Severe Hypertriglyceridemia (sHTG)
Conditions
Brief summary
The primary objective is to determine the change in Triglyceride (TG) levels following 12 weeks of repeated Intravenous (IV) doses of evinacumab.
Interventions
DRUGevinacumab
Administered by Intravenous (IV)
DRUGPlacebo
Administered by Intravenous (IV)
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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) | 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. |
| Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) | 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. |
| 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 | 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. |
| 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) | 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. |
| SBTP: Change From Baseline to Degree of Pancreatic Injury/Inflammation Through DW-MRI Following 24 Weeks of Treatment With Evinacumab as Assessed by ADC | 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. |
| 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 overall group during DBTP and SBTP was reported. |
| Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Up to 44 weeks | Concentrations of total ANGPTL3 in serum by time and DBTP treatment group reported |
| Number of Participants With Antidrug Antibodies (ADA) | 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. |
| DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | 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. |
| SBTP: Number of Participants With TEAEs and Serious TEAEs | 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. |
| Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | 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. |
| Total Evinacumab Concentration in Serum | Up to 44 weeks | Concentrations of total evinacumab in serum by time and DBTP treatment group reported |
Countries
Canada, Italy, United Kingdom, United States
Participant flow
Recruitment details
A total of 17 centers enrolled participants in Italy, Canada, the United Kingdom of Great Britain and Northern Ireland, and the United States.
Pre-assignment details
Based upon information (or lack of information) on genotype in medical history at screening, eligible patients were enrolled into 1 of 3 cohorts; 51 of 74 patients screened were randomized and treated during the double-blind treatment period (DBTP).
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Q4W (DBTP) Participants received placebo matching evinacumab IV Q4W on days 1, 29, and 57 during 12-week DBTP. | 16 |
| Evinacumab 15 mg/kg (DBTP) Participants received IV infusion of evinacumab 15 mg/kg Q4W on days 1, 29, and 57 during the 12-week DBTP. | 35 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment Period (12 Weeks) | Adverse Event | 0 | 2 | 0 |
| Double-Blind Treatment Period (12 Weeks) | Lost to Follow-up | 1 | 1 | 0 |
| Double-Blind Treatment Period (12 Weeks) | Randomized but not treated | 1 | 0 | 0 |
| Single-Blind Treatment Period (12 Weeks) | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Evinacumab 15 mg/kg (DBTP) | Total | Placebo IV Q4W (DBTP) |
|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 10.23 | 47.8 years STANDARD_DEVIATION 11.13 | 46.2 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 45 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Triglycerides | 2475.1 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 1597.2 | 2421.4 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 1555.5 | 2303.8 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 1503.81 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 41 Participants | 12 Participants |
| Sex: Female, Male Female | 17 Participants | 24 Participants | 7 Participants |
| Sex: Female, Male Male | 18 Participants | 27 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 35 | 0 / 15 | 0 / 32 |
| other Total, other adverse events | 11 / 16 | 20 / 35 | 13 / 15 | 22 / 32 |
| serious Total, serious adverse events | 3 / 16 | 4 / 35 | 4 / 15 | 11 / 32 |
Outcome results
Primary
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.
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
Population: The FAS included all randomized participants who received any double-blind study drug based on the treatment assigned (as randomized). Mixed-effect Model for Repeated Measures (MMRM) method assessed within-patient treatment comparisons (using an unstructured covariance matrix), while accounting for baseline TG, study visit, and baseline TG by study visit interaction. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 Percent Change | Standard Error 99.1 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting Triglycerides (TG) Level Following 12 Weeks of Repeated IV Doses of Evinacumab in Actual Cohort 3 Participants | -37.2 Percent Change | Standard Error 42.9 |
95% CI: [-89.4, 1238.9]
95% CI: [-82.2, 121.2]
Secondary
Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS)
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.
Time frame: Baseline, Week 12 (DBTP), Week 24 (SBTP)
Population: Patient-reported outcomes (PRO) analysis set included all randomized participants who received any double-blind study treatment with a baseline and at least 1 non-missing post-baseline PRO evaluation. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS) | DBTP: Change at Week 12 | -0.69 Score on a Scale | Standard Deviation 6.93 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS) | DBTP: Change at Week 12 | -0.74 Score on a Scale | Standard Deviation 5.102 |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Change From Baseline in Total Score of Participants Reported Abdominal and Gastrointestinal (GI) Symptoms Using Hypertriglyceridemia and Acute Pancreatitis Symptom Scale (HAP-SS) | SBTP: Change at Week 24 | -0.12 Score on a Scale | Standard Deviation 5.033 |
Secondary
Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB)
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.
Time frame: Baseline, Week 12 (DBTP), Week 24 (SBTP)
Population: PRO analysis set includes all randomized participants who received any double-blind study treatment with a baseline and at least 1 non-missing post-baseline PRO evaluation. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) | DBTP: Change at Week 12 | -2.267 Score on a Scale | Standard Deviation 5.5897 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) | DBTP: Change at Week 12 | 2.021 Score on a Scale | Standard Deviation 15.2152 |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Change From Baseline in Total Score of Participants Reported Dietary Behavior Questionnaire (HAP-DB) | SBTP: Change at Week 24 | -1.255 Score on a Scale | Standard Deviation 7.7864 |
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
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.
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
Population: PET analysis set included all randomized participants who received any double-blind study treatment with a baseline and a post-baseline (positron emission tomography) PET evaluation. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmax: Baseline | 2.318 gram/milliliter (g/ml) | Standard Deviation 0.6168 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmax: Change at Week 12 | 0.576 gram/milliliter (g/ml) | Standard Deviation 1.0628 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmean: Baseline | 1.212 gram/milliliter (g/ml) | Standard Deviation 0.2513 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmean: Change at Week 12 | 0.175 gram/milliliter (g/ml) | Standard Deviation 0.2117 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmean: Change at Week 12 | -0.007 gram/milliliter (g/ml) | Standard Deviation 0.2312 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmax: Baseline | 2.738 gram/milliliter (g/ml) | Standard Deviation 0.6027 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmean: Baseline | 1.478 gram/milliliter (g/ml) | Standard Deviation 0.2 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | SUVmax: Change at Week 12 | 0.185 gram/milliliter (g/ml) | Standard Deviation 0.583 |
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)
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.
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
Population: Magnetic resonance imaging (MRI) analysis set included all randomized participants who received any double-blind study treatment with a baseline and at least 1 post-baseline MRI evaluation. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period and number analyzed signifies to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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) | DBTP: Baseline | 0.00144 Square-millimeters per second (mm^2/sec) | Standard Deviation 0.000303 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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) | DBTP: Change at Week 12 | -0.00007 Square-millimeters per second (mm^2/sec) | Standard Deviation 0.000107 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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) | DBTP: Baseline | 0.00154 Square-millimeters per second (mm^2/sec) | Standard Deviation 0.000257 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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) | DBTP: Change at Week 12 | 0.00001 Square-millimeters per second (mm^2/sec) | Standard Deviation 0.000133 |
Secondary
DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
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.
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
Population: The double-blind safety analysis set considered for safety analyses included the randomized population who received at least 1 dose or part of a dose of double-blind study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with at least one TEAE | 11 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with at least one serious TEAE | 3 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with at least one TEAE | 25 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | DBTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with at least one serious TEAE | 4 Participants |
Secondary
Number of Participants With Antidrug Antibodies (ADA)
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.
Time frame: Up to 44 weeks
Population: The ADA analysis set included all randomized participants who received any study drug and had at least 1 non-missing ADA result following the first dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Negative any Time | 14 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Pre-existing Immunoreactivity | 1 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Treatment-boosted Response | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Treatment-emergent Response | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Treatment-emergent Response | 1 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Negative any Time | 29 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Treatment-boosted Response | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Antidrug Antibodies (ADA) | Pre-existing Immunoreactivity | 4 Participants |
Secondary
Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin
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.
