Clinical trial NCT03452228: Safety and Efficacy Following Repeat-Dose of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute Pancreatitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Hypertriglyceridemia (sHTG)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-03-02
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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:

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

Primary outcomes:
measure: Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants
timeFrame: 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:
measure: Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group
timeFrame: DBTP: Baseline, Weeks 2, 4, 6, 8, 12; SBTP: Weeks 16, 20, and 24
measure: 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
timeFrame: Weeks 2, 4, 6, 8, 12, 16, 20, and 24
measure: Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS)
timeFrame: Baseline, Week 12 (DBTP), Week 24 (SBTP)
measure: Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB)
timeFrame: Baseline, Week 12 (DBTP), Week 24 (SBTP)
measure: 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
timeFrame: 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
measure: 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)
timeFrame: 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
measure: SBTP: Change From Baseline to Degree of Pancreatic Injury/Inflammation Through DW-MRI Following 24 Weeks of Treatment With Evinacumab as Assessed by ADC
timeFrame: Baseline (Week 0 DBTP), Week 24 (SBTP)
measure: Total Evinacumab Concentration in Serum
timeFrame: Up to 44 weeks
measure: Total Angiopoietin-like (ANGPTL3) Concentration in Serum
timeFrame: Up to 44 weeks
measure: Number of Participants With Antidrug Antibodies (ADA)
timeFrame: Up to 44 weeks
measure: DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose of DB treatment to day of last dose of DB treatment + 24 weeks (if not proceeding to SBTP) or up to day before first dose of SB treatment in SBTP
measure: SBTP: Number of Participants With TEAEs and Serious TEAEs
timeFrame: From day of first SB study treatment to day of last SB treatment + 24 weeks
measure: Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin
timeFrame: Baseline up to 44 weeks
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Regeneron Research Facility
state: Florida
city: Atlanta
country: United States
facility: Regeneron Research Facility
state: Georgia
city: Kansas City
country: United States
facility: Regeneron Research Facility
state: Kansas
city: New York
country: United States
facility: Regeneron Research Facility
state: New York
city: Philadelphia
country: United States
facility: Regeneron Research Facility
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Regeneron Research Facility
state: Pennsylvania
city: Dallas
country: United States
facility: Regeneron Research Facility
state: Texas
city: Houston
country: United States
facility: Regeneron Research Facility
state: Texas
city: Milwaukee
country: United States
facility: Regeneron Research Facility
state: Wisconsin
city: Chicoutimi
country: Canada
facility: Regeneron Research Facility
state: Quebec
city: Québec
country: Canada
facility: Regeneron Research Facility
state: Quebec
city: Napoli
country: Italy
facility: Regeneron Research Facility
state: Campania
city: Rome
country: Italy
facility: Regeneron Research Facility
city: Birmingham
country: United Kingdom
facility: Regeneron Research Facility
city: London
country: United Kingdom
facility: Regeneron Research Facility
city: London
country: United Kingdom
facility: Regeneron Research Facility
city: Manchester
country: United Kingdom
facility: Regeneron Research Facility
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: