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

Regeneron Pharmaceuticals20 enrolled

Overview

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

Part A is Phase 1b Part B is Phase 3

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Homozygous Familial Hypercholesterolemia

Eligibility

Sex: ALLMin age: 5 YearsMax age: 11 Years

Medical Language ↔ Plain English

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

Locations (11)

Regeneron Research Site

Wilmington, Delaware, United States

Regeneron Research Site

Boca Raton, Florida, United States

Regeneron Research Site

Kansas City, Kansas, United States

Regeneron Research Center

Boston, Massachusetts, United States

Regeneron Research Center

Philadelphia, Pennsylvania, United States

Regeneron Research Center

Salt Lake City, Utah, United States

Regeneron Research Center

Westmead, New South Wales, Australia

Regeneron Research Site

Vienna, Austria

Regeneron Research Site

Amsterdam, Netherlands

Regeneron Research Center

Taipei, Taiwan

...and 1 more locations

Outcomes

Primary Outcomes

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

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

Time frame: At day 12

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.

Time frame: Up to Week 12

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.

Time frame: Up to week 12

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.

Time frame: Baseline to Week 24

Secondary Outcomes

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. 1 participant experienced an AE during part B that was recorded after Part B database lock. This was not reflected in the reported endpoint number of participants of 10.

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

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.

Time frame: Baseline to Week 24

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.

Time frame: Baseline to Week 24

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

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

Time frame: Baseline to Week 24

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.

Time frame: Week 24

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.

Time frame: Baseline to Week 24

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.

Time frame: Baseline to Week 24

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

Time frame: Baseline, Week 24

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.

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

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

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

Time frame: Post-dose up to day 169

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

Time frame: Post-dose up to day 169

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

Time frame: Post-dose up to day 169

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

Time frame: Baseline to Week 24

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

Overview

Conditions

Interventions

Eligibility

Locations (11)

Outcomes

Primary Outcomes

Secondary Outcomes