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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04233918




Registration number
NCT04233918
Ethics application status
Date submitted
6/01/2020
Date registered
18/01/2020
Date last updated
16/07/2024

Titles & IDs
Public title
Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
Scientific 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
Secondary ID [1] 0 0
2019-001931-30
Secondary ID [2] 0 0
R1500-CL-17100
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Homozygous Familial Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Evinacumab

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


Treatment: Drugs: Evinacumab
Part A: Single IV dose Part B \& C: IV dose Q4W
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab
Timepoint [1] 0 0
At day 12
Primary outcome [2] 0 0
Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab
Timepoint [2] 0 0
Up to Week 12
Primary outcome [3] 0 0
Part A: Terminal Half-Life (t1/2) of Evinacumab
Timepoint [3] 0 0
Up to week 12
Primary outcome [4] 0 0
Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Part A: up to Week 24; Part B: up to Week 48
Secondary outcome [2] 0 0
Part B: Percent Change in Apolipoprotein B (Apo B) From Baseline to Week 24
Timepoint [2] 0 0
Baseline to Week 24
Secondary outcome [3] 0 0
Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [5] 0 0
Part B: Percentage of Participants With =50 Percent (%) Reduction in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24
Timepoint [5] 0 0
Week 24
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline to Week 24
Secondary outcome [7] 0 0
Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24
Timepoint [7] 0 0
Baseline to Week 24
Secondary outcome [8] 0 0
Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Part B: Serum Concentration of Total Evinacumab
Timepoint [9] 0 0
Pre-dose at Weeks 0, 4, 8, 12; End of infusion at Weeks 0.006, 4.006, 8.006, 12.006 and 24
Secondary outcome [10] 0 0
Part B: Maximum Serum Concentration at Steady State (Cmax,ss) of Evinacumab
Timepoint [10] 0 0
Post-dose up to day 169
Secondary outcome [11] 0 0
Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab
Timepoint [11] 0 0
Post-dose up to day 169
Secondary outcome [12] 0 0
Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) of Evinacumab
Timepoint [12] 0 0
Post-dose up to day 169
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline to Week 24

Eligibility
Key inclusion criteria
Key

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
Minimum age
5 Years
Maximum age
11 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2023
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Regeneron Research Center - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Delaware
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
Austria
State/province [7] 0 0
Vienna
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Taiwan
State/province [9] 0 0
Taipei
Country [10] 0 0
Ukraine
State/province [10] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT04233918
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04233918