Safety and Efficacy Following Repeat-Dose of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute Pancreatitis

• ClinicalTrials.gov Identifier: NCT03452228
• Recruitment Status: Completed
• First Posted: March 2, 2018
• Last Update Posted: December 24, 2020
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

The primary objective is to determine the change in Triglyceride (TG) levels following 12 weeks of repeated Intravenous (IV) doses of evinacumab.

Condition or disease	Intervention/treatment	Phase
Severe Hypertriglyceridemia (sHTG)	Drug: evinacumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Placebo-Controlled Study of Safety and Efficacy, Following Repeat-Dose Administration of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute Pancreatitis
• Actual Study Start Date: June 7, 2018
• Actual Primary Completion Date: December 17, 2019
• Actual Study Completion Date: July 23, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: evinacumab	Drug: evinacumab; Administered by Intravenous (IV); Other Name: REGN1500
Experimental: Placebo	Drug: Placebo; Administered by Intravenous (IV)

Outcome Measures

Primary Outcome Measures :

1. Percent lowering of TG levels from baseline following 12 weeks of repeated IV doses of evinacumab [ Time Frame: Week 12 ]

Secondary Outcome Measures :

1. Percent TG lowering from baseline following 2 to 24 weeks of repeated IV doses of evinacumab [ Time Frame: Up to 24 weeks ]
2. Changes in patient reported abdominal and GI daily symptom questionnaire [ Time Frame: Up to 48 weeks ]
3. Changes in patient reported daily dietary habits and impact questionnaire [ Time Frame: Up to 48 weeks ]
4. Degree of pancreatic injury/inflammation through 18F-2-Fluoro-2-Deoxy-D glucose positron emission tomography (18F-FDG-PET) imaging at baseline as assessed by 18F-FDG standardized uptake values SUVmax and SUVmean [ Time Frame: Baseline ]
5. Change from baseline to degree of pancreatic injury/inflammation through 18F-FDG-PET imaging following 12 weeks of treatment with evinacumab as assessed by 18F-FDG standardized uptake values SUVmax and SUVmean [ Time Frame: Week 12 ]
6. Degree of pancreatic injury/inflammation through Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) at baseline as assessed by ADC [ Time Frame: Baseline ]
7. Change from baseline to degree of pancreatic injury/inflammation through DW-MRI following 12 weeks of treatment with evinacumab as assessed by ADC [ Time Frame: Week 12 ]
8. Change from baseline to degree of pancreatic injury/inflammation through DW-MRI following 24 weeks of treatment with evinacumab as assessed by ADC [ Time Frame: Week 24 ]
9. Total evinacumab concentration in serum [ Time Frame: Up to 48 weeks ]
10. Total ANGPTL3 concentrations [ Time Frame: Up to 48 weeks ]
11. Incidence of anti-drug antibody (ADA) [ Time Frame: Up to 48 weeks ]
12. Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 48 weeks ]
13. Incidence of serious adverse events (SAEs) [ Time Frame: Up to 48 weeks ]
14. Incidence of laboratory abnormalities [ Time Frame: Up to 48 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Previous documentation in the patient's medical records of a fasting serum TG measurement ≥ 1000 mg/dL (11.3 mmol/L) on more than 1 occasion, and all fasting TG values ≥500 mg/dL (5.6 mmol/L) at screening
2. History of a hospitalization and diagnosis of acute pancreatitis in the past 10 years
3. On stable lipid-modifying diet with or without medications (eg, statins, niacin, omega-3 fatty acids). Lipid-modifying diet and doses of medications should be stable for at least 4 weeks (6 weeks for fibrates, 8 weeks for PCSK9 inhibitors) prior to screening
4. Body mass index (BMI) of 18-40 kg/m2

Key Exclusion Criteria:

1. A hospital or clinic discharge diagnosis of acute pancreatitis within 12 weeks of screening
2. Lipid apheresis or plasma exchange treatment within the last 4 weeks or plans to undergo apheresis or plasma exchange during the time frame of the study
3. History of class 3/4 heart failure at any time in the past, or hospitalization for heart failure, diagnosis of a myocardial infarction, stroke, Transient ischemic attack (TIA), unstable angina, Coronary artery bypass surgery (CABG), Percutaneous coronary intervention (PCI), carotid surgery/stenting within 3 months before the screening visit
4. History of bleeding disorders, esophageal varices, heparin induced thrombocytopenia, or contraindications to receiving heparin (eg, allergic reaction to heparin)
5. Previous treatment with Glybera® in the past 5 years or treatment with lomitapide or mipomersen in the past 6 months
6. Pregnant or breast feeding women

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

United States, Florida

Regeneron Research Facility

Boca Raton, Florida, United States, 33434

United States, Georgia

Regeneron Research Facility

Atlanta, Georgia, United States, 30328

United States, Kansas

Regeneron Research Facility

Kansas City, Kansas, United States, 66160

United States, New York

Regeneron Research Facility

New York, New York, United States, 10029

United States, Pennsylvania

Regeneron Research Facility

Philadelphia, Pennsylvania, United States, 19104

Regeneron Research Facility

Pittsburgh, Pennsylvania, United States, 15261

United States, Texas

Regeneron Research Facility

Dallas, Texas, United States, 75390

Regeneron Research Facility

Houston, Texas, United States, 77030

United States, Wisconsin

Regeneron Research Facility

Milwaukee, Wisconsin, United States, 53226

Canada, Quebec

Regeneron Research Facility

Chicoutimi, Quebec, Canada, G7H7K9

Regeneron Research Facility

Québec, Quebec, Canada, G1V4W2

Italy

Regeneron Research Facility

Napoli, Campania, Italy, 80131

Regeneron Research Facility

Rome, Italy, 00161

United Kingdom

Regeneron Research Facility

Birmingham, United Kingdom, B15 2TH

Regeneron Research Facility

London, United Kingdom, NW3 2QG

Regeneron Research Facility

London, United Kingdom, SE1 7EH

Regeneron Research Facility

Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03452228
• Other Study ID Numbers: R1500-HTG-1522; 2016-003307-62 ( EudraCT Number )
• First Posted: March 2, 2018
• Last Update Posted: December 24, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pancreatitis; Hypertriglyceridemia; Pancreatic Diseases; Digestive System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases