Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03452228
Recruitment Status : Completed
First Posted : March 2, 2018
Results First Posted : February 16, 2023
Last Update Posted : February 16, 2023
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : June 7, 2018
Actual Primary Completion Date : December 17, 2019
Actual Study Completion Date : July 23, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatitis
Drug Information available for: Evinacumab

Arm Intervention/treatment
Experimental: evinacumab Drug: evinacumab
Administered by Intravenous (IV)
Other Name: REGN1500

Experimental: Placebo Drug: Placebo
Administered by Intravenous (IV)




Primary Outcome Measures :
  1. Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group [ Time Frame: 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 overall group during DBTP and SBTP was reported.

  2. 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 [ Time Frame: Weeks 2, 4, 6, 8, 12, 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 participants were reported.

  3. Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS) [ Time Frame: Baseline, Week 12 (DBTP), Week 24 (SBTP) ]
    HAP-SS: 19-item measure of symptoms with a 24-hour recall period. 4 pain items were captured on 0-10-point severity NRS, each scored 0 (No pain) to 10 (Worst possible pain), while 15 non-pain items captured on 5-point frequency Likert scale, each scored from 1 (None of the time) to 5 (All of the time). Pain domain 4 items: stomach pain average, worst stomach pain, worst back pain, stomach pain after eating (score range: 0 to 40). Abdominal symptoms domain 6 items: bloated, nausea, vomiting, passed excessive gas, diarrhea, light-colored or greasy stool (score range: 6 to 30). Physical symptoms domain 5 items: fever, insomnia, excessive sweating, dizziness, racing heart rate (score range 5 to 25). Other symptoms domain 4 items: fatigue, loss of appetite, hungry after eating, felt full after eating a small amount (score range 4 to 20). All items were transformed on to total score ranges from 0 (no symptoms) to 100 (severe symptoms). Negative change indicates better condition.

  4. Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) [ Time Frame: Baseline, Week 12 (DBTP), Week 24 (SBTP) ]
    Dietary habits and impact were measured by the Hypertriglyceridemia and Acute Pancreatitis Dietary Behavior (HAP-DB) questionnaire, a 6- item measure of dietary behavior that had a 24-hour recall period using a 5-point frequency Likert scale (1= None of the time to 5= All of the time) and a dietary impact total score, ranging from 6 (no impact) to 30 (severe impact). The six HAP-DB items were: 1 -amount of food eaten), 2 -fatty or greasy food), 3 -carbohydrates), i4 (-sugar or sugary foods), 5 -alcohol intake), 6 -skipped meal). The total score was calculated as the sum of the six item scores and then transformed to a 0-100 score, where lower score indicates less of an issue with dietary behaviors. Transformed score = 100 * (score - minimum possible score) / (maximum - minimum possible score). Change from baseline in total score of participants reported daily dietary habits and impact questionnaire during DBTP and SBTP was reported.

  5. 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 [ Time Frame: 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 ]
    18F-FDG-PET is a molecular imaging modality that has demonstrated high sensitivity in the in vivo detection of glycolytic tissues, including tumors and inflammatory foci. 18F-FDG PET has been applied in a clinical setting to the assessment of inflammation for a variety of indications, including auto immune pancreatitis, atherosclerosis and infection. 18F-FDG-PET was performed at baseline (placebo run-in period) and following 12 weeks of study treatment (double-blind treatment period) as a method to measure inflammation in the pancreas. Here, SUVmax was standardized uptake values maximum and SUVmean was mean standardized uptake values were reported.

  6. 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) [ Time Frame: 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 ]
    In DW-MRI the random diffusion of water molecules occurring within intracellular, extracellular and intravascular spaces were measured, enabling detection of macroscopic soft tissue pathology such as edema, necrosis and fibrosis. The ADC was a principal metric quantified in DW-MRI experiments, where ADC values was mapped across a region of interest at a spatial resolution of ~3*3*5 cubic millimeter (mm^3). Normal pancreas ADCs were considered as (1.77±0.32)*103 square-millimeters per second (mm^2/sec) while acute pancreatitis ADCs were (1.32±0.32)* 103 mm^2/sec showing a significant window for measuring projected inflammatory changes in pancreas. DW-MRI was performed at baseline (placebo run-in period) and following 12 weeks of study treatment (double-blind treatment period) as a method to measure inflammation in the pancreas. Change from baseline in degree of pancreatic injury/inflammation through DW-MRI following 12 weeks of treatment with evinacumab assessed by ADC was reported.

