Clinical trial NCT02527343: The BROADEN Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Partial Lipodystrophy
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Familial Partial Lipodystrophy
Lead sponsor: Akcea Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2015-08-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Randomized Treatment Period: Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
timeFrame: Baseline to Month 3
Secondary outcomes:
measure: Randomized Treatment Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Months 6 and 12
measure: Open-Label Extension Period: Percent Change From Baseline in Hepatic Steatosis as Assessed by Hepatic Fat Fraction Using MRI
timeFrame: Baseline, Months 6 and 12
measure: Randomized Treatment Period: Change From Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Open Label Extension Period: Change From Baseline in HbA1c
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Month 6
measure: Randomized Treatment Period: Change From Baseline in Disease Burden Score
timeFrame: From the first dose of study drug to Week 52
measure: Open-Label Extension Period: Change From Baseline in Disease Burden Score
timeFrame: From the first dose of study drug in open label extension period to Week 117
measure: Randomized Treatment Period: Patient-Reported Pain
timeFrame: From the first dose of study drug up to Week 52
measure: Open Label Extension Period: Patient-Reported Pain
timeFrame: From the first dose of study drug in open label extension period up to Week 117
measure: Randomized Treatment Period: Patient-Reported Hunger
timeFrame: From the first dose of study drug up to Week 52
measure: Open Label Extension Period: Patient-Reported Hunger
timeFrame: From the first dose of study drug in open label extension period up to Week 117
measure: Randomized Treatment Period: Change From Baseline in Mean Short Form-36 (SF-36) Weighted Sum of Scores
timeFrame: Baseline, Weeks 13, 26 and 52
measure: Open-Label Extension Period: Change From Baseline in Mean SF-36 Weighted Sum of Scores
timeFrame: Baseline, Weeks 65, 78 and 104
measure: Randomized Treatment Period: Change From Baseline in Mean EQ-5D: Index Scores and Visual Analog Scale (VAS)
timeFrame: Baseline, Weeks 13, 26 and 52
measure: Open-Label Extension Period: Change From Baseline in Mean EQ-5D: Index and Visual Analog Scale (VAS) Scores
timeFrame: Baseline, Weeks 65, 78 and 104
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: IONIS Investigative Site
state: Michigan
city: Rochester
country: United States
facility: IONIS Investigative Site
state: Minnesota
city: Saint Louis
country: United States
facility: IONIS Investigative Site
state: Missouri
city: Morehead City
country: United States
facility: IONIS Investigative Site
state: North Carolina
city: Philadelphia
country: United States
facility: IONIS Investigative Site
state: Pennsylvania
city: Dallas
country: United States
facility: IONIS Investigative Site
state: Texas
city: Leuven
country: Belgium
facility: IONIS Investigative Site
city: Rio de Janeiro
country: Brazil
facility: IONIS Investigative Site
city: Halifax
country: Canada
facility: IONIS Investigative Site
state: Nova Scotia
city: Muenster
country: Germany
facility: IONIS Investigative Site
city: Amsterdam-Zuidoost
country: Netherlands
facility: IONIS Investigative Site
city: Moscow
country: Russian Federation
facility: IONIS Investigative Site
Study officials:
References: