Familial Partial Lipodystrophy
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in a randomized treatment (RT) period in participants with familial partial lipodystrophy (FPL). Following the randomized treatment period, participants who did not enter the open-label extension (OLE) period went straight to the 13-week post-treatment (PT) follow-up period and participants who were entered in the OLE period continued to receive volanesorsen for another 52 weeks (Weeks 53 to 104). Following the Week 104 visit of the OLE period, participants had an option of continued dosing for up to an additional 52 weeks (Week 105 to 156). Participants who did not enter the OLE period went straight to a 13-week post-treatment follow-up period. Following the Week 104 OLE period, participants were entered a 13-week post-treatment follow-up period, if they did not choose the option for continued dosing.
Interventions
DRUGvolanesorsen
300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW).
DRUGPlacebo
Volanesorsen-matching placebo administered SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Akcea Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must give written informed consent to participate in the study (signed and dated) and any authorizations required by law. * Clinical diagnosis of familial partial lipodystrophy (FPL) plus diagnosis of type 2 diabetes mellitus, hypertriglyceridemia, and fatty liver. * Diagnosis of FPL is based on deficiency of subcutaneous body fat in a partial fashion assessed by physical examination and low skinfold thickness in anterior thigh by caliper measurement: men (less than or equal to \[≤\] 10 millimeters \[mm\]) and women (≤ 22 mm), and at least 1 of the following: 1. Genetic diagnosis of FPL OR 2. Family history of FPL or of similar abnormal fat distribution plus 1 Minor Criteria OR 3. In the absence of FPL-associated genetic variant or family history, 2 Minor Criteria and body mass index (BMI) less than (\<) 35 kilogram per meter square (kg/m\^2). * Diabetes not well controlled on antidiabetic therapy with glycated hemoglobin (Hb) HbA1c more than or equal to (≥) 7 percentage (%) to ≤ 12% at Screening. * Hypertriglyceridemia with fasting triglycerides (TG) levels greater than or equal to (≥) 500 milligrams per deciliter (mg/dL) (≥ 5.7 millimoles per liter \[mmol/L\]) at Screening and Qualification visit, or Fasting TG levels ≥ 200 (≥ 2.26 mmol/L) at both Screening and Qualification Visits for participants who meet the genetic or family history criteria. * Presence of hepatosteatosis (fatty liver), as evidenced by a screening magnetic resonance imaging (MRI) indicating a hepatic fat fraction (HFF) ≥ 6.4%.
Exclusion criteria
* A diagnosis of generalized lipodystrophy. * A diagnosis of acquired partial lipodystrophy. * Acute pancreatitis within 4 weeks of Screening. * History within 6 months of Screening of acute or unstable cardiac condition. * Low-density lipoprotein cholesterol (LDL-C) more than (\>) 130 mg/dL on maximal tolerated statin therapy. * Platelet count \< lower limit of normal (LLN). * Treatment with metreleptin within the last 3 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) | Baseline to Month 3 | Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 predose fasting assessment. Month 3 value was defined as the average of Week 12 and Week 13 fasting TG assessments of the randomized treatment period. The data was analyzed using an analysis of covariance (ANCOVA) model with the randomization stratification factor (diagnosis of disease with or without genetics and family history) and treatment group as factors and log-transformed baseline fasting TG as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI | Baseline, Months 6 and 12 | Baseline was defined as the last non-missing assessment prior to the first dose of study drug in the randomized treatment period. Open-label extension period: Month 6 value was defined as Week 77 or Week 78 for MRI assessment and Month 12 value was defined as Week 102 or Week 104 for MRI assessment. Hepatic steatosis is a reversible condition in which large vacuoles of triglyceride fat accumulate in the liver cells, causing nonspecific inflammation. Hepatic Steatosis was assessed by hepatic fat fraction using MRI. |
| Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, Months 3, 6, 9, and 12 | Baseline was defined as the last non-missing assessment prior to the first dose of study drug. Randomized treatment period: The Month 3 value was defined as Week 13, Month 6 value was defined as Week 26, Month 9 value was defined as Week 38 and Month 12 value was defined as Week 52. |
| Open Label Extension Period: Change From Baseline in HbA1c | Baseline, Months 3, 6, 9, and 12 | Baseline was defined as the last non-missing assessment prior to the first dose of study drug. Open-label extension period: Month 3 value was defined as Week 65, Month 6 value was defined as Week 78, Month 9 value was defined as Week 90 and Month 12 value was defined as Week 104. |
| Randomized Treatment Period: Percentage of Participants Who Achieved Greater Than or Equal to (≥) 40% Reduction in Fasting Triglyceride and ≥ 30% Reduction of Hepatic Fat Fraction at Month 6 | Month 6 | The baseline of TG is defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. The baseline of hepatic fat fraction is defined as the last non-missing assessment prior to the first dose of study drug. Randomized treatment period: Month 6 value was defined as average of Week 25 and Week 26 for fasting TG and Week 25 or Week 26 for hepatic fat fraction. |
| Randomized Treatment Period: Change From Baseline in Disease Burden Score | From the first dose of study drug to Week 52 | The Disease Burden Score is a questionnaire that allows participants to self-report their chronic conditions and then assess the degree to which each condition interferes with daily activities. |