  7. SBTP: 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: Baseline (Week 0 DBTP), Week 24 (SBTP) ]
    In DW-MRI, the random diffusion of water molecules occurring within intracellular, extracellular and intravascular spaces were measured, enabling detection of macroscopic soft tissue pathology such as edema, necrosis and fibrosis. The ADC was a principal metric quantified in DW-MRI experiments, where ADC values was mapped across a region of interest at a spatial resolution of ~3*3*5 mm^3. Normal pancreas ADCs were considered as (1.77±0.32)*103 mm^2/sec while acute pancreatitis ADCs are (1.32±0.32)* 103 mm^2/sec showing a significant window for measuring the projected inflammatory changes in the pancreas. Change from baseline to degree of pancreatic injury/inflammation through DW-MRI following 24 weeks of treatment with evinacumab assessed by ADC was reported.

  8. Total Evinacumab Concentration in Serum [ Time Frame: Up to 44 weeks ]
    Concentrations of total evinacumab in serum by time and DBTP treatment group reported

  9. Total Angiopoietin-like (ANGPTL3) Concentration in Serum [ Time Frame: Up to 44 weeks ]
    Concentrations of total ANGPTL3 in serum by time and DBTP treatment group reported

  10. Number of Participants With Antidrug Antibodies (ADA) [ Time Frame: Up to 44 weeks ]
    ADA were classified as the following: 1) Negative any time (negative in ADA assay at all time points); 2) Pre-existing immunoreactivity (ADA positive response at baseline with all post treatment ADA results negative or ADA positive response at baseline with all post treatment responses less than 9-fold of baseline titer levels); 3) Treatment-boosted Response (ADA positive response in assay post first dose that is at least 9-fold over baseline titer levels, when baseline results were positive); 4) Treatment-emergent ADA response (ADA positive response post first dose, when baseline results were negative or missing). Number of participants with ADA by DBTP treatment group reported.

  11. DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: 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 ]
    TEAEs are AEs that developed or worsened or became serious during the respective TEAE period. Number of participants who experienced a TEAE/serious TEAE during the DBTP reported.

  12. SBTP: Number of Participants With TEAEs and Serious TEAEs [ Time Frame: From day of first SB study treatment to day of last SB treatment + 24 weeks ]
    TEAEs are AEs that developed or worsened or became serious during the respective TEAE period. Number of participants who experienced a TEAE/serious TEAE during the SBTP reported.

  13. Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin [ Time Frame: Baseline up to 44 weeks ]
    The number of participants with laboratory abnormalities in ALT, AST, ALP, and total bilirubin that fell into the pre-defined potentially clinically significant value (PCSV) categories reported: ALT: greater than (>)2 upper limit of normal (ULN) and baseline (BL) less than or equal to (<=) 2 ULN, less than (>) 3 ULN and baseline <= 3 ULN, >5 ULN and baseline <= 5 ULN, >10 ULN and baseline ≤ 10 ULN, >20 ULN and baseline <= 20 ULN; AST: >2 ULN and baseline ≤ 2 ULN, >3 ULN and baseline <= 3 ULN, >5 ULN and baseline <= 5 ULN, >10 ULN and baseline <= 10 ULN, >20 ULN and baseline <= 20 ULN; ALP: > 1.5 ULN and baseline <= 1.5 ULN; Total Bilirubin (TB): > 1.5 ULN and baseline <= 1.5 ULN, > 2 ULN and baseline <= 2 ULN.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03452228


Locations
Layout table for location information
United States, Florida
Regeneron Research Facility
Boca Raton, Florida, United States, 33434
United States, Georgia
Regeneron Research Facility
Atlanta, Georgia, United States, 30328
United States, Kansas
Regeneron Research Facility
Kansas City, Kansas, United States, 66160
United States, New York
Regeneron Research Facility
New York, New York, United States, 10029
United States, Pennsylvania
Regeneron Research Facility
Philadelphia, Pennsylvania, United States, 19104
Regeneron Research Facility
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Regeneron Research Facility
Dallas, Texas, United States, 75390
Regeneron Research Facility
Houston, Texas, United States, 77030
United States, Wisconsin
Regeneron Research Facility
Milwaukee, Wisconsin, United States, 53226
Canada, Quebec
Regeneron Research Facility
Chicoutimi, Quebec, Canada, G7H7K9
Regeneron Research Facility
Québec, Quebec, Canada, G1V4W2
Italy
Regeneron Research Facility
Napoli, Campania, Italy, 80131
Regeneron Research Facility
Rome, Italy, 00161
United Kingdom
Regeneron Research Facility
Birmingham, United Kingdom, B15 2TH
Regeneron Research Facility
London, United Kingdom, NW3 2QG
Regeneron Research Facility
London, United Kingdom, SE1 7EH
Regeneron Research Facility
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] October 15, 2019
Statistical Analysis Plan  [PDF] May 20, 2019

Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03452228    
Other Study ID Numbers: R1500-HTG-1522
2016-003307-62 ( EudraCT Number )
First Posted: March 2, 2018    Key Record Dates
Results First Posted: February 16, 2023
Last Update Posted: February 16, 2023
Last Verified: January 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatitis
Hypertriglyceridemia
Pancreatic Diseases
Digestive System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases