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

NCT03452228 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: R1500-HTG-15222016-003307-62
• Study Type: interventional
• Target: 52
• Locations: 4 countries
• Sites: 17

Brief Summary

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

Conditions

Severe Hypertriglyceridemia (sHTG)

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants

  For participants randomized to evinacumab treatment group, baseline (Week 0) TG was defined as the geometric mean of all available TG results at day -28, day -14 and week 0; for participants randomized to placebo treatment group, baseline (Week 12) TG was defined as the geometric mean of all available TG results at weeks 6, 8, and 12.

  Participants randomized to evinacumab: Week 0 corresponds to Baseline and 12 weeks treatment corresponds to Week 12 of the DBTP; Participants randomized to placebo: Week 12 corresponds to Baseline and 12 weeks treatment corresponds to Week 24 of the SBTP

Secondary Outcomes (13)

• Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group

  DBTP: Baseline, Weeks 2, 4, 6, 8, 12; SBTP: Weeks 16, 20, and 24

• Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab in Actual Cohorts 1, 2, and 3

  Weeks 2, 4, 6, 8, 12, 16, 20, and 24

• Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS)

  Baseline, Week 12 (DBTP), Week 24 (SBTP)

• Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB)

  Baseline, Week 12 (DBTP), Week 24 (SBTP)

• DBTP: Change From Baseline in Degree of Pancreatic Injury/Inflammation Through 18F-2-Fluoro-2-Deoxy-D Glucose Positron Emission Tomography (18F-FDG-PET) Imaging Following 12 Weeks of Treatment With Evinacumab Assessed by 18F-FDG SUVmax and SUVmean

  Participants randomized to evinacumab: Week 0 corresponds to Baseline and 12 weeks treatment corresponds to Week 12 of the DBTP; Participants randomized to placebo: Week 12 corresponds to Baseline and 12 weeks treatment corresponds to Week 24 of the SBTP

Study Arms (2)

evinacumab

EXPERIMENTAL

Drug: evinacumab

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

evinacumab DRUG

Administered by Intravenous (IV)

Also known as: REGN1500

evinacumab

Placebo DRUG

Administered by Intravenous (IV)

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• History of a hospitalization and diagnosis of acute pancreatitis in the past 10 years
• 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
• Body mass index (BMI) of 18-40 kg/m2

You may not qualify if:

• A hospital or clinic discharge diagnosis of acute pancreatitis within 12 weeks of screening
• 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
• 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
• History of bleeding disorders, esophageal varices, heparin induced thrombocytopenia, or contraindications to receiving heparin (eg, allergic reaction to heparin)
• Previous treatment with Glybera® in the past 5 years or treatment with lomitapide or mipomersen in the past 6 months
• Pregnant or breast feeding women

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (17)

Regeneron Research Facility

Boca Raton, Florida, 33434, United States

Location

Regeneron Research Facility

Atlanta, Georgia, 30328, United States

Location

Regeneron Research Facility

Kansas City, Kansas, 66160, United States

Location

Regeneron Research Facility

New York, New York, 10029, United States

Location

Regeneron Research Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Regeneron Research Facility

Pittsburgh, Pennsylvania, 15261, United States

Location

Regeneron Research Facility

Dallas, Texas, 75390, United States

Location

Regeneron Research Facility

Houston, Texas, 77030, United States

Location

Regeneron Research Facility

Milwaukee, Wisconsin, 53226, United States

Location

Regeneron Research Facility

Chicoutimi, Quebec, G7H7K9, Canada

Location

Regeneron Research Facility

Québec, Quebec, G1V4W2, Canada

Location

Regeneron Research Facility

Napoli, Campania, 80131, Italy

Location

Regeneron Research Facility

Rome, 00161, Italy

Location

Regeneron Research Facility

Birmingham, B15 2TH, United Kingdom

Location

Regeneron Research Facility

London, NW3 2QG, United Kingdom

Location

Regeneron Research Facility

London, SE1 7EH, United Kingdom

Location

Regeneron Research Facility

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, Moriarty PM, Rubba P, Whitcomb DC, Banerjee P, Gewitz A, Gonzaga-Jauregui C, McGinniss J, Ponda MP, Pordy R, Zhao J, Rader DJ. Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nat Med. 2023 Mar;29(3):729-737. doi: 10.1038/s41591-023-02222-w. Epub 2023 Mar 6.

  PMID: 36879129 DERIVED

MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

evinacumab

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: March 2, 2018
• Study Start: June 7, 2018
• Primary Completion: December 17, 2019
• Study Completion: July 23, 2020
• Last Updated: February 16, 2023
• Results First Posted: February 16, 2023

Record last verified: 2023-01

Locations

CA (2); IT (2); US (9); GB (4)