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

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03452228
Collaborator
(none)
52
Enrollment
17
Locations
2
Arms
25.5
Actual Duration (Months)
3.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
Phase 2

Study Design

Study Type:
Interventional
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 :
Jun 7, 2018
Actual Primary Completion Date :
Dec 17, 2019
Actual Study Completion Date :
Jul 23, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: evinacumab

Drug: evinacumab
Administered by Intravenous (IV)
Other Names:
  • 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 [Week 12]

    Secondary Outcome Measures

    1. Percent TG lowering from baseline following 2 to 24 weeks of repeated IV doses of evinacumab [Up to 24 weeks]

    2. Changes in patient reported abdominal and GI daily symptom questionnaire [Up to 48 weeks]

    3. Changes in patient reported daily dietary habits and impact questionnaire [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 [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 [Week 12]

    6. Degree of pancreatic injury/inflammation through Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) at baseline as assessed by ADC [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 [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 [Week 24]

    9. Total evinacumab concentration in serum [Up to 48 weeks]

    10. Total ANGPTL3 concentrations [Up to 48 weeks]

    11. Incidence of anti-drug antibody (ADA) [Up to 48 weeks]

    12. Incidence of Treatment-emergent adverse events (TEAEs) [Up to 48 weeks]

    13. Incidence of serious adverse events (SAEs) [Up to 48 weeks]

    14. Incidence of laboratory abnormalities [Up to 48 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Site City State Country Postal Code
    1 Regeneron Research Facility Boca Raton Florida United States 33434
    2 Regeneron Research Facility Atlanta Georgia United States 30328
    3 Regeneron Research Facility Kansas City Kansas United States 66160
    4 Regeneron Research Facility New York New York United States 10029
    5 Regeneron Research Facility Philadelphia Pennsylvania United States 19104
    6 Regeneron Research Facility Pittsburgh Pennsylvania United States 15261
    7 Regeneron Research Facility Dallas Texas United States 75390
    8 Regeneron Research Facility Houston Texas United States 77030
    9 Regeneron Research Facility Milwaukee Wisconsin United States 53226
    10 Regeneron Research Facility Chicoutimi Quebec Canada G7H7K9
    11 Regeneron Research Facility Québec Quebec Canada G1V4W2
    12 Regeneron Research Facility Napoli Campania Italy 80131
    13 Regeneron Research Facility Rome Italy 00161
    14 Regeneron Research Facility Birmingham United Kingdom B15 2TH
    15 Regeneron Research Facility London United Kingdom NW3 2QG
    16 Regeneron Research Facility London United Kingdom SE1 7EH
    17 Regeneron Research Facility Manchester United Kingdom M13 9WL

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03452228
    Other Study ID Numbers:
    • R1500-HTG-1522
    • 2016-003307-62
    First Posted:
    Mar 2, 2018
    Last Update Posted:
    Dec 24, 2020
    Last Verified:
    Dec 1, 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

    Study Results

    No Results Posted as of Dec 24, 2020