Familial Chylomicronemia SyndromePhase 3NCT02211209
The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
A Phase 3 study testing Volanesorsen in people with Familial Chylomicronemia Syndrome, run by Ionis Pharmaceuticals, Inc. at 40 sites in 12 countries.
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Chylomicronemia Syndrome
- What is being tested?
- Volanesorsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 40 sitesin 12 countries
- Study dates
- Dec 2014to 28 Mar 2017
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of chylomicronemia
- A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia)
- Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening
Who cannot join
- 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
Trial locations and contacts
40 sites in 12 countries.
40 sites in 12 countries
United States11 sites
IONIS Investigative Site
Boston, Massachusetts, 02114
IONIS Investigative Site
Encinitas, California, 92024
IONIS Investigative Site
Houston, Texas, 77030
IONIS Investigative Site
Kansas City, Kansas, 66214
IONIS Investigative Site
New York, New York, 10016
IONIS Investigative Site
Norfolk, Virginia, 23510
IONIS Investigative Site
Oklahoma City, Oklahoma, 73103
IONIS Investigative Site
Philadelphia, Pennsylvania, 19104
IONIS Investigative Site
Portland, Oregon, 97239
IONIS Investigative Site
San Francisco, California, 94143
IONIS Investigative Site
Seattle, Washington, 98104
Spain6 sites
IONIS Investigative Site
A Coruña, Galicia, 15001
IONIS Investigative Site
Barcelona, 08036
IONIS Investigative Site
Madrid, 28007
IONIS Investigative Site
Málaga, 29010
IONIS Investigative Site
Seville, 41013
IONIS Investigative Site
Zaragoza, Aragon, 50009
United Kingdom4 sites
IONIS Investigative Site
Birmingham, B9 5SS
IONIS Investigative Site
Manchester, M13 9WL
IONIS Investigative Site
Manchester, M23 9LT
IONIS Investigative Site
Peterborough, PE3 9GZ
Brazil3 sites
IONIS Investigative Site
Campinas, 13059-740
IONIS Investigative Site
São Paulo, 04039-030
IONIS Investigative Site
São Paulo, 05403-000
Canada3 sites
IONIS Investigative Site
Chicoutimi, Quebec, G7H 5H6
IONIS Investigative Site
Sainte-Foy, Quebec, G1V 4M6
IONIS Investigative Site
Vancouver, British Columbia, V6Z1Y6
France3 sites
IONIS Investigative Site
Marseille, 13385
IONIS Investigative Site
Nantes, 44093
IONIS Investigative Site
Paris, 75013
Italy3 sites
IONIS Investigative Site
Milan, 20162
IONIS Investigative Site
Palermo, 90127
IONIS Investigative Site
Rome, 00161
Germany2 sites
IONIS Investigative Site
Berlin, 13353
IONIS Investigative Site
Dresden, 01307
Netherlands2 sites
IONIS Investigative Site
Amsterdam, 1105 AZ
IONIS Investigative Site
Rotterdam, 3000
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in participants with Familial Chylomicronemia Syndrome
- Conditions
- Familial Chylomicronemia Syndrome
- Being tested
- Volanesorsen, Placebo
- Medical subject headings
- Familial hyperchylomicronemia syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolanesorsenDrug
Also called ISIS 304801, ApoC-III, Approach, IONIS-APOCIIIRx
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks. Receives: Drug: Placebo |
| Volanesorsen | Experimental | Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks. Receives: Drug: Volanesorsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 3 months
Secondary outcomes (7)
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.
Measured: Baseline to an on-treatment assessment between Week 13 and Week 19
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.
Measured: Baseline to 3 months
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
Measured: Baseline to 3 months
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.
Measured: Baseline to 3 months
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.
Measured: Baseline to 12 months
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.
Measured: 12 months
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.
Measured: Baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2014 (estimated)
- Study startDec 2014
- Primary completion19 Dec 2016
- Study completion28 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Familial Chylomicronemia SyndromeStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Akcea Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02211209
- Sponsor's protocol ID
- ISIS 304801-CS6
- Other IDs
- 2014-002421-35, 2014
- Status last verified
- Mar 2022
- First submitted
- 5 Aug 2014
- Last updated
- 13 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31390500Prohaska TA, Alexander VJ, Karwatowska-Prokopczuk E, Tami J, Xia S, Witztum JL, Tsimikas S. APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. J Clin Lipidol. 2023 May-Jun;17(3):406-411. doi: 10.1016/j.jacl.2023.04.007. Epub 2023 Apr 27.
PubMed 37164837Hegele 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.
PubMed 29748148Digenio 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.
PubMed 27271183