Time frame: Baseline up to 44 weeks
Population: The double-blind safety analysis set considered for safety analyses included the randomized population who received at least 1 dose or part of a dose of double-blind study drug. The single-blind safety analysis set considered for safety analyses included the randomized population who received at least 1 dose or part of a dose of single-blind study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >1.5 ULN - <=2 ULN and =<1.5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >2 ULN and <=3 ULN and <=2 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >5 ULN and <=10 ULN and <=5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >20 ULN and <=20 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >3 ULN and <=5 ULN and <=3 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >3 ULN and <=5 ULN and <=3 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >5 ULN and <=10 ULN and <=5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >2 ULN and =< 2.0 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT 10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | (ALT>3ULN&TB>2ULN)&(ALT<=3ULN or TB<=2ULN) at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >2 ULN and <=3 ULN and <=2 ULN at baseline | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >20 ULN and <=20 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Alkaline Phosphatase >1.5 ULN and =< 1.5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >1.5 ULN - <=2 ULN and =<1.5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >2 ULN and <=3 ULN and <=2 ULN at baseline | 1 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >3 ULN and <=5 ULN and <=3 ULN at BL | 2 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >5 ULN and <=10 ULN and <=5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT 10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >20 ULN and <=20 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >2 ULN and <=3 ULN and <=2 ULN at BL | 2 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >3 ULN and <=5 ULN and <=3 ULN at BL | 1 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >5 ULN and <=10 ULN and <=5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >20 ULN and <=20 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >2 ULN and =< 2.0 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Alkaline Phosphatase >1.5 ULN and =< 1.5 ULN at BL | 0 Participants |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | (ALT>3ULN&TB>2ULN)&(ALT<=3ULN or TB<=2ULN) at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Alkaline Phosphatase >1.5 ULN and =< 1.5 ULN at BL | 2 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >20 ULN and <=20 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >20 ULN and <=20 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT 10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >1.5 ULN - <=2 ULN and =<1.5 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >5 ULN and <=10 ULN and <=5 ULN at BL | 2 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >2 ULN and <=3 ULN and <=2 ULN at baseline | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | Bilirubin >2 ULN and =< 2.0 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | ALT >3 ULN and <=5 ULN and <=3 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >5 ULN and <=10 ULN and <=5 ULN at BL | 1 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >3 ULN and <=5 ULN and <=3 ULN at BL | 1 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | (ALT>3ULN&TB>2ULN)&(ALT<=3ULN or TB<=2ULN) at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >10 ULN and <=20 ULN and <=10 ULN at BL | 0 Participants |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Number of Participants With Liver Function Laboratory Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Total Bilirubin | AST >2 ULN and <=3 ULN and <=2 ULN at BL | 0 Participants |
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
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.
Time frame: Weeks 2, 4, 6, 8, 12, 16, 20, and 24
Population: The FAS included all randomized participants who received any double-blind study drug based on the treatment assigned (as randomized). Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period and number analyzed signifies to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 4 | -19.0 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 16 | -16.2 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 20 | -37.2 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 2 | -28.3 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 6 | -47.1 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 8 | -29.5 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 24 | -7.7 Percent Change |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 12 | -27.7 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 8 | -69.2 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 6 | -84.6 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 16 | -71.3 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 4 | -48.0 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 2 | -77.5 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 20 | -65.5 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 24 | -75.7 Percent Change |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | 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 | Percent change at Week 12 | -64.8 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 24 | -71.4 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 2 | -74.4 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 4 | -70.3 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 6 | -71.3 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 8 | -62.5 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 12 | -81.7 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 16 | -80.4 Percent Change |
| Evinacumab IV 15mg/kg Q4W (SBTP) | 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 | Percent change at Week 20 | -75.7 Percent Change |
Secondary
Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group
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.
