Clinical trial NCT04233918: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: HoFH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab
timeFrame: At day 12
measure: Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab
timeFrame: Up to Week 12
measure: Part A: Terminal Half-Life (t1/2) of Evinacumab
timeFrame: Up to week 12
measure: Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Part A: up to Week 24; Part B: up to Week 48
measure: Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Part B: Percentage of Participants With ≥50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24
timeFrame: Week 24
measure: 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
timeFrame: Baseline to Week 24
measure: Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Serum Concentration of Total Evinacumab
timeFrame: Pre-dose at Weeks 0, 4, 8, 12; End of infusion at Weeks 0.006, 4.006, 8.006, 12.006 and 24
measure: Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab
timeFrame: Post-dose up to day 169
measure: Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab
timeFrame: Post-dose up to day 169
measure: Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab
timeFrame: Post-dose up to day 169
measure: 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
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Regeneron Research Site
state: Delaware
city: Boca Raton
country: United States
facility: Regeneron Research Site
state: Florida
city: Kansas City
country: United States
facility: Regeneron Research Site
state: Kansas
city: Boston
country: United States
facility: Regeneron Research Center
state: Massachusetts
city: Philadelphia
country: United States
facility: Regeneron Research Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Regeneron Research Center
state: Utah
city: Westmead
country: Australia
facility: Regeneron Research Center
state: New South Wales
city: Vienna
country: Austria
facility: Regeneron Research Site
city: Amsterdam
country: Netherlands
facility: Regeneron Research Site
city: Taipei
country: Taiwan
facility: Regeneron Research Center
city: Kyiv
country: Ukraine
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: