HypertriglyceridemiaPhase 2NCT04863014
Efficacy and Safety of Evinacumab in Adult Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis
A Phase 2 study testing evinacumab in people with Hypertriglyceridemia, run by Regeneron Pharmaceuticals at 39 sites in 4 countries.
Trial summary
The primary objective of the study is to determine the proportion of patients with elevated triglycerides (TG), without familial chylomicronemia syndrome (FCS) due to loss of function (LoF) mutations in lipoprotein lipase (LPL), and a history of hypertriglyceridemia (HTG)-associated acute pancreatitis (AP) who… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertriglyceridemia
- What is being tested?
- evinacumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 39 sitesin 4 countries
- Study dates
- 12 Jul 2021to 15 Feb 2023
- Phase
- Phase 2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults without FCS due to LPL loss of function mutations
- Documented history of 1 HTG-associated AP episode within 24 months of screening
- Fasting serum TG value >880 mg/dL (10 mmol/L) or >500 mg/dL (5.6mmol/L) determined during the screening period as described in the protocol
- Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study
- Body mass index ≥18.0 and ≤45.0 kg/m2
- Compliance with a stable diet and exercise regimen at screening and willingness to continue the diet through the end of the study
Who cannot join
- Hospitalization for AP within 4 weeks of screening
- Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol
- Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol
- Use of any medication or nutraceutical known to alter serum lipids which has not been part of a stable therapeutic regimen for at least 8 weeks, and there are no plans to change the regimen during the study
- Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
- Has received a COVID-19 vaccination within 1-week of planned start medication or for which the planned COVID-19 vaccination would not be completed 1-week prior to start of the study
- Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Trial locations and contacts
39 sites in 4 countries.
39 sites in 4 countries
United States32 sites
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
Excel Medical Clinical Trials, LLC
Boca Raton, Florida, 33434
St. Vincent Medical Group, Inc.
Carmel, Indiana, 46290
Medical University of South Carolina
Charleston, South Carolina, 29425
University Diabetes & Endocrine Consultants
Chattanooga, Tennessee, 37411
University of Cincinnati Hospital
Cincinnati, Ohio, 45267
Methodist Dallas Medical Center
Dallas, Texas, 75208
NorthShore Medical Group
Evanston, Illinois, 60201
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Harmony Medical Research Institute, Inc.
Hialeah, Florida, 33015
University of Kansas Medical Center
Kansas City, Kansas, 66160
Sante Clinical Research
Kerrville, Texas, 78028
Northwell Health
Manhasset, New York, 11030
Wisconsin Center for Advanced Research - a division of GI Associates, LLC
Milwaukee, Wisconsin, 53215
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Minneapolis Heart Institute
Minneapolis, Minnesota, 55407
University of Minnesota
Minneapolis, Minnesota, 55422
West Virginia University Heart & Vascular Institute
Morgantown, West Virginia, 26506
Yale Cancer Center - Yale University
New Haven, Connecticut, 06510
Weill Cornell Medical College
New York, New York, 10021
Mt Sinai - Ichan Medical Institute
New York, New York, 10029
Radin Cardivascular Medical Group, Inc
Newport Beach, California, 92663
Advocate Medical Group Midwest Heart Specialists
Park Ridge, Illinois, 60068
Methodist Medical Center of Illiniois - UnityPoint Clinic
Peoria, Illinois, 61636
Penn Medicine: University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
University Of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Quincy Medical Group
Quincy, Illinois, 62301
University of Washington
Seattle, Washington, 98109
MultiCare Institute for Research
Spokane, Washington, 99202
Saint Louis University
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Canada3 sites
Centre Etudes Cliniques Ecogene-21
Chicoutimi, Quebec, G7H 7K9
Robarts Research Institute
London, Ontario, N6A 5B7
Clinique des maladies lipidiques de Quebec
Québec, G1V 4W2
Germany2 sites
University Hospital Carl Gustav Carus
Dresden, 01307
University Hospital of Leipzig
Leipzig, 04103
Netherlands2 sites
Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)
Amsterdam, 1105 AZ
Ziekenhuis Rijnstate
Arnhem, 6815 AD
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis
The primary objective of the study is to determine the proportion of patients with elevated triglycerides (TG), without familial chylomicronemia syndrome (FCS) due to loss of function (LoF) mutations in lipoprotein lipase (LPL), and a history of hypertriglyceridemia (HTG)-associated acute pancreatitis (AP) who experience a recurrent episode of AP after treatment with evinacumab versus placebo.
The secondary objectives of the study are:
- To determine the change in the standard lipid profile after therapy with evinacumab versus placebo
- To determine the changes in specialty lipoprotein parameters (ApoC3, ApoB48, ApoB100, and nuclear magnetic resonance [NMR] lipid profile) after therapy with evinacumab versus placebo
- To measure the number of AP episodes per patient
- To assess the safety and tolerability of evinacumab
- To assess the potential immunogenicity of evinacumab
- To assess the concentrations of total evinacumab and total angiopoietin-like 3 (ANGPTL3)
- Conditions
- Hypertriglyceridemia
- Being tested
- evinacumab, Placebo
- Keywords
- Severe Hypertriglyceridemia (HTG), Recurrent Acute Pancreatitis
- Medical subject headings
- Hypertriglyceridemia, Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
evinacumabDrug
Also called REGN1500, Evkeeza™
Intravenous infusion every 4 weeks (Q4W)
PlaceboOther
Intravenous infusion Q4W
| Study group | Role | What they receive |
|---|---|---|
| evinacumab | Experimental | Randomized 1:1 Receives: Drug: evinacumab |
| Placebo | Placebo comparator | Randomized 1:1 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode
All AP (Acute Pancreatitis) episodes occurred post-study drug treatment.
Measured: Baseline to 52 weeks
Secondary outcomes (17)
Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52
Apolipoproteins transport lipids through the body by binding with fat and cholesterol to form lipoproteins. ApoC3 was a component of very-low-density lipoproteins (VLDL), high-density lipoprotein (HDL), and triglyceride-rich chylomicrons and regulates lipid metabolism. Percent change in ApoC3 from Baseline to Week 52 was reported.
Measured: Baseline to week 52
Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)
Measured: Baseline to week 52
Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)
Measured: Baseline to week 52
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)
Measured: Baseline to week 52
Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52
Measured: Baseline to week 52
Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52
Measured: Baseline to week 52
Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52
Measured: Baseline to week 52
Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant
Measured: Up to 52 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Measured: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With TEAEs Based on Severity
AE was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. TEAEs are defined as AEs that developed or worsened during the treatment period. Severity of TEAEs was graded according to the following scale: Mild: Does not interfere in a significant manner with the participants normal functioning level, Moderate: Produces some impairment of functioning but is not hazardous to health and Severe: Produces significant impairment of functioning or incapacitation and is a definite hazard to the participants health.
Measured: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Clinical laboratory parameters included biochemistry, hematology and urinalysis. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.
Measured: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)
Treatment-Emergent ADA was defined as any positive post baseline assay response when baseline results were negative or missing. Treatment-Emergent ADA responses were further classified as: Persistent (a positive result in the ADA assay detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period [based on] nominal sampling time], with no ADA-negative results in-between, regardless of any missing samples); Indeterminate (a positive result in the ADA assay at the last collection time point only, regardless of any missing samples); Transient (not persistent/indeterminate, regardless of any missing samples). Number of participants with positive treatment-emergent ADA response during Week 52 were reported.
Measured: Baseline to Week 52
Number of Participants With Positive Neutralizing Antibodies (NAb)
NAb positive was defined as presence of at least one positive nAb sample.
Measured: Baseline to Week 52
Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
Percent Change in fasting HDL-C from Baseline to Week 52 was reported.
Measured: Baseline to Week 52
Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52
LDL-C levels were determined in beta-quantification with ultracentrifugation method. Percent change in fasting LDL-C from Baseline to Week 52 was reported.
Measured: Baseline to Week 52
Concentration of Total Evinacumab in Serum
Concentration of total evinacumab in serum by time at Pre-dose and End of Infusion were analyzed and reported.
Measured: Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52
Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum
Concentration of total ANGPTL3 in serum by time were analyzed and reported.
Measured: Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start12 Jul 2021
- Primary completion15 Feb 2023
- Study completion15 Feb 2023
Why it stopped: Sponsor Decision
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.
- Other trials for HypertriglyceridemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 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
- NCT04863014
- Sponsor's protocol ID
- R1500-HTG-20118
- Other IDs
- 2021-000437-13
- Status last verified
- May 2024
- First submitted
- 26 Apr 2021
- Last updated
- 22 May 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
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis
- ClinicalTrials.gov ID
- NCT04863014
- Acronym / sponsor ID
- R1500-HTG-20118
- Conditions
- Hypertriglyceridemia
- Keywords
- Severe Hypertriglyceridemia (HTG), Recurrent Acute Pancreatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 15 Feb 2023 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 28 Apr 2021 (actual)
- Results
- Posted 22 May 2024
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 of the study is to determine the proportion of patients with elevated triglycerides (TG), without familial chylomicronemia syndrome (FCS) due to loss of function (LoF) mutations in lipoprotein lipase (LPL), and a history of hypertriglyceridemia (HTG)-associated acute pancreatitis (AP) who experience a recurrent episode of AP after treatment with evinacumab versus placebo.
The secondary objectives of the study are:
- To determine the change in the standard lipid profile after therapy with evinacumab versus placebo
- To determine the changes in specialty lipoprotein parameters (ApoC3, ApoB48, ApoB100, and nuclear magnetic resonance [NMR] lipid profile) after therapy with evinacumab versus placebo
- To measure the number of AP episodes per patient
- To assess the safety and tolerability of evinacumab
- To assess the potential immunogenicity of evinacumab
- To assess the concentrations of total evinacumab and total angiopoietin-like 3 (ANGPTL3)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| evinacumab | Experimental | Drug: evinacumabRandomized 1:1 |
| Placebo | Placebo comparator | Other: PlaceboRandomized 1:1 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults without FCS due to LPL loss of function mutations
- Documented history of 1 HTG-associated AP episode within 24 months of screening
- Fasting serum TG value >880 mg/dL (10 mmol/L) or >500 mg/dL (5.6mmol/L) determined during the screening period as described in the protocol
- Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study
- Body mass index ≥18.0 and ≤45.0 kg/m2
Key exclusion criteria (7 listed)
- Hospitalization for AP within 4 weeks of screening
- Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol
- Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol
- Use of any medication or nutraceutical known to alter serum lipids which has not been part of a stable therapeutic regimen for at least 8 weeks, and there are no plans to change the regimen during the study
- Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
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™Intravenous infusion every 4 weeks (Q4W) | Drug | evinacumab |
| PlaceboIntravenous infusion Q4W | Other | Placebo |
Primary outcome
Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode
Time frame: Baseline to 52 weeks
All AP (Acute Pancreatitis) episodes occurred post-study drug treatment.
17 secondary outcomes
Percent Change in Apolipoprotein C3 (ApoC3) From Baseline to Week 52
Time frame: Baseline to week 52
Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)
Time frame: Baseline to week 52
Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)
Time frame: Baseline to week 52
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)
Time frame: Baseline to week 52
Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52
Time frame: Baseline to week 52
Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52
Time frame: Baseline to week 52
Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52
Time frame: Baseline to week 52
Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant
Time frame: Up to 52 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With TEAEs Based on Severity
Time frame: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Time frame: From start of study drug administration up to off drug follow-up (up to Week 72)
Number of Participants With Positive Treatment-emergent Anti-Drug Antibodies (ADA)
Time frame: Baseline to Week 52
Number of Participants With Positive Neutralizing Antibodies (NAb)
Time frame: Baseline to Week 52
Percent Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
Time frame: Baseline to Week 52
Percent Change in Fasting Low Density Lipoprotein (LDL-C) From Baseline to Week 52
Time frame: Baseline to Week 52
Concentration of Total Evinacumab in Serum
Time frame: Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52
Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum
Time frame: Pre-dose and End of Infusion (EOI) at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 36, 40, 44, and 48; Pre-dose at Weeks 28 and 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
39 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing evinacumab in people with Hypertriglyceridemia, run by Regeneron Pharmaceuticals at 39 sites in 4 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: stopped early, as of the sponsor's last update on 22 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Canada, Germany, Netherlands. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 22 May 2024). 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?
Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode (time frame: Baseline to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2024.