Efficacy and Safety of Evinacumab in Adult Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis

Hypertriglyceridemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04863014
• Other study ID #: R1500-HTG-20118
• Secondary ID: 2021-000437-13
• Status: Terminated
• Phase: Phase 2
• Start date: July 12, 2021
• Est. completion date: February 15, 2023

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: February 15, 2023
• Est. primary completion date: February 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key Inclusion Criteria:

1. Adults without FCS due to LPL loss of function mutations

2. Documented history of 1 HTG-associated AP episode within 24 months of screening

3. 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

4. Stable dose of lipid-lowering therapy (=8 weeks) and willingness to maintain a stable regimen throughout the study

5. Body mass index =18.0 and =45.0 kg/m2

6. Compliance with a stable diet and exercise regimen at screening and willingness to continue the diet through the end of the study

Key Exclusion Criteria:

1. Hospitalization for AP within 4 weeks of screening

2. Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol

3. Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol

4. 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

5. Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol

6. 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

Related Conditions & MeSH terms

• Hypertriglyceridemia
• Pancreatitis

Intervention

Drug:
• evinacumab
Intravenous infusion every 4 weeks (Q4W)

Other:
• Placebo
Intravenous infusion Q4W

Locations

Country	Name	City	State
Canada	Centre Etudes Cliniques Ecogene-21	Chicoutimi	Quebec
Canada	Robarts Research Institute	London	Ontario
Canada	Clinique des maladies lipidiques de Quebec	Quebec
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	University Hospital of Leipzig	Leipzig
Netherlands	Amsterdam University Medical Center (Amsterdam UMC), Academic Medical Center (AMC)	Amsterdam
Netherlands	Ziekenhuis Rijnstate	Arnhem
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	St. Vincent Medical Group, Inc.	Carmel	Indiana
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	University of Cincinnati Hospital	Cincinnati	Ohio
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	NorthShore Medical Group	Evanston	Illinois
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Harmony Medical Research Institute, Inc.	Hialeah	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Sante Clinical Research	Kerrville	Texas
United States	Northwell Health	Manhasset	New York
United States	Wisconsin Center for Advanced Research - a division of GI Associates, LLC	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Heart & Vascular Institute	Morgantown	West Virginia
United States	Yale Cancer Center - Yale University	New Haven	Connecticut
United States	Mt Sinai - Ichan Medical Institute	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Radin Cardivascular Medical Group, Inc	Newport Beach	California
United States	Advocate Medical Group Midwest Heart Specialists	Park Ridge	Illinois
United States	Methodist Medical Center of Illiniois - UnityPoint Clinic	Peoria	Illinois
United States	Penn Medicine: University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	University Of Pittsburgh	Pittsburgh	Pennsylvania
United States	Quincy Medical Group	Quincy	Illinois
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington
United States	MultiCare Institute for Research	Spokane	Washington
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With at Least One Positively Adjudicated Acute Pancreatitis (AP) Episode	All AP (Acute Pancreatitis) episodes occurred post-study drug treatment.	Baseline to 52 weeks
Secondary	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.	Baseline to week 52
Secondary	Percent Change in Fasting Triglycerides (TGs) - (From Baseline to Week 52)		Baseline to week 52
Secondary	Percent Change in Total Cholesterol (TC) - (Baseline to Week 52)		Baseline to week 52
Secondary	Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) - (From Baseline to Week 52)		Baseline to week 52
Secondary	Percent Change in Apolipoprotein B48 (ApoB48) From Baseline to Week 52		Baseline to week 52
Secondary	Percent Change in Apolipoprotein B100 (ApoB100) Levels From Baseline to Week 52		Baseline to week 52
Secondary	Percent Change in Nuclear Magnetic Resonance (NMR)-Determined Particle Size and Number From Baseline to Week 52		Baseline to week 52
Secondary	Number of Independently Adjudicated Positive Episodes of Acute Pancreatitis (AP) Per Participant		Up to 52 weeks
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs		From start of study drug administration up to off drug follow-up (up to Week 72)
Secondary	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.	From start of study drug administration up to off drug follow-up (up to Week 72)
Secondary	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.	From start of study drug administration up to off drug follow-up (up to Week 72)
Secondary	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.	Baseline to Week 52
Secondary	Number of Participants With Positive Neutralizing Antibodies (NAb)	NAb positive was defined as presence of at least one positive nAb sample.	Baseline to Week 52
Secondary	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.	Baseline to Week 52
Secondary	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.	Baseline to Week 52
Secondary	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.	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
Secondary	Concentration of Total Angiopoietin-like 3 (ANGPTL3) in Serum	Concentration of total ANGPTL3 in serum by time were analyzed and reported.	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