The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
- Conditions
- Familial Chylomicronemia Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT02211209
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in participants with Familial Chylomicronemia Syndrome
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
- History of chylomicronemia
- A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia)
- Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks. Volanesorsen Volanesorsen Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.
- Primary Outcome Measures
Name Time Method Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3 Baseline to 3 months The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h) Baseline to an on-treatment assessment between Week 13 and Week 19 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.
Absolute Change From Baseline in Fasting TG at Month 3 Baseline to 3 months The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3 Baseline to 3 months 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
Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3 Baseline to 3 months The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period Baseline to 12 months 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.
Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period 12 months 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.
Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52 Baseline to Week 52 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.
Trial Locations
- Locations (1)
IONIS Investigative Site
🇬🇧Peterborough, United Kingdom