background pharmacologic LMT, nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8 weeks for PCSK9 inhibitors) before the screening visit and patient is unwilling to enter the run-in period
For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
Receiving lipid apheresis, a setting (if applicable) and schedule that has not been stable for approximately 8 weeks before the screening visit or an apheresis schedule that is not anticipated to be stable over the duration of the treatment period (48 weeks).
Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled diabetes as defined in the protocol

Note: Other protocol-defined criteria apply

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Evinacumab

Arm Description

Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W

Outcomes

Primary Outcome Measures

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

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

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

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

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

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.

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

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.

Secondary Outcome Measures

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

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.

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

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

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

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

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

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

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

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

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

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.

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

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

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

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

Part B: Serum Concentration of Total Evinacumab

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

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

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

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

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

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

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

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

Full Information

NCT ID

NCT04233918

First Posted

January 6, 2020

Last Updated

June 5, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04233918

Brief Title

Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

Official Title

A Three-Part, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

June 29, 2020 (Actual)

Primary Completion Date

January 31, 2022 (Actual)

Study Completion Date

May 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective for Part A of the study is to assess the pharmacokinetics (PK) of evinacumab in pediatric patients 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) patients with HoFH. The secondary objective for Part A of the study is to evaluate the safety and tolerability of evinacumab administered intravenous (IV) in pediatric patients with HoFH. The secondary objectives for Part B of the study are: To evaluate the effect of evinacumab on other lipid parameters (ie, apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein a [Lp(a)]) in pediatric patients with HoFH To evaluate the safety and tolerability of evinacumab administered IV in pediatric patients with HoFH To assess the PK of evinacumab in pediatric patients with HoFH To assess the immunogenicity of evinacumab in pediatric patients with HoFH over time To evaluate patient efficacy by mutation status

Detailed Description

Part A is Phase 1b Part B is Phase 3

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Homozygous Familial Hypercholesterolemia

Keywords

HoFH

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Evinacumab

Arm Type

Experimental

Arm Description

Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W

Intervention Type

Drug

Intervention Name(s)

Evinacumab

Other Intervention Name(s)

REGN1500, Evkeeza™

Intervention Description

Part A: Single IV dose Part B & C: IV dose Q4W

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

At day 12

Title

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

Description

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

Time Frame

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

Title

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

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.

Time Frame

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

Title

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

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.

Time Frame

Baseline to Week 24

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

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

Time Frame

Baseline to Week 24

Title

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

Description

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

Time Frame

Baseline to Week 24

Title

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

Description

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

Time Frame

Baseline to Week 24

Title

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

Description

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

Time Frame

Week 24

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

Description

Time Frame

Baseline to Week 24

Title

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

Description

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

Time Frame

Baseline to Week 24

Title

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

Description

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

Time Frame

Baseline, Week 24

Title

Part B: Serum Concentration of Total Evinacumab

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.

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

Time Frame

Baseline to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

11 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol LDL-C >130 mg/dL at the screening visit Body weight ≥15 kg Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin. Willing and able to comply with clinic visits and study-related procedures Parent(s) or legal guardian(s) must provide the signed informed consent form (ICF). Patients ≥5 years of age (or above age determined by the IRB/EC and in accordance with the local regulations and requirements) must also provide informed assent forms (IAFs) to enroll in the study, and sign and date a separate IAF or ICF signed by the parent(s)/legal guardian(s) (as appropriate based on local regulations and requirements) Key Exclusion Criteria: Background pharmacologic LMT, nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8 weeks for PCSK9 inhibitors) before the screening visit and patient is unwilling to enter the run-in period For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit Receiving lipid apheresis, a setting (if applicable) and schedule that has not been stable for approximately 8 weeks before the screening visit or an apheresis schedule that is not anticipated to be stable over the duration of the treatment period (48 weeks). Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled diabetes as defined in the protocol Note: Other protocol-defined criteria apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Regeneron Research Site

City

Wilmington

State/Province

Delaware

ZIP/Postal Code

19803

Country

United States

Facility Name

Regeneron Research Site

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33434

Country

United States

Facility Name

Regeneron Research Site

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66190

Country

United States

Facility Name

Regeneron Research Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Regeneron Research Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19106

Country

United States

Facility Name

Regeneron Research Center

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84108

Country

United States

Facility Name

Regeneron Research Center

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Regeneron Research Site

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

Regeneron Research Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Regeneron Research Center

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

Regeneron Research Site

City

Kyiv

ZIP/Postal Code

04209

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.

IPD Sharing Access Criteria

Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency [EMA], Pharmaceuticals and Medical Devices Agency [PMDA], etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).

IPD Sharing URL

https://vivli.org/

Learn more about this trial

Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

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Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia

Homozygous Familial Hypercholesterolemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial