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 3
  • Study Type

    Interventional
  • Study Participants

    67
The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in participants with Familial Chylomicronemia Syndrome
Study Started
Dec 31
2014
Primary Completion
Dec 19
2016
Study Completion
Mar 28
2017
Results Posted
Apr 13
2022
Last Update
Apr 13
2022

Drug Volanesorsen

  • Other names: ISIS 304801, ApoC-III, Approach, IONIS-APOCIIIRx

Drug Placebo

Placebo Placebo Comparator

Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.

Volanesorsen Experimental

Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.

Criteria

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

Summary

Placebo

Volanesorsen

All Events

Event Type Organ System Event Term Placebo Volanesorsen

Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3

The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.

Placebo

17.6
percent change (Least Squares Mean)
95% Confidence Interval: -4.0 to 39.2

Volanesorsen

-76.5
percent change (Least Squares Mean)
95% Confidence Interval: -97.4 to -55.5

Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)

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.

Placebo

36.92
millimole hours per liter (mmol*h/L) (Mean)
Standard Deviation: 121.54

Volanesorsen

-234.77
millimole hours per liter (mmol*h/L) (Mean)
Standard Deviation: 94.86

Absolute Change From Baseline in Fasting TG at Month 3

The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.

Placebo

92.0
mg/dL (Least Squares Mean)
95% Confidence Interval: -301.0 to 486.0

Volanesorsen

-1712.0
mg/dL (Least Squares Mean)
95% Confidence Interval: -2094.0 to -1330.0

Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3

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

Placebo

3.0
participants

Volanesorsen

23.0
participants

Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3

The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.

Placebo

3.0
participants

Volanesorsen

29.0
participants

Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period

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.

Placebo

Mild

1.0
participants

Moderate

5.0
participants

No pain

19.0
participants

Severe

8.0
participants

Volanesorsen

Mild

4.0
participants

Moderate

6.0
participants

No pain

18.0
participants

Severe

5.0
participants

Change From Baseline in Hepatosplenomegaly as Assessed by MRI at 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.

Placebo

-25.0
cubic centimeters (cm^3) (Least Squares Mean)
95% Confidence Interval: -150.0 to 100.0

Volanesorsen

113.0
cubic centimeters (cm^3) (Least Squares Mean)
95% Confidence Interval: -43.0 to 269.0

Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period

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.

Placebo

2.04
events per participant per year (Mean)
Standard Deviation: 4.28

Volanesorsen

2.73
events per participant per year (Mean)
Standard Deviation: 6.57

Total

66
Participants

Age, Continuous

46
years (Mean)
Standard Deviation: 13

Fasting Triglycerides

2209
milligrams per deciliter (mg/dL) (Mean)
Standard Deviation: 1199

Race/Ethnicity, Customized

Region of Enrollment

Sex: Female, Male

Overall Study

Placebo

Volanesorsen

Drop/Withdrawal Reasons

Placebo

Volanesorsen