Time frame: DBTP: Baseline, Weeks 2, 4, 6, 8, 12; SBTP: Weeks 16, 20, and 24
Population: The FAS included all randomized participants who received any double-blind study drug based on the treatment assigned (as randomized). Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period and number analyzed signifies to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 2 | 1.99 Percent Change | Standard Deviation 45.687 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 4 | -3.52 Percent Change | Standard Deviation 41.029 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 6 | 92.56 Percent Change | Standard Deviation 262.368 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 8 | 4.83 Percent Change | Standard Deviation 38.941 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 12 | 17.47 Percent Change | Standard Deviation 47.61 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 6 | -52.69 Percent Change | Standard Deviation 40.214 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 2 | -51.38 Percent Change | Standard Deviation 33.16 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 12 | -42.03 Percent Change | Standard Deviation 61.086 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 4 | -43.70 Percent Change | Standard Deviation 39.119 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 8 | -32.86 Percent Change | Standard Deviation 64.787 |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 20 | -38.09 Percent Change | Standard Deviation 49.07 |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 16 | -39.23 Percent Change | Standard Deviation 46.026 |
| Evinacumab IV 15mg/kg Q4W (SBTP) | Percent Change From Baseline in Fasting TG Level Following 2 to 24 Weeks of Repeated IV Doses of Evinacumab Overall Group | Percent change at Week 24 | -35.86 Percent Change | Standard Deviation 65.011 |
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
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.
Time frame: Baseline (Week 0 DBTP), Week 24 (SBTP)
Population: MRI analysis set included all randomized participants who received any double-blind study treatment with a baseline and at least 1 post-baseline MRI evaluation. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure for specified arm/period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | 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 mm^2/sec | Standard Deviation 0.000166 |
Secondary
SBTP: Number of Participants With TEAEs and Serious TEAEs
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.
Time frame: From day of first SB study treatment to day of last SB treatment + 24 weeks
Population: The single-blind safety analysis set considered for safety analyses included the randomized population who received at least 1 dose or part of a dose of single-blind study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | SBTP: Number of Participants With TEAEs and Serious TEAEs | Participants with at least one TEAE | 38 Participants |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | SBTP: Number of Participants With TEAEs and Serious TEAEs | Participants with at least one Serious TEAE | 15 Participants |
Secondary
Total Angiopoietin-like (ANGPTL3) Concentration in Serum
Concentrations of total ANGPTL3 in serum by time and DBTP treatment group reported
Time frame: Up to 44 weeks
Population: The total target analysis set is defined as all randomized participants who received any study drug and have at least 1 non-missing measurement of total ANGPTL3 concentration following the first dose of study drug. Here, number analyzed signifies to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 8: Pre-Dose | 0.114 mg/L | Standard Deviation 0.0333 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 0: Pre-Dose | 0.0929 mg/L | Standard Deviation 0.0313 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 0: End of Infusion | 0.0950 mg/L | Standard Deviation 0.0256 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 4: Pre-Dose | 0.111 mg/L | Standard Deviation 0.0272 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 4: End of Infusion | 0.106 mg/L | Standard Deviation 0.0205 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 8: End of Infusion | 0.137 mg/L | Standard Deviation 0.0977 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 12: Pre-Dose | 0.107 mg/L | Standard Deviation 0.0273 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 12: End of Infusion | 0.250 mg/L | Standard Deviation 0.094 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 20: Pre-Dose | 0.302 mg/L | Standard Deviation 0.0973 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 20: End of Infusion | 0.407 mg/L | Standard Deviation 0.144 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 24: Post Last Dose 4 Weeks | 0.294 mg/L | Standard Deviation 0.0954 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 28: Post Last Dose 8 Weeks | 0.311 mg/L | Standard Deviation 0.0701 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 36: Post Last Dose 16 Weeks | 0.134 mg/L | Standard Deviation 0.0487 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 44: Post Last Dose 24 Weeks | 0.107 mg/L | Standard Deviation 0.0322 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 24: Post Last Dose 4 Weeks | 0.331 mg/L | Standard Deviation 0.113 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 8: Pre-Dose | 0.307 mg/L | Standard Deviation 0.0758 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 12: End of Infusion | 0.394 mg/L | Standard