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

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ClinicalTrials.gov Identifier: NCT04233918
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 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
Estimated Study Start Date : June 5, 2020
Estimated Primary Completion Date : December 16, 2022
Estimated Study Completion Date : January 27, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Evinacumab
Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 44 Part C: IV dose Q4W in the long-term extension
Drug: Evinacumab
Part A: Single IV dose Part B & C: IV dose Q4W
Other Name: REGN1500




Primary Outcome Measures :
  1. PK parameter: Maximum serum concentration observed (Cmax) [ Time Frame: Up to week 24 ]
    Part A

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

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

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


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAE) and other safety variables over time [ Time Frame: Up to week 68 ]
    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 [ Time Frame: Week 24 ]
    Part B

  3. Percent change in non-High-density lipoprotein cholesterol (HDL-C) from baseline to week 24 [ Time Frame: Week 24 ]
    Part B

  4. Percent change in total cholesterol (TC) from baseline to week 24 [ Time Frame: Week 24 ]
    Part B

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

  7. Percent change in lipoprotein a [Lp(a)] from baseline to week 24 [ Time Frame: Week 24 ]
    Part B

  8. Concentrations of total evinacumab over time [ Time Frame: Up to week 68 ]
    Part B

  9. PK parameter: Cmax steady state(Cmax.ss) [ Time Frame: Up to week 68 ]
    Part B

  10. PK parameter: Concentration of drug over time (the area under the concentration verses time curve over the dosing interval [AUCtau.ss[) [ Time Frame: Up to week 68 ]
    Part B

  11. PK parameter: Ctrough.ss [ Time Frame: Up to week 68 ]
    Part B

  12. Incidence and titer of treatment-emergent anti-drug antibodies (ADA) over time [ Time Frame: Up to week 68 ]
    Part B



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Provide signed informed consent or assent

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 the 48-week open-label treatment period
  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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04233918


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04233918    
Other Study ID Numbers: R1500-CL-17100
2019-001931-30 ( EudraCT Number )
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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.
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).
URL: https://errs.regeneron.com/external

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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:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias