Phase 2
N=52
Safety and Efficacy Following Repeat-Dose of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute Pancreatitis
Severe Hypertriglyceridemia (sHTG)
Bottom Line
View on ClinicalTrials.gov: NCT03452228 ↗Enrolled (actual)
52
Serious AEs
22.5%
Results posted
Feb 2023
Primary outcome: Primary: Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants — 19.2; -37.2 Percent Change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- evinacumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants |
19.2; -37.2 | — |
| SECONDARY Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group |
1.99; -51.38; -3.52; -43.70; 92.56; -52.69 | — |
| SECONDARY 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 |
-28.3; -77.5; -74.4; -19.0; -48.0; -70.3 | — |
| SECONDARY Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS) |
-0.69; -0.74; -0.12 | — |
| SECONDARY Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) |
-2.267; 2.021; -1.255 | — |
| SECONDARY 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 |
2.318; 2.738; 0.576; 0.185; 1.212; 1.478 | — |
| SECONDARY DBTP: Change From Baseline in Degree of Pancreatic Injury/Inflammation Through Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) Following 12 Weeks of Treatment With Evinacumab Assessed by Apparent Diffusion Coefficient (ADC) |
0.00144; 0.00154; -0.00007; 0.00001 | — |
| SECONDARY SBTP: Change From Baseline to Degree of Pancreatic Injury/Inflammation Through DW-MRI Following 24 Weeks of Treatment With Evinacumab as Assessed by ADC |
-0.00001 | — |
| SECONDARY Total Evinacumab Concentration in Serum |
NA; NA; 24.3; 561; NA; 73.6 | — |
| SECONDARY Total Angiopoietin-like (ANGPTL3) Concentration in Serum |
0.0929; 0.105; 0.0950; 0.258; 0.111; 0.265 | — |
| SECONDARY Number of Participants With Antidrug Antibodies (ADA) |
14; 29; 1; 4; 0; 0 | — |
| SECONDARY DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs |
11; 25; 3; 4 | — |
| SECONDARY SBTP: Number of Participants With TEAEs and Serious TEAEs |
38; 15 | — |
| SECONDARY Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin |
0; 1; 0; 0; 2; 0 | — |
Summary
The primary objective is to determine the change in Triglyceride (TG) levels following 12 weeks of repeated Intravenous (IV) doses of evinacumab.
Eligibility Criteria
Key Inclusion Criteria
- 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
Key Exclusion Criteria
- 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT03452228). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.