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

Overview

  • Study type

    Interventional
  • Study phase

    II/III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 15-004679
    NCT ID: NCT02527343
    Sponsor Protocol Number: ISIS 304801-CS17

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Clinical diagnosis of FPL plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia.
  • Diagnosis of FLP 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:
  • Genetic diagnosis of familial PL (e.g., mutations in LMNA, PPAR-γ, AKT2, CIDEC, PLIN1 genes)

OR

-Family history of FPL or family history of abnormal and similar fat distribution plus 1 Minor Criteria

OR

-2 Minor Criteria (In the absence of FPL-associated genetic variant or family history) and BMI< 35 kg/m2

Minor Criteria

  1. Requirement for high doses of insulin, e.g., requiring ≥ 200 U/day, ≥ 2 U/kg/day, or currently taking U-500 insulin
  2. Presence of acanthosis nigricans on physical examination
  3. Evidence/history of polycystic ovary syndrome (PCOS) or PCOS-like symptoms (hirsutism, oligomenorrhea, and/or polycystic ovaries)
  4. History of pancreatitis associated with hypertriglyceridemia
  5. Evidence of non-alcoholic fatty liver disease
    • Hepatomegaly and/or elevated transaminases in the absence of a known cause of liver disease or radiographic evidence of hepatic steatosis (e.g., on ultrasound or CT)
    • Diagnosis of Type 2 diabetes mellitus as defined by the American Diabetes Association Standards of Medical Care in Diabetes 2015) made at least 12 weeks prior to the Screening visit, and 2 of the following:
      • on standard-of-care anti-diabetic therapy, and
      • HbA1c ≥ 7% to ≤ 10% at Screening.
    • Hypertriglyceridemia is defined as Fasting TG levels ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening and Qualification visit.
      • If the fasting TG value at Screening and/or Qualification visit is < 500 mg/dL (< 5.7 mmol/L) but ≥ 350 mg/dL (≥ 4.0 mmol/L) up to 2 additional tests may be performed in order to qualify

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 ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack, or unstable congestive heart failure requiring a change in medication
    • Major surgery within 3 months of Screening
    • Treatment with Metreleptin within the last 3 months prior to Screening
    • Previous treatment with ISIS-APOCIIIRx

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Vinaya Simha, M.B.B.S., M.D.

Open for enrollment

Contact information:

Tamera Roberson

(507)255-8621

Roberson.Tamera@mayo.edu