Title
The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Phase
Phase 3Lead Sponsor
Ionis Pharmaceuticals, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Familial Chylomicronemia SyndromeIntervention/Treatment
volanesorsen sodium ...Study Participants
67The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in participants with Familial Chylomicronemia Syndrome
Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.
Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.
Inclusion Criteria: History of chylomicronemia A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia) Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening Exclusion Criteria: Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0% Other types of severe hypertriglyceridemia Active pancreatitis within 4 weeks of screening Acute Coronary Syndrome within 6 months of screening Major surgery within 3 months of screening Treatment with Glybera therapy within 2 years of screening Previous treatment with IONIS-APOCIIIRx Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study
| Event Type | Organ System | Event Term | Placebo | Volanesorsen |
|---|
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.
Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.
The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.
