Study of ISIS 304801 versus placebo Administered Subcutaneously to Patients with Partial Lipodystrophy

A Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients with Partial Lipodystrophy - The BROADEN Study

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-000493-35-ES

Enrollment

125

Registered

2015-10-15

Start date

2015-12-04

Completion date

Unknown

Last updated

2018-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Partial lipodystrophy MedDRA version: 18.1 Level: PT Classification code 10053857 Term: Partial lipodystrophy System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Interventions

Product Name: VOLANESORSEN SODIUM, ApoC-III Antisense Oligonucleotide Product Code: ISIS 304801 Pharmaceutical Form: Solution for injection INN or Proposed INN: ISIS 304801 CAS Number: 915430-78-3 Cur

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Clinical diagnosis of partial lipodystrophy based on deficiency of subcutaneous body fat in a partial fashion assessed by physical examination, and at least one (1) MAJOR criterion and one (1) MINOR criterion (below): MAJOR Criteria a. Low skinfold thickness in anterior thigh by caliper measurement: men (? 10 mm) and women (? 22 mm) OR b. Genetic diagnosis of familial PL (e.g., mutations in LMNA, PPAR-?, AKT2, PLIN1 genes) MINOR Criteria a. Insulin resistance defined as fasting insulin ? 20 mcU/mL b. Diabetes mellitus c. Acanthosis nigricans d. Polycystic ovary syndrome (PCOS) or PCOS-like symptoms (hirsutism, oligomenorrhea, and/or polycystic ovaries) e. History of pancreatitis associated with hypertriglyceridemia f. History of hepatic steatosis or steatohepatitis g. Similar fat distribution and/or history of fat loss in a first degree relative h. Prominent muscularity and phlebomegaly (enlarged veins) in the extremities i. Disproportionate hyperphagia 2. Fasting TG ? 500 mg/dL (? 5.7 mmol/L) at Screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3

Exclusion criteria

Exclusion criteria: 1. A diagnosis of generalized lipodystrophy 2. Current or history of autoimmune diseases (even with a diagnosis of PL) unless approved by the Investigator and Sponsor Medical Monitor 3. Acute pancreatitis within 4 weeks of Screening 4. 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 5. Major surgery within 3 months of Screening 6. Previous treatment with ISIS-APOCIII Rx 7. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the percent change in fasting TG from baseline to Month 3.;Secondary Objective: To evaluate the efficacy of ISIS 304801 as compared to placebo on: ? Absolute change from Baseline in fasting TG at 3, 6 and 12 months ? Percent of patients who achieve a ? 40% reduction in fasting TG at 3, 6 and 12 months ? Change from Baseline in hemoglobin A1c (HbA1c) at 6, 9 and 12 months ? Change from Baseline in fasting plasma glucose (FPG) at 6, 9 and 12 months ? Change from Baseline in liver volume and hepatic steatosis (as assessed by magnetic resonance imaging [MRI]) at 6 and 12 months To evaluate the effects of ISIS 304801 as compared to placebo on: ? Safety and tolerability ? Prospectively adjudicated acute pancreatitis events (Atlanta classification) and Major Adverse Cardiovascular Events (MACE);Primary end point(s): The primary efficacy analysis will be the comparison of percent changes from Baseline to the primary analysis time point in fasting TG between ISIS 304801 300 mg once weekly group and placebo group;Timepoint(s) of evaluation of this end point: The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments	—

Measure

Time frame

Main Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the percent change in fasting TG from baseline to Month 3.;Secondary Objective: To evaluate the efficacy of ISIS 304801 as compared to placebo on: ? Absolute change from Baseline in fasting TG at 3, 6 and 12 months ? Percent of patients who achieve a ? 40% reduction in fasting TG at 3, 6 and 12 months ? Change from Baseline in hemoglobin A1c (HbA1c) at 6, 9 and 12 months ? Change from Baseline in fasting plasma glucose (FPG) at 6, 9 and 12 months ? Change from Baseline in liver volume and hepatic steatosis (as assessed by magnetic resonance imaging [MRI]) at 6 and 12 months To evaluate the effects of ISIS 304801 as compared to placebo on: ? Safety and tolerability ? Prospectively adjudicated acute pancreatitis events (Atlanta classification) and Major Adverse Cardiovascular Events (MACE);Primary end point(s): The primary efficacy analysis will be the comparison of percent changes from Baseline to the primary analysis time point in fasting TG between ISIS 304801 300 mg once weekly group and placebo group;Timepoint(s) of evaluation of this end point: The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments

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Secondary

Measure	Time frame
Secondary end point(s): The secondary endpoints include: ? Absolute change from Baseline in fasting TG at 3, 6 and 12 months ? Proportion of patients who achieve a ? 40% reduction in fasting TG at 3, 6 and 12 months ? Change from Baseline in HbA1c at 6, 9 and 12 months ? Change from Baseline in fasting plasma glucose at 6, 9 and 12 months ? Change from Baseline in liver volume and hepatic steatosis (as assessed by MRI) at 6 and 12 months;Timepoint(s) of evaluation of this end point: At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The value at Month 6 is defined as the average of Week 25 and Week 26 and the value at Month 12 is defined as the average of Week 51 and Week 52 fasting assessments.	—

Measure

Time frame

Secondary end point(s): The secondary endpoints include: ? Absolute change from Baseline in fasting TG at 3, 6 and 12 months ? Proportion of patients who achieve a ? 40% reduction in fasting TG at 3, 6 and 12 months ? Change from Baseline in HbA1c at 6, 9 and 12 months ? Change from Baseline in fasting plasma glucose at 6, 9 and 12 months ? Change from Baseline in liver volume and hepatic steatosis (as assessed by MRI) at 6 and 12 months;Timepoint(s) of evaluation of this end point: At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The value at Month 6 is defined as the average of Week 25 and Week 26 and the value at Month 12 is defined as the average of Week 51 and Week 52 fasting assessments.

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Countries

Australia, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Netherlands, Poland, Portugal, Russian Federation, Spain, Turkey, United Kingdom, United States

Contacts

Public ContactMónica Bermejo

Medpace Spain S.L

m.bermejo@medpace.com3491853 4105

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026