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: Recruiting
• First Posted: March 2, 2018
• Last Update Posted: June 4, 2019
• 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)
• Estimated Enrollment: 50 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
• Estimated Primary Completion Date: May 18, 2020
• Estimated Study Completion Date: January 28, 2021

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

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, Colorado

Regeneron Research Facility; Recruiting

Aurora, Colorado, United States, 80045

United States, Florida

Regeneron Research Facility; Recruiting

Boca Raton, Florida, United States, 33434

United States, Georgia

Regeneron Research Facility; Recruiting

Atlanta, Georgia, United States, 30328

United States, Kansas

Regeneron Research Facility; Recruiting

Kansas City, Kansas, United States, 66160

United States, New York

Regeneron Research Facility; Recruiting

New York, New York, United States, 10029

United States, Pennsylvania

Regeneron Research Facility; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Regeneron Research Facility; Recruiting

Pittsburgh, Pennsylvania, United States, 15261

United States, Texas

Regeneron Research Facility; Recruiting

Dallas, Texas, United States, 75390

Regeneron Research Facility; Recruiting

Houston, Texas, United States, 77030

United States, Wisconsin

Regeneron Research Facility; Recruiting

Milwaukee, Wisconsin, United States, 53226

Canada, Quebec

Regeneron Research Facility; Recruiting

Chicoutimi, Quebec, Canada, G7H7K9

Regeneron Research Facility; Recruiting

Québec, Quebec, Canada, G1V4W2

Italy

Regeneron Research Facility; Recruiting

Napoli, Campania, Italy, 80131

Regeneron Research Facility; Recruiting

Rome, Italy, 00161

United Kingdom

Regeneron Research Facility; Recruiting

Birmingham, United Kingdom, B15 2TH

Regeneron Research Facility; Recruiting

London, United Kingdom, NW3 2QG

Regeneron Research Facility; Recruiting

London, United Kingdom, SE1 7EH

Regeneron Research Facility; Recruiting

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 History of Changes
• Other Study ID Numbers: R1500-HTG-1522; 2016-003307-62 ( EudraCT Number )
• First Posted: March 2, 2018
• Last Update Posted: June 4, 2019
• Last Verified: May 2019

• 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; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs