The BROADEN Study: A Study of Volanesorsen (Formerly ISIS-APOCIIIRx) in Patients With Familial Partial Lipodystrophy


The purpose of this study is to evaluate the efficacy and safety of volanesorsen (IONIS-APOCIIIRx) given for 52 weeks in patients with Familial Partial Lipodystrophy. Patients will then be allowed to continue in a 2 year Open Label Extension of the study.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: June 30, 2018


  • Drug: volanesorsen
  • Drug: Placebo

Arms, Groups and Cohorts

  • Active Comparator: volanesorsen 300mg
    • volanesorsen administered subcutaneously once weekly for 52 weeks
  • Placebo Comparator: Placebo
    • Placebo administered subcutaneously once weekly for 52 weeks.
  • Active Comparator: Open Label Extension (OLE)
    • Volanesorsen administered subcutaneously once weekly for 104 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Efficacy of volanesorsen (IONIS-APOCIIIRx) measured as the percent change in fasting triglycerides from baseline.
    • Time Frame: 13 weeks

Secondary Measures

  • Change from Baseline in hepatic steatosis (as assessed by hepatic fat fraction using magnetic resonance imaging (MRI).
    • Time Frame: 52 weeks
  • Change from Baseline in hemoglobin A1c (HbA1c)
    • Time Frame: 52 weeks
  • A composite endpoint at Month 6 for percent of patients who achieve a. ≥ 40% reduction in fasting TG, and b. ≥ 30% reduction of hepatic fat fraction percent
    • Time Frame: 52 weeks
  • Change in patient-reported outcomes (PRO)
    • Time Frame: 52 weeks

Participating in This Clinical Trial

Inclusion Criteria

  • Must give written informed consent to participate in the study (signed and dated) and any authorizations required by law – Clinical diagnosis of 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 (≤ 10 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 BMI< 35 kg/m2 – Diabetes not well controlled on antidiabetic therapy with HbA1c ≥ 7% to ≤ 12% at Screening – Hypertriglyceridemia with Fasting TG levels ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening and Qualification visit, or Fasting TG levels ≥ 200 (≥ 2.26 mmol/L) at both Screening and Qualification Visits for patients who meet the genetic or family history criteria – Presence of hepatosteatosis (fatty liver), as evidenced by a Screening 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 – LDL-C > 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ionis Pharmaceuticals, Inc.
  • Collaborator
    • Akcea Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor

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