Homozygous Familial HypercholesterolemiaPhase 3NCT04233918
Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
A Phase 3 study testing Evinacumab in people with Homozygous Familial Hypercholesterolemia, run by Regeneron Pharmaceuticals at 11 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 11 years
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- Evinacumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 29 Jun 2020to 30 May 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
- LDL-C >130 mg/dL at the screening visit
- Body weight ≥15 kg
- Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.
- Willing and able to comply with clinic visits and study-related procedures
- 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)
Who cannot join
- 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
- For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
- 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).
- Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
- Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- 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
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
United States6 sites
Regeneron Research Site
Boca Raton, Florida, 33434
Regeneron Research Center
Boston, Massachusetts, 02115
Regeneron Research Site
Kansas City, Kansas, 66190
Regeneron Research Center
Philadelphia, Pennsylvania, 19106
Regeneron Research Center
Salt Lake City, Utah, 84108
Regeneron Research Site
Wilmington, Delaware, 19803
About this study
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
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.
Read more
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
Read the detailed description
Part A is Phase 1b Part B is Phase 3
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- Evinacumab
- Keywords
- HoFH
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvinacumabDrug
Also called REGN1500, Evkeeza™
Part A: Single IV dose Part B \& C: IV dose Q4W
| Study group | Role | What they receive |
|---|---|---|
| Evinacumab | Experimental | Part A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W Receives: Drug: Evinacumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab
Cmax was obtained directly from the plasma concentration versus time curve.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 24
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start29 Jun 2020
- Primary completion31 Jan 2022
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04233918
- Sponsor's protocol ID
- R1500-CL-17100
- Other IDs
- 2019-001931-30, 2019
- Status last verified
- Jun 2024
- First submitted
- 6 Jan 2020
- Last updated
- 16 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Publications
Wiegman A, Greber-Platzer S, Ali S, Reijman MD, Brinton EA, Charng MJ, Srinivasan S, Baker-Smith C, Baum S, Brothers JA, Hartz J, Moriarty PM, Mendell J, Bihorel S, Banerjee P, George RT, Hirshberg B, Pordy R. Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia. Circulation. 2024 Jan 30;149(5):343-353. doi: 10.1161/CIRCULATIONAHA.123.065529. Epub 2023 Oct 20.
PubMed 37860863
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04233918
- Acronym / sponsor ID
- R1500-CL-17100
- Conditions
- Homozygous Familial Hypercholesterolemia
- Keywords
- HoFH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2020 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Posted 7 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evinacumab | Experimental | Drug: EvinacumabPart A: Single intravenous (IV) dose Part B: IV dose every 4 weeks (Q4W) until week 20 Part C: IV dose Q4W |
Who may qualify
- Ages
- 5 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
- LDL-C >130 mg/dL at the screening visit
- Body weight ≥15 kg
- Receiving stable maximally tolerated therapy*at the screening visit *Maximally tolerated therapy could include a daily statin.
- Willing and able to comply with clinic visits and study-related procedures
Key exclusion criteria (7 listed)
- 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
- For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
- 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).
- Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
- Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvinacumabAlso: REGN1500, Evkeeza™Part A: Single IV dose Part B \& C: IV dose Q4W | Drug | Evinacumab |
Primary outcome
Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab
Time frame: At day 12
Cmax was obtained directly from the plasma concentration versus time curve.
Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Evinacumab
Time frame: Up to Week 12
AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.
Part A: Terminal Half-Life (t1/2) of Evinacumab
Time frame: Up to week 12
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.
Part B: Percent Change in Calculated Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 24
Time frame: 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.
13 secondary outcomes
Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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
Time frame: Baseline to Week 24
Part B: Percent Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 24
Time frame: Baseline to Week 24
Part B: Percent Change in Total Cholesterol (TC) From Baseline to Week 24
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
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
Time frame: Baseline to Week 24
Part B: Percent Change in Lipoprotein A (Lp[a]) From Baseline to Week 24
Time frame: Baseline to Week 24
Part B: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Week 24
Time frame: Baseline, Week 24
Part B: Serum Concentration of Total Evinacumab
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
Time frame: Post-dose up to day 169
Part B: Area Under the Serum Concentration-time Curve at Steady State (AUCtau.ss) of Evinacumab
Time frame: Post-dose up to day 169
Part B: Minimum Serum Concentration at Steady State (Ctrough.ss) 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37860863Wiegman A, Greber-Platzer S, Ali S, Reijman MD, Brinton EA, Charng MJ, Srinivasan S, Baker-Smith C, Baum S, Brothers JA, Hartz J, Moriarty PM, Mendell J, Bihorel S, Banerjee P, George RT, Hirshberg B, Pordy R. Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia. Circulation. 2024 Jan 30;149(5):343-353. doi: 10.1161/CIRCULATIONAHA.123.065529. Epub 2023 Oct 20.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Evinacumab in people with Homozygous Familial Hypercholesterolemia, run by Regeneron Pharmaceuticals at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Australia, Austria, Netherlands, Taiwan and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Maximum Observed Serum Concentration (Cmax) of Evinacumab (time frame: At day 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04233918, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2024.