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

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