Clinical trial NCT02211209: The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Familial Chylomicronemia Syndrome
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Akcea Therapeutics
First posted: 2014-08-07
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3
timeFrame: Baseline to 3 months
Secondary outcomes:
measure: Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)
timeFrame: Baseline to an on-treatment assessment between Week 13 and Week 19
measure: Absolute Change From Baseline in Fasting TG at Month 3
timeFrame: Baseline to 3 months
measure: Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3
timeFrame: Baseline to 3 months
measure: Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3
timeFrame: Baseline to 3 months
measure: Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period
timeFrame: Baseline to 12 months
measure: Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period
timeFrame: 12 months
measure: Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: IONIS Investigative Site
state: California
city: San Francisco
country: United States
facility: IONIS Investigative Site
state: California
city: Kansas City
country: United States
facility: IONIS Investigative Site
state: Kansas
city: Boston
country: United States
facility: IONIS Investigative Site
state: Massachusetts
city: New York
country: United States
facility: IONIS Investigative Site
state: New York
city: Oklahoma City
country: United States
facility: IONIS Investigative Site
state: Oklahoma
city: Portland
country: United States
facility: IONIS Investigative Site
state: Oregon
city: Philadelphia
country: United States
facility: IONIS Investigative Site
state: Pennsylvania
city: Houston
country: United States
facility: IONIS Investigative Site
state: Texas
city: Norfolk
country: United States
facility: IONIS Investigative Site
state: Virginia
city: Seattle
country: United States
facility: IONIS Investigative Site
state: Washington
city: Campinas
country: Brazil
facility: IONIS Investigative Site
city: Sao Paulo
country: Brazil
facility: IONIS Investigative Site
city: Sao Paulo
country: Brazil
facility: IONIS Investigative Site
city: Vancouver
country: Canada
facility: IONIS Investigative Site
state: British Columbia
city: Chicoutimi
country: Canada
facility: IONIS Investigative Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: IONIS Investigative Site
state: Quebec
city: Marseille
country: France
facility: IONIS Investigative Site
city: Nantes
country: France
facility: IONIS Investigative Site
city: Paris
country: France
facility: IONIS Investigative Site
city: Berlin
country: Germany
facility: IONIS Investigative Site
city: Dresden
country: Germany
facility: IONIS Investigative Site
city: Szikszo
country: Hungary
facility: IONIS Investigative Site
city: Safed
country: Israel
facility: IONIS Investigative Site
city: Milan
country: Italy
facility: IONIS Investigative Site
city: Palermo
country: Italy
facility: IONIS Investigative Site
city: Rome
country: Italy
facility: IONIS Investigative Site
city: Amsterdam
country: Netherlands
facility: IONIS Investigative Site
city: Rotterdam
country: Netherlands
facility: IONIS Investigative Site
city: Cape Town
country: South Africa
facility: IONIS Investigative Site
city: Zaragoza
country: Spain
facility: IONIS Investigative Site
state: Aragon
city: La Coruna
country: Spain
facility: IONIS Investigative Site
state: Galicia
city: Barcelona
country: Spain
facility: IONIS Investigative Site
city: Madrid
country: Spain
facility: IONIS Investigative Site
city: Malaga
country: Spain
facility: IONIS Investigative Site
city: Sevilla
country: Spain
facility: IONIS Investigative Site
city: Birmingham
country: United Kingdom
facility: IONIS Investigative Site
city: Manchester
country: United Kingdom
facility: IONIS Investigative Site
city: Manchester
country: United Kingdom
facility: IONIS Investigative Site
city: Peterborough
country: United Kingdom
facility: IONIS Investigative Site
Study officials:
References:
citation: 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 Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944.
citation: Hegele RA, Berberich AJ, Ban MR, Wang J, Digenio A, Alexander VJ, D'Erasmo L, Arca M, Jones A, Bruckert E, Stroes ES, Bergeron J, Civeira F, Witztum JL, Gaudet D. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018 Jul-Aug;12(4):920-927.e4. doi: 10.1016/j.jacl.2018.03.093. Epub 2018 Apr 4.
citation: Digenio A, Dunbar RL, Alexander VJ, Hompesch M, Morrow L, Lee RG, Graham MJ, Hughes SG, Yu R, Singleton W, Baker BF, Bhanot S, Crooke RM. Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes. Diabetes Care. 2016 Aug;39(8):1408-15. doi: 10.2337/dc16-0126. Epub 2016 Jun 6.