Deviation 0.102 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 0: Pre-Dose | 0.105 mg/L | Standard Deviation 0.0327 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 36: Post Last Dose 16 Weeks | 0.193 mg/L | Standard Deviation 0.0969 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 0: End of Infusion | 0.258 mg/L | Standard Deviation 0.0745 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 20: Pre-Dose | 0.346 mg/L | Standard Deviation 0.101 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 4: Pre-Dose | 0.265 mg/L | Standard Deviation 0.0932 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 28: Post Last Dose 8 Weeks | 0.265 mg/L | Standard Deviation 0.0984 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 4: End of Infusion | 0.404 mg/L | Standard Deviation 0.132 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 20: End of Infusion | 0.422 mg/L | Standard Deviation 0.118 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 8: End of Infusion | 0.415 mg/L | Standard Deviation 0.0875 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 44: Post Last Dose 24 Weeks | 0.131 mg/L | Standard Deviation 0.0489 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Angiopoietin-like (ANGPTL3) Concentration in Serum | Week 12: Pre-Dose | 0.310 mg/L | Standard Deviation 0.0911 |
Secondary
Total Evinacumab Concentration in Serum
Concentrations of total evinacumab in serum by time and DBTP treatment group reported
Time frame: Up to 44 weeks
Population: Pharmacokinetic (PK) analysis set included all randomized participants who received any study drug and have at least 1 non-missing measurement of evinacumab concentration following the first dose of the study drug. Here, number analyzed signifies to participants evaluable for this outcome at given timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 0: End Of Infusion | 24.3 milligram per liter (mg/L) | Standard Deviation 97 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 0: Pre-Dose | NA milligram per liter (mg/L) | — |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 4: Pre-Dose | NA milligram per liter (mg/L) | — |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 4: End of Infusion | 0.334 milligram per liter (mg/L) | Standard Deviation 1.25 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 8: Pre-Dose | NA milligram per liter (mg/L) | — |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 8: End of Infusion | 28.8 milligram per liter (mg/L) | Standard Deviation 104 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 12: Pre-Dose | 0.00639 milligram per liter (mg/L) | Standard Deviation 0.0239 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 12: End Of Infusion | 544 milligram per liter (mg/L) | Standard Deviation 159 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 20: Pre-Dose | 113 milligram per liter (mg/L) | Standard Deviation 51.9 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 20: End Of Infusion | 675 milligram per liter (mg/L) | Standard Deviation 146 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 24: Post Last Dose 4 Weeks | 121 milligram per liter (mg/L) | Standard Deviation 76.7 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 28: Post Last Dose 8 Weeks | 43.1 milligram per liter (mg/L) | Standard Deviation 47.8 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 36: Post Last Dose 16 Weeks | 0.239 milligram per liter (mg/L) | Standard Deviation 0.25 |
| Actual Cohort 3: DB Placebo/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 44: Post Last Dose 24 Weeks | 0.0190 milligram per liter (mg/L) | Standard Deviation 0.0464 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 24: Post Last Dose 4 Weeks | 134 milligram per liter (mg/L) | Standard Deviation 77.2 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 12: End Of Infusion | 662 milligram per liter (mg/L) | Standard Deviation 146 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 0: Pre-Dose | NA milligram per liter (mg/L) | — |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 0: End Of Infusion | 561 milligram per liter (mg/L) | Standard Deviation 203 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 36: Post Last Dose 16 Weeks | 1.98 milligram per liter (mg/L) | Standard Deviation 7.41 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 4: Pre-Dose | 73.6 milligram per liter (mg/L) | Standard Deviation 38.3 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 20: Pre-Dose | 160 milligram per liter (mg/L) | Standard Deviation 119 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 4: End of Infusion | 590 milligram per liter (mg/L) | Standard Deviation 153 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 28: Post Last Dose 8 Weeks | 40.2 milligram per liter (mg/L) | Standard Deviation 44.6 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 8: Pre-Dose | 109 milligram per liter (mg/L) | Standard Deviation 57.2 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 20: End Of Infusion | 680 milligram per liter (mg/L) | Standard Deviation 199 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 8: End of Infusion | 586 milligram per liter (mg/L) | Standard Deviation 119 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 44: Post Last Dose 24 Weeks | 0.0680 milligram per liter (mg/L) | Standard Deviation 0.102 |
| Actual Cohort 3: DB Evinacumab/SB Evinacumab IV 15mg/kg Q4W | Total Evinacumab Concentration in Serum | Week 12: Pre-Dose | 124 milligram per liter (mg/L) | Standard Deviation 81.4 |