| Open-Label Extension Period: Change From Baseline in Disease Burden Score | From the first dose of study drug in open label extension period to Week 117 | The Disease Burden Score is a questionnaire that allows participants to self-report their chronic conditions and then assess the degree to which each condition interferes with daily activities. |
| Randomized Treatment Period: Patient-Reported Pain | From the first dose of study drug up to Week 52 | Patient-reported pain was assessed by rating pain symptoms at its worst and least for the last 24 hours, on average, and at the moment, with 0 as the lowest score (no pain) and 10 as the highest score (worst pain as you can imagine). Patient-reported pain was also assessed by rating pain symptoms (rate pain on average, rate pain right now) that interfered with general activity, interfered with mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life, with 0 as the lowest score (did not interfered) and 10 as the highest score (completely interfered). The scores from each assessment time point were averaged for all of the below reported categories. |
| Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI) | Baseline, Months 6 and 12 | Baseline was defined as the last non-missing assessment prior to the first dose of study drug in the randomized treatment period. Randomized treatment period: Month 6 value was defined as Week 25 or Week 26 for MRI assessment and Month 12 was defined as Week 50 or Week 52 for MRI assessment. Hepatic steatosis is a reversible condition in which large vacuoles of triglyceride fat accumulate in the liver cells, causing nonspecific inflammation. Hepatic Steatosis was assessed by hepatic fat fraction using MRI. |
| Randomized Treatment Period: Patient-Reported Hunger | From the first dose of study drug up to Week 52 | Patient-reported hunger was assessed by participants who completed a questionnaire about: how hungry you feel, how satisfied you feel, how full you feel, how much you think you can eat, like to eat something sweet, like to eat something salty, like to eat something savory and like to eat something fatty. Participants also rated the palatability of meals that included visual appeal, smell, taste, and aftertaste. Scores of 1-39 were categorized as mild, 40-69 as moderate, and 70-100 as severe. The scores from each assessment time point were averaged for all of the below reported categories. |
| Open Label Extension Period: Patient-Reported Hunger | From the first dose of study drug in open label extension period up to Week 117 | Patient-reported hunger was assessed by participants who completed a questionnaire about: how hungry you feel, how satisfied you feel, how full you feel, how much you think you can eat, like to eat something sweet, like to eat something salty, like to eat something savory and like to eat something fatty. Participants also rated the palatability of meals that included visual appeal, smell, taste, and aftertaste. Scores of 1-39 were categorized as mild, 40-69 as moderate, and 70-100 as severe. The scores from each assessment time point were averaged for all of the below reported categories. |
| Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Baseline, Weeks 13, 26 and 52 | The SF-36 Health Survey is a 36-item, patient-reported survey of patient health. SF-36 consists of 8 health dimensions,which are weighted sums of the questions in each section. SF-36 included 36 questions related to 8 health dimensions:physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning,emotional role functioning, and mental health. Each dimension was scored on a scale of 0 to 100 where, higher score = better quality of life. A positive change from Baseline indicates improvement. |
| Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Baseline, Weeks 65, 78 and 104 | The SF-36 Health Survey is a 36-item, patient-reported survey of patient health. SF-36 consists of 8 health dimensions,which are weighted sums of the questions in each section. SF-36 included 36 questions related to 8 health dimensions:physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning,emotional role functioning, and mental health. Each dimension was scored on a scale of 0 to 100 where, higher score = better quality of life. A positive change from Baseline indicates improvement. |
| Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Baseline, Weeks 13, 26 and 52 | EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A negative change from baseline indicates worsening. A positive change from baseline indicates improvement. |
| Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Baseline, Weeks 65, 78 and 104 | EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A negative change from baseline indicates worsening. A positive change from baseline indicates improvement. |
| Open Label Extension Period: Patient-Reported Pain | From the first dose of study drug in open label extension period up to Week 117 | Patient-reported pain was assessed by rating pain symptoms at its worst and least for the last 24 hours, on average, and at the moment, with 0 as the lowest score (no pain) and 10 as the highest score (worst pain as you can imagine). Patient-reported pain was also assessed by rating pain symptoms (rate pain on average, rate pain right now) that interfered with general activity, interfered with mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life, with 0 as the lowest score (did not interfered) and 10 as the highest score (completely interfered). The scores from each assessment time point were averaged for all of the below reported categories. |
Countries
Belgium, Brazil, Canada, Germany, Netherlands, Russia, United States
Participant flow
Recruitment details
The study was conducted at 12 study centers in the United States, Russia, Brazil, Germany, Belgium, Canada, and Netherlands from 28 December 2015 to 13 November 2019.
Pre-assignment details
A total of 40 participants were randomized into this study.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Treatment Period: Placebo Participants received volanesorsen-matching placebo as a SC injection once-weekly from Weeks 1 to 52 of the randomized treatment period. Participants were allowed dose adjustment based on monitoring rules | 19 |
| Randomized Treatment Period: Volanesorsen Participants received 300 mg of volanesorsen as a SC injection once-weekly from Weeks 1 to 52 of the randomized treatment period. Participants were allowed dose adjustment based on monitoring rules | 21 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| OLE Period-Year 1: Week 53 to 104 | AE or SAE | 0 | 0 | 0 | 0 | 2 | 1 |
| OLE Period-Year 1: Week 53 to 104 | Investigator Judgement | 0 | 0 | 0 | 0 | 1 | 0 |
| OLE Period-Year 1: Week 53 to 104 | Other | 0 | 0 | 0 | 0 | 5 | 7 |
| OLE Period-Year 1: Week 53 to 104 | Voluntary Withdrawal | 0 | 0 | 0 | 0 | 3 | 1 |
| OLE Period-Year 2: Week 105 to 156 | Other | 0 | 0 | 0 | 0 | 1 | 2 |
| PT Follow-up: Weeks 104 to 169 | Other | 0 | 0 | 0 | 0 | 0 | 1 |
| PT Follow-up: Weeks 104 to 169 | Voluntary withdrawal | 0 | 0 | 0 | 0 | 1 | 0 |
| RT Period: Weeks 1 to 52 | Adverse Event (AE) or Serious Adverse Event (SAE) | 0 | 4 | 0 | 0 | 0 | 0 |
| RT Period: Weeks 1 to 52 | Investigator Judgement | 1 | 0 | 0 | 0 | 0 | 0 |
| RT Period: Weeks 1 to 52 | Other | 4 | 3 | 0 | 0 | 0 | 0 |
| RT Period: Weeks 1 to 52 | Voluntary withdrawal | 1 | 0 | 0 | 0 | 0 | 0 |
| RT Post Treatment Follow-up: Weeks 54-65 | AE or SAE | 0 | 0 | 1 | 0 | 0 | 0 |
| RT Post Treatment Follow-up: Weeks 54-65 | Other | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 10 | 48 years STANDARD_DEVIATION 12 | 47 years STANDARD_DEVIATION 11 |
| EQ-5D Questionnaires: Index Scores | 0.84 score on a scale STANDARD_DEVIATION 0.18 | 0.83 score on a scale STANDARD_DEVIATION 0.2 | 0.83 score on a scale STANDARD_DEVIATION 0.19 |
| EQ-5D Questionnaires: Visual Analog Scale | 71 score on a scale STANDARD_DEVIATION 18 | 70 score on a scale STANDARD_DEVIATION 18 | 71 score on a scale STANDARD_DEVIATION 17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 18 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Triglycerides | 1241.31 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1090.83 | 1290.95 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1296.19 | 1264.89 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1177.4 |
| Hemoglobin A1c | 7.84 percentage of HbA1c STANDARD_DEVIATION 1.62 | 8.25 percentage of HbA1c STANDARD_DEVIATION 1.13 | 8.04 percentage of HbA1c STANDARD_DEVIATION 1.4 |
| Hepatic Fat Fraction | 18.10 percentage (Hepatic Fat Fraction) STANDARD_DEVIATION 8.41 | 17.00 percentage (Hepatic Fat Fraction) STANDARD_DEVIATION 7.52 | 17.57 percentage (Hepatic Fat Fraction) STANDARD_DEVIATION 7.88 |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 20 Participants | 17 Participants | 37 Participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 29 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
| Short Form-36 (SF-36) Weighted Sum of Scores | 46.31 score on a scale STANDARD_DEVIATION 12.83 | 48.51 score on a scale STANDARD_DEVIATION 12.83 | 47.38 score on a scale STANDARD_DEVIATION 12.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 21 | 0 / 7 | 0 / 9 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 18 / 19 | 21 / 21 | 4 / 7 | 5 / 9 | 11 / 12 | 8 / 12 |
| serious Total, serious adverse events | 3 / 19 | 6 / 21 | 1 / 7 | 1 / 9 | 4 / 12 | 4 / 12 |
Outcome results
Primary
Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 predose fasting assessment. Month 3 value was defined as the average of Week 12 and Week 13 fasting TG assessments of the randomized treatment period. The data was analyzed using an analysis of covariance (ANCOVA) model with the randomization stratification factor (diagnosis of disease with or without genetics and family history) and treatment group as factors and log-transformed baseline fasting TG as a covariate.
Time frame: Baseline to Month 3
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. This outcome measure is reported here for the randomized treatment period only, as per the planned analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) | -21.64 percent change |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) | -88.47 percent change |
p-value: 0.000995% CI: [-104.17, -29.48]ANCOVA
Secondary
Open-Label Extension Period: Change From Baseline in Disease Burden Score
The Disease Burden Score is a questionnaire that allows participants to self-report their chronic conditions and then assess the degree to which each condition interferes with daily activities.
Time frame: From the first dose of study drug in open label extension period to Week 117
Population: Data for this outcome measure was not collected due to the change in planned analysis.
Secondary
Open Label Extension Period: Change From Baseline in HbA1c
Baseline was defined as the last non-missing assessment prior to the first dose of study drug. Open-label extension period: Month 3 value was defined as Week 65, Month 6 value was defined as Week 78, Month 9 value was defined as Week 90 and Month 12 value was defined as Week 104.
Time frame: Baseline, Months 3, 6, 9, and 12
Population: FAS included all participants who were randomized and received at least one dose of study drug in the open-label extension period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 3 | 0.42 percentage of HbA1c | Standard Deviation 1.54 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 9 | 0.35 percentage of HbA1c | Standard Deviation 1.06 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 12 | 0.00 percentage of HbA1c | Standard Deviation 0.71 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 6 | 0.35 percentage of HbA1c | Standard Deviation 1.54 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 12 | 0.30 percentage of HbA1c | Standard Deviation 0.99 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 3 | 0.91 percentage of HbA1c | Standard Deviation 2.18 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 6 | -0.75 percentage of HbA1c | Standard Deviation 0.35 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Change From Baseline in HbA1c | Change at Month 9 | -0.05 percentage of HbA1c | Standard Deviation 0.64 |
Secondary
Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores
EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A negative change from baseline indicates worsening. A positive change from baseline indicates improvement.
Time frame: Baseline, Weeks 65, 78 and 104
Population: FAS included all participants who were randomized and received at least one dose of study drug in the open-label extension period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | EQ VAS Score: Change at Week 78 | -15 score on a scale | Standard Deviation 22 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Index Score: Change at Week 78 | -0.02 score on a scale | Standard Deviation 0.03 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | EQ VAS Score: Change at Week 104 | 2 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Index Score: Change at Week 104 | 0.00 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | EQ VAS Score: Change at Week 78 | -6 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Index Score: Change at Week 65 | -0.06 score on a scale | Standard Deviation 0.08 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | EQ VAS Score: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Index Score: Change at Week 78 | -0.07 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | Index Score: Change at Week 104 | -0.27 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores | EQ VAS Score: Change at Week 65 | -4 score on a scale | Standard Deviation 16 |
Secondary
Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores
The SF-36 Health Survey is a 36-item, patient-reported survey of patient health. SF-36 consists of 8 health dimensions,which are weighted sums of the questions in each section. SF-36 included 36 questions related to 8 health dimensions:physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning,emotional role functioning, and mental health. Each dimension was scored on a scale of 0 to 100 where, higher score = better quality of life. A positive change from Baseline indicates improvement.
Time frame: Baseline, Weeks 65, 78 and 104
Population: FAS included all participants who were randomized and received at least one dose of study drug in the open-label extension period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 78 | -7.26 score on a scale | Standard Deviation 19.39 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 78 | -10.11 score on a scale | Standard Deviation 14.29 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 65 | -4.79 score on a scale | Standard Deviation 6.77 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 104 | 6.45 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 65 | -1.74 score on a scale | Standard Deviation 2.46 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 65 | 4.46 score on a scale | Standard Deviation 6.3 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 78 | 1.74 score on a scale | Standard Deviation 2.46 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 104 | 3.48 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 65 | 2.38 score on a scale | Standard Deviation 3.36 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 65 | 5.02 score on a scale | Standard Deviation 7.09 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 104 | 2.97 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 78 | -2.15 score on a scale | Standard Deviation 7.09 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 78 | -2.86 score on a scale | Standard Deviation 7.4 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 65 | -2.42 score on a scale | Standard Deviation 3.42 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 65 | -5.23 score on a scale | Standard Deviation 11.1 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 78 | 6.54 score on a scale | Standard Deviation 9.25 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 78 | -3.83 score on a scale | Standard Deviation 5.41 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 65 | 0 score on a scale | — |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 78 | -2.98 score on a scale | Standard Deviation 12.61 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 104 | 2.62 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 65 | -3.48 score on a scale | Standard Deviation 11.37 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 65 | -0.42 score on a scale | Standard Deviation 13.88 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 78 | -2.97 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Vitality: Change at Week 104 | -5.94 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 65 | -1.37 score on a scale | Standard Deviation 5.81 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 78 | 0.00 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Functioning: Change at Week 104 | -1.91 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 65 | 0.40 score on a scale | Standard Deviation 7.13 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 78 | -11.29 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Bodily Pain: Change at Week 104 | -10.49 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 65 | -2.38 score on a scale | Standard Deviation 4.42 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 78 | -4.75 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | General Health Perceptions: Change at Week 104 | -4.75 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 65 | -0 score on a scale | Standard Deviation 6.22 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 78 | -2.25 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Physical Role Functioning: Change at Week 104 | -4.50 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 78 | -10.45 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Emotional Role Functioning: Change at Week 104 | -10.45 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 65 | -2.15 score on a scale | Standard Deviation 7.58 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 78 | 0 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Social Role Functioning: Change at Week 104 | 0 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 65 | -1.12 score on a scale | Standard Deviation 13.67 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 78 | -15.70 score on a scale | — |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores | Mental Health: Change at Week 104 | 0 score on a scale | — |
Secondary
Open Label Extension Period: Patient-Reported Hunger
Patient-reported hunger was assessed by participants who completed a questionnaire about: how hungry you feel, how satisfied you feel, how full you feel, how much you think you can eat, like to eat something sweet, like to eat something salty, like to eat something savory and like to eat something fatty. Participants also rated the palatability of meals that included visual appeal, smell, taste, and aftertaste. Scores of 1-39 were categorized as mild, 40-69 as moderate, and 70-100 as severe. The scores from each assessment time point were averaged for all of the below reported categories.
Time frame: From the first dose of study drug in open label extension period up to Week 117
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | How Hungry You Feel | 29.9 score on a scale | Standard Deviation 23.3 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | How Satisfied You Feel | 54.2 score on a scale | Standard Deviation 23.3 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | How Full You Feel | 59.7 score on a scale | Standard Deviation 22.2 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | How Much You Think You Can Eat | 34.0 score on a scale | Standard Deviation 21.8 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Sweet | 73.7 score on a scale | Standard Deviation 25.4 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Salty | 65.7 score on a scale | Standard Deviation 28.1 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Savory | 65.4 score on a scale | Standard Deviation 24.7 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Fatty | 80.7 score on a scale | Standard Deviation 18.1 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Visual Appeal | 14.9 score on a scale | Standard Deviation 16.1 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Smell | 13.1 score on a scale | Standard Deviation 14.3 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Taste | 13.6 score on a scale | Standard Deviation 15.1 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Aftertaste | 48.1 score on a scale | Standard Deviation 38.6 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Hunger | Palatability | 24.4 score on a scale | Standard Deviation 23.4 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Savory | 62.7 score on a scale | Standard Deviation 30.5 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | How Hungry You Feel | 33.2 score on a scale | Standard Deviation 23.2 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Palatability | 37.3 score on a scale | Standard Deviation 20.6 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | How Satisfied You Feel | 56.3 score on a scale | Standard Deviation 20.2 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Fatty | 68.0 score on a scale | Standard Deviation 30.4 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | How Full You Feel | 52.9 score on a scale | Standard Deviation 24.4 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Taste | 32.9 score on a scale | Standard Deviation 25 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | How Much You Think You Can Eat | 34.9 score on a scale | Standard Deviation 21.5 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Visual Appeal | 35.3 score on a scale | Standard Deviation 25.9 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Sweet | 57.9 score on a scale | Standard Deviation 24 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Aftertaste | 56.9 score on a scale | Standard Deviation 29.3 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Like to Eat Something Salty | 61.9 score on a scale | Standard Deviation 22.1 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Hunger | Smell | 29.6 score on a scale | Standard Deviation 21.6 |
Secondary
Open Label Extension Period: Patient-Reported Pain
Patient-reported pain was assessed by rating pain symptoms at its worst and least for the last 24 hours, on average, and at the moment, with 0 as the lowest score (no pain) and 10 as the highest score (worst pain as you can imagine). Patient-reported pain was also assessed by rating pain symptoms (rate pain on average, rate pain right now) that interfered with general activity, interfered with mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life, with 0 as the lowest score (did not interfered) and 10 as the highest score (completely interfered). The scores from each assessment time point were averaged for all of the below reported categories.
Time frame: From the first dose of study drug in open label extension period up to Week 117
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Rate Pain on Average | 1.35 score on a scale | Standard Deviation 1.22 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Rate Pain at its Least Last 24 Hours | 0.95 score on a scale | Standard Deviation 1.04 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Rate Pain Right Now | 1.28 score on a scale | Standard Deviation 1.18 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | General Activity | 1.03 score on a scale | Standard Deviation 1.45 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Interfere With Mood | 1.27 score on a scale | Standard Deviation 1.46 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Walking Ability | 1.05 score on a scale | Standard Deviation 1.5 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Normal Work | 1.08 score on a scale | Standard Deviation 1.4 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Relations With Other People | 1.08 score on a scale | Standard Deviation 1.48 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Sleep | 1.51 score on a scale | Standard Deviation 1.83 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Enjoyment of Life | 1.23 score on a scale | Standard Deviation 1.65 |
| Randomized Treatment Period: Placebo | Open Label Extension Period: Patient-Reported Pain | Rate Pain at its Worst Last 24 Hours | 1.70 score on a scale | Standard Deviation 1.18 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Relations With Other People | 3.18 score on a scale | Standard Deviation 3.09 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Rate Pain at its Worst Last 24 Hours | 3.82 score on a scale | Standard Deviation 2.97 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Walking Ability | 3.51 score on a scale | Standard Deviation 2.83 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Rate Pain at its Least Last 24 Hours | 2.78 score on a scale | Standard Deviation 2.6 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Rate Pain on Average | 3.16 score on a scale | Standard Deviation 2.72 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Enjoyment of Life | 3.33 score on a scale | Standard Deviation 2.94 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Rate Pain Right Now | 3.49 score on a scale | Standard Deviation 2.99 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Normal Work | 3.48 score on a scale | Standard Deviation 2.98 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | General Activity | 3.28 score on a scale | Standard Deviation 2.9 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Sleep | 3.13 score on a scale | Standard Deviation 3.35 |
| Randomized Treatment Period: Volanesorsen | Open Label Extension Period: Patient-Reported Pain | Interfere With Mood | 3.23 score on a scale | Standard Deviation 2.94 |
Secondary
Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI
Baseline was defined as the last non-missing assessment prior to the first dose of study drug in the randomized treatment period. Open-label extension period: Month 6 value was defined as Week 77 or Week 78 for MRI assessment and Month 12 value was defined as Week 102 or Week 104 for MRI assessment. Hepatic steatosis is a reversible condition in which large vacuoles of triglyceride fat accumulate in the liver cells, causing nonspecific inflammation. Hepatic Steatosis was assessed by hepatic fat fraction using MRI.
