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

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Placebo
Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.
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Drug: Placebo |
Experimental: Volanesorsen
Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.
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Drug: Volanesorsen
Other Names:
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- 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.
- 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.

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

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
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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |