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

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ClinicalTrials.gov Identifier: NCT02211209

Recruitment Status : Completed

First Posted : August 7, 2014

Results First Posted : April 13, 2022

Last Update Posted : April 13, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Akcea Therapeutics

Information provided by (Responsible Party):

Ionis Pharmaceuticals, Inc.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Familial Chylomicronemia Syndrome	Drug: Volanesorsen Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	67 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Actual Study Start Date :	December 2014
Actual Primary Completion Date :	December 19, 2016
Actual Study Completion Date :	March 28, 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial lipoprotein lipase deficiency

MedlinePlus related topics: Family Issues

Genetic and Rare Diseases Information Center resources: Familial Lipoprotein Lipase Deficiency Familial Chylomicronemia Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.	Drug: Placebo
Experimental: Volanesorsen Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.	Drug: Volanesorsen Other Names: ISIS 304801 ApoC-III Approach IONIS-APOCIIIRx

Outcome Measures

Primary Outcome Measures :

Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3 [ Time Frame: 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 :

Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02211209

Locations

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United States, California
IONIS Investigative Site
Encinitas, California, United States, 92024
IONIS Investigative Site
San Francisco, California, United States, 94143
United States, Kansas
IONIS Investigative Site
Kansas City, Kansas, United States, 66214
United States, Massachusetts
IONIS Investigative Site
Boston, Massachusetts, United States, 02114
United States, New York
IONIS Investigative Site
New York, New York, United States, 10016
United States, Oklahoma
IONIS Investigative Site
Oklahoma City, Oklahoma, United States, 73103
United States, Oregon
IONIS Investigative Site
Portland, Oregon, United States, 97239
United States, Pennsylvania
IONIS Investigative Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
IONIS Investigative Site
Houston, Texas, United States, 77030
United States, Virginia
IONIS Investigative Site
Norfolk, Virginia, United States, 23510
United States, Washington
IONIS Investigative Site
Seattle, Washington, United States, 98104
Brazil
IONIS Investigative Site
Campinas, Brazil, 13059-740
IONIS Investigative Site
Sao Paulo, Brazil, 04039-030
IONIS Investigative Site
Sao Paulo, Brazil, 05403-000
Canada, British Columbia
IONIS Investigative Site
Vancouver, British Columbia, Canada, V6Z1Y6
Canada, Quebec
IONIS Investigative Site
Chicoutimi, Quebec, Canada, G7H 5H6
IONIS Investigative Site
Sainte-Foy, Quebec, Canada, G1V 4M6
France
IONIS Investigative Site
Marseille, France, 13385
IONIS Investigative Site
Nantes, France, 44093
IONIS Investigative Site
Paris, France, 75013
Germany
IONIS Investigative Site
Berlin, Germany, 13353
IONIS Investigative Site
Dresden, Germany, 01307
Hungary
IONIS Investigative Site
Szikszo, Hungary, 3800
Israel
IONIS Investigative Site
Safed, Israel, 13110
Italy
IONIS Investigative Site
Milan, Italy, 20162
IONIS Investigative Site
Palermo, Italy, 90127
IONIS Investigative Site
Rome, Italy, 00161
Netherlands
IONIS Investigative Site
Amsterdam, Netherlands, 1105 AZ
IONIS Investigative Site
Rotterdam, Netherlands, 3000
South Africa
IONIS Investigative Site
Cape Town, South Africa, 7925
Spain
IONIS Investigative Site
Zaragoza, Aragon, Spain, 50009
IONIS Investigative Site
La Coruna, Galicia, Spain, 15001
IONIS Investigative Site
Barcelona, Spain, 08036
IONIS Investigative Site
Madrid, Spain, 28007
IONIS Investigative Site
Malaga, Spain, 29010
IONIS Investigative Site
Sevilla, Spain, 41013
United Kingdom
IONIS Investigative Site
Birmingham, United Kingdom, B9 5SS
IONIS Investigative Site
Manchester, United Kingdom, M13 9WL
IONIS Investigative Site
Manchester, United Kingdom, M23 9LT
IONIS Investigative Site
Peterborough, United Kingdom, PE3 9GZ

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

Akcea Therapeutics

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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Responsible Party:	Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT02211209
Other Study ID Numbers:	ISIS 304801-CS6 2014-002421-35 ( EudraCT Number )
First Posted:	August 7, 2014 Key Record Dates
Results First Posted:	April 13, 2022
Last Update Posted:	April 13, 2022
Last Verified:	March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Hyperlipoproteinemia Type I Syndrome Disease Pathologic Processes Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors	Genetic Diseases, Inborn Hyperlipoproteinemias Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases

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