Time frame: Baseline, Months 6 and 12
Population: FAS included all participants who were randomized and received at least one dose of study drug in the open-label extension period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI | Percent Change at Month 6 | -18.4 percent change | Standard Deviation 54.7 |
| Randomized Treatment Period: Placebo | Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI | Percent Change at Month 12 | -93.5 percent change | Standard Deviation 44.4 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI | Percent Change at Month 6 | -60.2 percent change | Standard Deviation 43.6 |
| Randomized Treatment Period: Volanesorsen | Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI | Percent Change at Month 12 | -22.1 percent change | Standard Deviation 47.5 |
Secondary
Randomized Treatment Period: Change From Baseline in Disease Burden Score
The Disease Burden Score is a questionnaire that allows participants to self-report their chronic conditions and then assess the degree to which each condition interferes with daily activities.
Time frame: From the first dose of study drug to Week 52
Population: Data for this outcome measure was not collected due to the change in planned analysis.
Secondary
Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c)
Baseline was defined as the last non-missing assessment prior to the first dose of study drug. Randomized treatment period: The Month 3 value was defined as Week 13, Month 6 value was defined as Week 26, Month 9 value was defined as Week 38 and Month 12 value was defined as Week 52.
Time frame: Baseline, Months 3, 6, 9, and 12
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 3 | -0.51 percentage of HbA1c |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 6 | 0.06 percentage of HbA1c |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 9 | 0.68 percentage of HbA1c |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 12 | 0.48 percentage of HbA1c |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 12 | 0.28 percentage of HbA1c |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 3 | -0.21 percentage of HbA1c |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 9 | 0.48 percentage of HbA1c |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c) | Change at Month 6 | 0.26 percentage of HbA1c |
Comparison: Month 3p-value: 0.410895% CI: [-0.43, 1.03]ANCOVA
Comparison: Month 6p-value: 0.730895% CI: [-0.95, 1.34]ANCOVA
Comparison: Month 9p-value: 0.751195% CI: [-1.45, 1.06]ANCOVA
Comparison: Month 12p-value: 0.765995% CI: [-1.52, 1.13]ANCOVA
Secondary
Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS)
EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A negative change from baseline indicates worsening. A positive change from baseline indicates improvement.
Time frame: Baseline, Weeks 13, 26 and 52
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 13 | 0.05 score on a scale | Standard Deviation 0.1 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 26 | -0.11 score on a scale | Standard Deviation 0.19 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 52 | -0.08 score on a scale | Standard Deviation 0.1 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 13 | -2 score on a scale | Standard Deviation 13 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 26 | -11 score on a scale | Standard Deviation 17 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 52 | -13 score on a scale | Standard Deviation 18 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 26 | -2 score on a scale | Standard Deviation 14 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 13 | -0.02 score on a scale | Standard Deviation 0.06 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 13 | -2 score on a scale | Standard Deviation 15 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 26 | -0.02 score on a scale | Standard Deviation 0.12 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | EQ VAS Score: Change at Week 52 | -4 score on a scale | Standard Deviation 16 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS) | Index Score: Change at Week 52 | -0.05 score on a scale | Standard Deviation 0.07 |
Secondary
Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores
The SF-36 Health Survey is a 36-item, patient-reported survey of patient health. SF-36 consists of 8 health dimensions,which are weighted sums of the questions in each section. SF-36 included 36 questions related to 8 health dimensions:physical functioning, physical role functioning, bodily pain, general health perceptions, vitality, social role functioning,emotional role functioning, and mental health. Each dimension was scored on a scale of 0 to 100 where, higher score = better quality of life. A positive change from Baseline indicates improvement.
