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NCT02658175

The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome

Completed Phase 3 Results posted Last updated 26 August 2021
What this trial tests

Phase 3 trial testing Volanesorsen in Familial Chylomicronemia Syndrome in 68 participants. Completed in 15 January 2020.

Timeline
23 December 2015
Primary endpoint
15 January 2020
15 January 2020

Quick facts

Lead sponsorAkcea Therapeutics
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment68
Start date23 December 2015
Primary completion15 January 2020
Estimated completion15 January 2020
Sites34 locations across France, Italy, Netherlands, South Africa, United Kingdom, Germany, Israel, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Akcea Therapeutics — full company profile →

Who can join

18 and older, any sex, with Familial Chylomicronemia Syndrome or Lipoprotein Lipase Deficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Percent Change From Baseline in Fasting Triglyceride (TG) Primary · Baseline and Months 3, 6, and 12

Baseline for treatment-naïve group was defined as the average of open-label Day 1 pre-dose assessment and the last measurement prior to open-label Day 1. Baseline for CS6-volanesorsen and CS16-volanesorsen arm groups was defined as the average of index study Day 1 pre-dose assessment and the last measurement prior index study Day 1. The values at the Month 3 analysis time point were defined as the average of the Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The Month 6 analysis time point was at the end of Month 6, and the values were defined as the average of the Week 25 (Day 169

Percent Change at Month 3
GroupValue95% CI
Treatment-naïve Group-59.8± 37.0
CS6-Volanesorsen-49.2± 34.8
CS16-Volanesorsen-64.9± 9.1
Percent Change at Month 6
GroupValue95% CI
Treatment-naïve Group-45.5± 42.9
CS6-Volanesorsen-54.8± 23.8
CS16-Volanesorsen-43.0± 19.7
Percent Change at Month 12
GroupValue95% CI
Treatment-naïve Group-36.3± 44.2
CS6-Volanesorsen-35.1± 45.6
CS16-Volanesorsen-41.6± 36.3
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · From first dose of study drug to end of follow-up period [Up to Week 182]

An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. A TEAE was defined as any AE starting or getting worse on or after the first dose of the study drug.

GroupValue95% CI
Treatment-naïve Group51
CS6-Volanesorsen14
CS16-Volanesorsen3

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug to end of follow-up period [Up to Week 182]. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment-naïve Group
Serious: 13/51 (25%)
Deaths: 0/51
CS6-Volanesorsen
Serious: 2/14 (14%)
Deaths: 0/14
CS16-Volanesorsen
Serious: 2/3 (67%)
Deaths: 0/3

Serious adverse events (17 terms)

ReactionSystemTreatment-naïve GroupCS6-VolanesorsenCS16-Volanesorsen
ThrombocytopeniaBlood and lymphatic system disorders
PancreatitisGastrointestinal disorders
Pancreatitis acuteGastrointestinal disorders
Pancreatitis chronicGastrointestinal disorders
ArthritisMusculoskeletal and connective tissue disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Tendon calcificationMusculoskeletal and connective tissue disorders
Influenza like illnessGeneral disorders
DiverticulitisInfections and infestations
Urinary tract infectionInfections and infestations
Clavicle fractureInjury, poisoning and procedural complications
Haemoglobin decreasedInvestigations
Diabetes mellitus inadequate controlMetabolism and nutrition disorders
Abortion spontaneousPregnancy, puerperium and perinatal conditions
Focal segmental glomerulosclerosisRenal and urinary disorders
Ovarian cystReproductive system and breast disorders
Other adverse events (126 terms — click to expand)

ReactionSystemTreatment-naïve GroupCS6-VolanesorsenCS16-Volanesorsen
Injection site erythemaGeneral disorders
Injection site painGeneral disorders
NasopharyngitisInfections and infestations
Platelet count decreasedInvestigations
Injection site swellingGeneral disorders
Abdominal painGastrointestinal disorders
Injection site discolourationGeneral disorders
HeadacheNervous system disorders
Injection site pruritusGeneral disorders
Injection site indurationGeneral disorders
PyrexiaGeneral disorders
NauseaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
InfluenzaInfections and infestations
Urinary tract infectionInfections and infestations
FatigueGeneral disorders
Abdominal pain upperGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
DiarrhoeaGastrointestinal disorders
Injection site bruisingGeneral disorders
Injection site haematomaGeneral disorders
Injection site oedemaGeneral disorders
BronchitisInfections and infestations
GastroenteritisInfections and infestations
Abdominal distensionGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Alanine aminotransferase increasedInvestigations
Ear infectionInfections and infestations
SinusitisInfections and infestations
DyspepsiaGastrointestinal disorders
Abdominal discomfortGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
EcchymosisSkin and subcutaneous tissue disorders

Most-reported serious reactions: Thrombocytopenia, Pancreatitis, Pancreatitis acute, Pancreatitis chronic, Arthritis, Intervertebral disc protrusion, Myalgia, Tendon calcification.

Data from ClinicalTrials.gov NCT02658175 adverse events section.

Sponsor's own description

An open-label study of volanesorsen (ISIS 304801) administered subcutaneously to participants with FCS.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention.
    Kong P, Cui ZY, Huang XF, Zhang DD, et al · · 2022 · cited 749× · PMID 35459215 · DOI 10.1038/s41392-022-00955-7
  2. Advances in the delivery of RNA therapeutics: from concept to clinical reality.
    Kaczmarek JC, Kowalski PS, Anderson DG. · · 2017 · cited 467× · PMID 28655327 · DOI 10.1186/s13073-017-0450-0
  3. Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside.
    Zatsepin TS, Kotelevtsev YV, Koteliansky V. · · 2016 · cited 124× · PMID 27462152 · DOI 10.2147/ijn.s106625
  4. Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.
    Liu M, Wang Y, Zhang Y, Hu D, et al · · 2025 · cited 62× · PMID 40059188 · DOI 10.1038/s41392-024-02112-8
  5. Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy.
    Zhang C, Ma Y, Zhang J, Kuo JC, et al · · 2022 · cited 57× · PMID 35335310 · DOI 10.3390/molecules27061943
  6. Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias.
    Gareri C, Polimeni A, Giordano S, Tammè L, et al · · 2022 · cited 36× · PMID 35807171 · DOI 10.3390/jcm11133884
  7. Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials.
    Calcaterra I, Lupoli R, Di Minno A, Di Minno MND. · · 2022 · cited 25× · PMID 35851450 · DOI 10.1111/eci.13841
  8. Current RNA strategies in treating cardiovascular diseases.
    Chia SPS, Pang JKS, Soh BS. · · 2024 · cited 13× · PMID 38291757 · DOI 10.1016/j.ymthe.2024.01.028

Verify or expand the search:

Other trials of Volanesorsen

Trials testing the same drug.

Other recruiting trials for Familial Chylomicronemia Syndrome

Currently open trials in the same condition.

Other Akcea Therapeutics trials

Trials by the same sponsor.

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