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

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04233918
• Collaborator: (none)
• Enrollment: 20
• Locations: 11
• Arm: 1
• Anticipated Duration (Months): 34.7
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Homozygous Familial Hypercholesterolemia	Drug: Evinacumab	Phase 3

Detailed Description

Part A is Phase 1b Part B is Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 29, 2020
• Actual Primary Completion Date: Jan 31, 2022
• Anticipated Study Completion Date: May 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Evinacumab Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W	Drug: Evinacumab; Part A: Single IV dose Part B & C: IV dose Q4W; Other Names: REGN1500 Evkeeza™

Outcome Measures

Primary Outcome Measures

1. PK parameter: Maximum serum concentration observed (Cmax) [Up to week 24]

   Part A

2. PK parameter: Area under the concentration-time curve (AUC) [Up to week 24]

   Part A

3. PK parameter: Observed terminal half-life linear (t1/2) [Up to week 24]

   Part A

4. Percent change in calculated low-density lipoprotein cholesterol (LDL-C) from baseline to week 24 [Week 24]

   Part B

Secondary Outcome Measures

1. Incidence of treatment-emergent adverse events (TEAE) and other safety variables over time [Up to week 44]

   Parts A & B; safety variables include laboratory data, vital signs, Tanner stages, and electrocardiograms (ECG).

2. Percent change in Apoliprotein (Apo) B from baseline to week 24 [Week 24]

   Part B

3. Percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24 [Week 24]

   Part B

4. Percent change in total cholesterol (TC) from baseline to week 24 [Week 24]

   Part B

5. Proportion of patients with ≥50% reduction in calculated LDL-C at week 24 [Week 24]

   Part B

6. Percent change in calculated LDL-C from baseline to week 24 in patients who have negative/negative and null/null mutations [Week 24]

   Part B

7. Percent change in lipoprotein a [Lp(a)] from baseline to week 24 [Week 24]

   Part B

8. Absolute change in LDL-C at week 24 [Week 24]

   Part B

9. Concentrations of total evinacumab over time [Up to week 44]

   Part B

10. PK parameter: Cmax steady state(Cmax.ss) [Up to week 44]

    Part B

11. PK parameter: Concentration of drug over time (the area under the concentration verses time curve over the dosing interval [AUCtau.ss[) [Up to week 44]

    Part B

12. PK parameter: Ctrough.ss [Up to week 44]

    Part B

13. Incidence and titer of treatment-emergent anti-drug antibodies (ADA) over time [Up to week 44]

    Part B

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol

2. LDL-C >130 mg/dL at the screening visit

3. Body weight ≥15 kg

4. Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.

5. Willing and able to comply with clinic visits and study-related procedures

6. 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:

1. 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

2. For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit

3. 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).

4. Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B

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

6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled diabetes as defined in the protocol

Note: Other protocol-defined criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regeneron Research Site	Wilmington	Delaware	United States	19803
2	Regeneron Research Site	Boca Raton	Florida	United States	33434
3	Regeneron Research Site	Kansas City	Kansas	United States	66190
4	Regeneron Research Center	Boston	Massachusetts	United States	02115
5	Regeneron Research Center	Philadelphia	Pennsylvania	United States	19106
6	Regeneron Research Center	Salt Lake City	Utah	United States	84108
7	Regeneron Research Center	Westmead	New South Wales	Australia	2145
8	Regeneron Research Site	Vienna		Austria	1090
9	Regeneron Research Site	Amsterdam		Netherlands	1105 AZ
10	Regeneron Research Center	Taipei		Taiwan	11217
11	Regeneron Research Site	Kyiv		Ukraine	04209

Sponsors and Collaborators

• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04233918
• Other Study ID Numbers: R1500-CL-17100; 2019-001931-30
• First Posted: Jan 18, 2020
• Last Update Posted: Feb 14, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Regeneron Pharmaceuticals: HoFH
• Additional relevant MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia

Study Results

No Results Posted as of Feb 14, 2022