Time frame: Baseline, Weeks 13, 26 and 52
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, number analyzed signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 52 | -0.29 score on a scale | Standard Deviation 6.35 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 52 | -0.85 score on a scale | Standard Deviation 6.11 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 13 | -0.29 score on a scale | Standard Deviation 4.81 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 52 | -3.55 score on a scale | Standard Deviation 4.05 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 13 | -0.46 score on a scale | Standard Deviation 7.97 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 26 | -1.98 score on a scale | Standard Deviation 12.24 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 13 | -1.14 score on a scale | Standard Deviation 7.33 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 13 | -0.55 score on a scale | Standard Deviation 5.57 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 26 | -1.59 score on a scale | Standard Deviation 5 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 52 | -1.50 score on a scale | Standard Deviation 6.74 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 13 | -0.52 score on a scale | Standard Deviation 5.44 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 26 | -2.06 score on a scale | Standard Deviation 10.81 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 52 | -0.32 score on a scale | Standard Deviation 2.02 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning: Change at Week 13 | -1.88 score on a scale | Standard Deviation 4.63 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning: Change at Week 26 | -2.90 score on a scale | Standard Deviation 6.44 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 13 | -3.86 score on a scale | Standard Deviation 9.85 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 26 | -5.01 score on a scale | Standard Deviation 9.07 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 13 | 0.00 score on a scale | Standard Deviation 6.67 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 26 | -2.18 score on a scale | Standard Deviation 7.71 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 52 | -0.37 score on a scale | Standard Deviation 6.66 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 26 | -0.25 score on a scale | Standard Deviation 9 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 26 | -0.64 score on a scale | Standard Deviation 6.49 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning : Change at Week 52 | -1.00 score on a scale | Standard Deviation 5.94 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 52 | 2.87 score on a scale | Standard Deviation 4.89 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 26 | 1.05 score on a scale | Standard Deviation 6.76 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 52 | -2.00 score on a scale | Standard Deviation 7.05 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 52 | -3.30 score on a scale | Standard Deviation 8.2 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning: Change at Week 26 | 0.23 score on a scale | Standard Deviation 7.5 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 13 | -0.41 score on a scale | Standard Deviation 3.91 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 26 | 0.51 score on a scale | Standard Deviation 5.29 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning: Change at Week 13 | 0.75 score on a scale | Standard Deviation 6.85 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Functioning: Change at Week 52 | -2.76 score on a scale | Standard Deviation 5.25 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 52 | -1.75 score on a scale | Standard Deviation 6.13 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 13 | 0.75 score on a scale | Standard Deviation 6.26 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Emotional Role Functioning : Change at Week 52 | -5.42 score on a scale | Standard Deviation 5.8 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 26 | 0.19 score on a scale | Standard Deviation 4.27 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 13 | -0.21 score on a scale | Standard Deviation 5.64 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Bodily Pain: Change at Week 52 | -2.55 score on a scale | Standard Deviation 8.48 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 13 | 1.07 score on a scale | Standard Deviation 4.02 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 13 | -0.58 score on a scale | Standard Deviation 4.04 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 52 | -2.79 score on a scale | Standard Deviation 7.14 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 26 | 0.54 score on a scale | Standard Deviation 7.25 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Vitality: Change at Week 26 | -0.79 score on a scale | Standard Deviation 6.89 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | General Health Perceptions: Change at Week 52 | -1.48 score on a scale | Standard Deviation 4.53 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Mental Health: Change at Week 13 | -0.19 score on a scale | Standard Deviation 7.91 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 13 | -0.64 score on a scale | Standard Deviation 4.61 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Social Role Functioning: Change at Week 26 | -0.67 score on a scale | Standard Deviation 3.21 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores | Physical Role Functioning: Change at Week 26 | 0.75 score on a scale | Standard Deviation 4.7 |
Secondary
Randomized Treatment Period: Patient-Reported Hunger
Patient-reported hunger was assessed by participants who completed a questionnaire about: how hungry you feel, how satisfied you feel, how full you feel, how much you think you can eat, like to eat something sweet, like to eat something salty, like to eat something savory and like to eat something fatty. Participants also rated the palatability of meals that included visual appeal, smell, taste, and aftertaste. Scores of 1-39 were categorized as mild, 40-69 as moderate, and 70-100 as severe. The scores from each assessment time point were averaged for all of the below reported categories.
Time frame: From the first dose of study drug up to Week 52
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | How Full You Feel | 62.6 score on a scale | Standard Deviation 20.5 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Fatty | 77.9 score on a scale | Standard Deviation 18.4 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Sweet | 71.0 score on a scale | Standard Deviation 20.8 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Visual Appeal | 28.6 score on a scale | Standard Deviation 20.5 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | How Satisfied You Feel | 56.8 score on a scale | Standard Deviation 22.4 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Smell | 23.4 score on a scale | Standard Deviation 16.2 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Salty | 66.9 score on a scale | Standard Deviation 21.7 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Taste | 25.5 score on a scale | Standard Deviation 18.3 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Aftertaste | 58.9 score on a scale | Standard Deviation 27.5 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | How Much You Think You Can Eat | 33.6 score on a scale | Standard Deviation 22.1 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Palatability | 31.3 score on a scale | Standard Deviation 20.1 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Savory | 65.2 score on a scale | Standard Deviation 21.4 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Hunger | How Hungry You Feel | 29.4 score on a scale | Standard Deviation 20.7 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Taste | 29.1 score on a scale | Standard Deviation 14.5 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | How Hungry You Feel | 29.6 score on a scale | Standard Deviation 14.4 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | How Satisfied You Feel | 57.5 score on a scale | Standard Deviation 15.1 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | How Full You Feel | 56.6 score on a scale | Standard Deviation 18.4 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | How Much You Think You Can Eat | 36.8 score on a scale | Standard Deviation 15.4 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Sweet | 54.8 score on a scale | Standard Deviation 27.1 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Salty | 69.0 score on a scale | Standard Deviation 20.2 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Savory | 66.8 score on a scale | Standard Deviation 21.9 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Like to Eat Something Fatty | 75.9 score on a scale | Standard Deviation 22.2 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Visual Appeal | 34.5 score on a scale | Standard Deviation 21 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Smell | 25.4 score on a scale | Standard Deviation 15.5 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Aftertaste | 51.0 score on a scale | Standard Deviation 24.6 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Hunger | Palatability | 32.2 score on a scale | Standard Deviation 15.1 |
Secondary
Randomized Treatment Period: Patient-Reported Pain
Patient-reported pain was assessed by rating pain symptoms at its worst and least for the last 24 hours, on average, and at the moment, with 0 as the lowest score (no pain) and 10 as the highest score (worst pain as you can imagine). Patient-reported pain was also assessed by rating pain symptoms (rate pain on average, rate pain right now) that interfered with general activity, interfered with mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life, with 0 as the lowest score (did not interfered) and 10 as the highest score (completely interfered). The scores from each assessment time point were averaged for all of the below reported categories.
