Familial Partial LipodystrophyPhase 2/3NCT02527343
The BROADEN Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Partial Lipodystrophy
A Phase 2/3 study testing volanesorsen in people with Familial Partial Lipodystrophy, run by Akcea Therapeutics at 12 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Partial Lipodystrophy
- What is being tested?
- volanesorsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 12 sitesin 7 countries
- Study dates
- 28 Dec 2015to 13 Nov 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Genetic diagnosis of FPL OR
- Family history of FPL or of similar abnormal fat distribution plus 1 Minor Criteria OR
- 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).
Show all 9Show fewer
- 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%.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 7 countries.
12 sites in 7 countries
United States6 sites
IONIS Investigative Site
Ann Arbor, Michigan, 48105
IONIS Investigative Site
Dallas, Texas, 75390
IONIS Investigative Site
Morehead City, North Carolina, 28557
IONIS Investigative Site
Philadelphia, Pennsylvania, 19104
IONIS Investigative Site
Rochester, Minnesota, 55905
IONIS Investigative Site
St Louis, Missouri, 63110
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, With an Open Label Extension, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Partial Lipodystrophy
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.
- Conditions
- Familial Partial Lipodystrophy
- Being tested
- volanesorsen, Placebo
- Medical subject headings
- Lipodystrophy, Familial Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
volanesorsenDrug
Also called ISIS 304801, IONIS-APOCIIIRx
300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW).
PlaceboDrug
Volanesorsen-matching placebo administered SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Volanesorsen | Experimental | Randomized Period: Volanesorsen-matching placebo as SC, QW for Weeks 1-52. Participants who received volanesorsen-matching placebo in RT period and not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed.
OLE Period: Participants who received volanesorsen-matching placebo in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Weeks 105-156). Participants not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE. Receives: Drug: volanesorsen; Drug: Placebo |
| Volanesorsen | Experimental | Randomized Period: 300 mg of volanesorsen as SC, QW for Weeks 1-52. Participants who received 300 mg of volanesorsen in RT period and did not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed.
OLE Period: Participants who received volanesorsen in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Week 105-156). Participants who were not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE. Receives: Drug: volanesorsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Month 3
Secondary outcomes (15)
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.
Measured: Baseline, Months 6 and 12
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.
Measured: Baseline, Months 6 and 12
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.
Measured: Baseline, Months 3, 6, 9, and 12
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.
Measured: Baseline, Months 3, 6, 9, and 12
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.
Measured: Month 6
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.
Measured: From the first dose of study drug to Week 52
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.
Measured: From the first dose of study drug in open label extension period to Week 117
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.
Measured: From the first dose of study drug up to Week 52
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.
Measured: From the first dose of study drug in open label extension period up to Week 117
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.
Measured: From the first dose of study drug up to Week 52
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.
Measured: From the first dose of study drug in open label extension period up to Week 117
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.
Measured: Baseline, Weeks 13, 26 and 52
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.
Measured: Baseline, Weeks 65, 78 and 104
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.
Measured: Baseline, Weeks 13, 26 and 52
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.
Measured: Baseline, Weeks 65, 78 and 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2015 (estimated)
- Study start28 Dec 2015
- Primary completion30 Jun 2018
- Study completion13 Nov 2019
Why it stopped: Study terminated early at a time point when sufficient data had been accumulated to inform a decision on further development of volanesoresen in participants with FPL.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial Partial LipodystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akcea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527343
- Sponsor's protocol ID
- ISIS 304801-CS17
- Other IDs
- 2015-000493-35, 2015
- Status last verified
- Sep 2021
- First submitted
- 17 Aug 2015
- Last updated
- 18 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
Prohaska TA, Alexander VJ, Karwatowska-Prokopczuk E, Tami J, Xia S, Witztum JL, Tsimikas S. APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. J Clin Lipidol. 2023 May-Jun;17(3):406-411. doi: 10.1016/j.jacl.2023.04.007. Epub 2023 Apr 27.
PubMed 37164837
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, With an Open Label Extension, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Partial Lipodystrophy
- ClinicalTrials.gov ID
- NCT02527343
- Acronym / sponsor ID
- ISIS 304801-CS17
- Conditions
- Familial Partial Lipodystrophy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early at a time point when sufficient data had been accumulated to inform a decision on further development of volanesoresen in participants with FPL.
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Akcea TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- 28 Dec 2015 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 13 Nov 2019 (actual)
- First posted
- 19 Aug 2015 (estimated)
- Results
- Posted 18 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo/Volanesorsen | Experimental | Drug: volanesorsen, Drug: PlaceboRandomized Period: Volanesorsen-matching placebo as SC, QW for Weeks 1-52. Participants who received volanesorsen-matching placebo in RT period and not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed. OLE Period: Participants who received volanesorsen-matching placebo in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Weeks 105-156). Participants not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE. |
| Volanesorsen | Experimental | Drug: volanesorsenRandomized Period: 300 mg of volanesorsen as SC, QW for Weeks 1-52. Participants who received 300 mg of volanesorsen in RT period and did not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed. OLE Period: Participants who received volanesorsen in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Week 105-156). Participants who were not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| volanesorsenAlso: ISIS 304801, IONIS-APOCIIIRx300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW). | Drug | Placebo/Volanesorsen, Volanesorsen |
| PlaceboVolanesorsen-matching placebo administered SC injection. | Drug | Placebo/Volanesorsen |
Primary outcome
Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
Time frame: 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.
15 secondary outcomes
Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Months 6 and 12
Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI
Time frame: Baseline, Months 6 and 12
Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c)
Time frame: Baseline, Months 3, 6, 9, and 12
Open Label Extension Period: Change From Baseline in HbA1c
Time frame: Baseline, Months 3, 6, 9, and 12
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
Time frame: Month 6
Randomized Treatment Period: Change From Baseline in Disease Burden Score
Time frame: From the first dose of study drug to Week 52
Open-Label Extension Period: Change From Baseline in Disease Burden Score
Time frame: From the first dose of study drug in open label extension period to Week 117
Randomized Treatment Period: Patient-Reported Pain
Time frame: From the first dose of study drug up to Week 52
Open Label Extension Period: Patient-Reported Pain
Time frame: From the first dose of study drug in open label extension period up to Week 117
Randomized Treatment Period: Patient-Reported Hunger
Time frame: From the first dose of study drug up to Week 52
Open Label Extension Period: Patient-Reported Hunger
Time frame: From the first dose of study drug in open label extension period up to Week 117
Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores
Time frame: Baseline, Weeks 13, 26 and 52
Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores
Time frame: Baseline, Weeks 65, 78 and 104
Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS)
Time frame: Baseline, Weeks 13, 26 and 52
Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores
Time frame: Baseline, Weeks 65, 78 and 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37164837Prohaska TA, Alexander VJ, Karwatowska-Prokopczuk E, Tami J, Xia S, Witztum JL, Tsimikas S. APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. J Clin Lipidol. 2023 May-Jun;17(3):406-411. doi: 10.1016/j.jacl.2023.04.007. Epub 2023 Apr 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing volanesorsen in people with Familial Partial Lipodystrophy, run by Akcea Therapeutics at 12 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Belgium, Brazil, Canada, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) (time frame: Baseline to Month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02527343, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.