The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome

Familial Chylomicronemia Syndrome Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211209
• Other study ID #: ISIS 304801-CS6
• Secondary ID: 2014-002421-35
• Status: Completed
• Phase: Phase 3
• Start date: December 2014
• Est. completion date: March 28, 2017

Study information

• Verified date: March 2022
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 28, 2017
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Chylomicronemia Syndrome
• Hyperlipoproteinemia Type I
• Syndrome

Intervention

Drug:
• Volanesorsen

• Placebo

Locations

Country	Name	City	State
Brazil	IONIS Investigative Site	Campinas
Brazil	IONIS Investigative Site	Sao Paulo
Brazil	IONIS Investigative Site	Sao Paulo
Canada	IONIS Investigative Site	Chicoutimi	Quebec
Canada	IONIS Investigative Site	Sainte-Foy	Quebec
Canada	IONIS Investigative Site	Vancouver	British Columbia
France	IONIS Investigative Site	Marseille
France	IONIS Investigative Site	Nantes
France	IONIS Investigative Site	Paris
Germany	IONIS Investigative Site	Berlin
Germany	IONIS Investigative Site	Dresden
Hungary	IONIS Investigative Site	Szikszo
Israel	IONIS Investigative Site	Safed
Italy	IONIS Investigative Site	Milan
Italy	IONIS Investigative Site	Palermo
Italy	IONIS Investigative Site	Rome
Netherlands	IONIS Investigative Site	Amsterdam
Netherlands	IONIS Investigative Site	Rotterdam
South Africa	IONIS Investigative Site	Cape Town
Spain	IONIS Investigative Site	Barcelona
Spain	IONIS Investigative Site	La Coruna	Galicia
Spain	IONIS Investigative Site	Madrid
Spain	IONIS Investigative Site	Malaga
Spain	IONIS Investigative Site	Sevilla
Spain	IONIS Investigative Site	Zaragoza	Aragon
United Kingdom	IONIS Investigative Site	Birmingham
United Kingdom	IONIS Investigative Site	Manchester
United Kingdom	IONIS Investigative Site	Manchester
United Kingdom	IONIS Investigative Site	Peterborough
United States	IONIS Investigative Site	Boston	Massachusetts
United States	IONIS Investigative Site	Encinitas	California
United States	IONIS Investigative Site	Houston	Texas
United States	IONIS Investigative Site	Kansas City	Kansas
United States	IONIS Investigative Site	New York	New York
United States	IONIS Investigative Site	Norfolk	Virginia
United States	IONIS Investigative Site	Oklahoma City	Oklahoma
United States	IONIS Investigative Site	Philadelphia	Pennsylvania
United States	IONIS Investigative Site	Portland	Oregon
United States	IONIS Investigative Site	San Francisco	California
United States	IONIS Investigative Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.	Akcea Therapeutics

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  South Africa,  Spain,  United Kingdom, 

References & Publications (1)

Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familia

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to 3 months
Secondary	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.	Baseline to an on-treatment assessment between Week 13 and Week 19
Secondary	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.	Baseline to 3 months
Secondary	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	Baseline to 3 months
Secondary	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.	Baseline to 3 months
Secondary	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.	Baseline to 12 months
Secondary	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.	12 months
Secondary	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.	Baseline to Week 52