Time frame: From the first dose of study drug up to Week 52
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Rate Pain Right Now | 2.72 score on a scale | Standard Deviation 2.59 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Walking Ability | 2.35 score on a scale | Standard Deviation 2.96 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Rate Pain on Average | 3.08 score on a scale | Standard Deviation 2.62 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Normal Work | 2.37 score on a scale | Standard Deviation 2.84 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | General Activity | 2.43 score on a scale | Standard Deviation 2.8 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Relations With Other People | 2.23 score on a scale | Standard Deviation 2.79 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Rate Pain at its Least Last 24 Hours | 2.45 score on a scale | Standard Deviation 2.46 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Sleep | 2.75 score on a scale | Standard Deviation 2.95 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Interfere With Mood | 2.31 score on a scale | Standard Deviation 2.88 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Enjoyment of Life | 2.42 score on a scale | Standard Deviation 2.82 |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Patient-Reported Pain | Rate Pain at its Worst Last 24 Hours | 3.28 score on a scale | Standard Deviation 2.79 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Enjoyment of Life | 2.68 score on a scale | Standard Deviation 2.62 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Rate Pain at its Worst Last 24 Hours | 3.57 score on a scale | Standard Deviation 2.72 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Rate Pain at its Least Last 24 Hours | 2.59 score on a scale | Standard Deviation 2.43 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Rate Pain on Average | 3.16 score on a scale | Standard Deviation 2.47 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Rate Pain Right Now | 2.96 score on a scale | Standard Deviation 2.5 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | General Activity | 2.83 score on a scale | Standard Deviation 2.57 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Interfere With Mood | 2.98 score on a scale | Standard Deviation 2.59 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Walking Ability | 2.79 score on a scale | Standard Deviation 2.59 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Normal Work | 2.89 score on a scale | Standard Deviation 2.56 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Relations With Other People | 2.62 score on a scale | Standard Deviation 2.67 |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Patient-Reported Pain | Sleep | 2.73 score on a scale | Standard Deviation 2.75 |
Secondary
Randomized Treatment Period: Percentage of Participants Who Achieved Greater Than or Equal to (≥) 40% Reduction in Fasting Triglyceride and ≥ 30% Reduction of Hepatic Fat Fraction at Month 6
The baseline of TG is defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. The baseline of hepatic fat fraction is defined as the last non-missing assessment prior to the first dose of study drug. Randomized treatment period: Month 6 value was defined as average of Week 25 and Week 26 for fasting TG and Week 25 or Week 26 for hepatic fat fraction.
Time frame: Month 6
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment. This outcome measure is reported here for the randomized treatment period only, as per the planned analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Percentage of Participants Who Achieved Greater Than or Equal to (≥) 40% Reduction in Fasting Triglyceride and ≥ 30% Reduction of Hepatic Fat Fraction at Month 6 | 5.3 percentage of participants |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Percentage of Participants Who Achieved Greater Than or Equal to (≥) 40% Reduction in Fasting Triglyceride and ≥ 30% Reduction of Hepatic Fat Fraction at Month 6 | 42.9 percentage of participants |
Secondary
Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI)
Baseline was defined as the last non-missing assessment prior to the first dose of study drug in the randomized treatment period. Randomized treatment period: Month 6 value was defined as Week 25 or Week 26 for MRI assessment and Month 12 was defined as Week 50 or Week 52 for MRI assessment. Hepatic steatosis is a reversible condition in which large vacuoles of triglyceride fat accumulate in the liver cells, causing nonspecific inflammation. Hepatic Steatosis was assessed by hepatic fat fraction using MRI.
Time frame: Baseline, Months 6 and 12
Population: FAS included all participants who were randomized and received at least one dose of study drug in the randomized treatment period, and who had a baseline fasting TG assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI) | Percent Change at Month 6 | 2.83 percent change |
| Randomized Treatment Period: Placebo | Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI) | Percent Change at Month 12 | 1.46 percent change |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI) | Percent Change at Month 6 | -22.86 percent change |
| Randomized Treatment Period: Volanesorsen | Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI) | Percent Change at Month 12 | -51.87 percent change |
Comparison: Month 6p-value: 0.073695% CI: [-54.03, 2.65]ANCOVA
Comparison: Month 12p-value: 0.003995% CI: [-87.71, -18.95]ANCOVA