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

Overview

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

Interventions

  • 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

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.