The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
ISIS 304801-CS7 The APPROACH Open Label Study Volanesorsen (ISIS 304801) An Open-Label Study of Volanesorsen Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
2 other identifiers
interventional
68
11 countries
34
Brief Summary
An open-label study of volanesorsen (ISIS 304801) administered subcutaneously to participants with FCS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Dec 2015
Typical duration for phase_3
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 23, 2015
CompletedFirst Submitted
Initial submission to the registry
January 12, 2016
CompletedFirst Posted
Study publicly available on registry
January 18, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 15, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 15, 2020
CompletedResults Posted
Study results publicly available
August 26, 2021
CompletedAugust 26, 2021
August 1, 2021
4.1 years
January 12, 2016
August 3, 2021
August 3, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Mean Percent Change From Baseline in Fasting Triglyceride (TG)
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) and Week 26 (Day 176) fasting assessments. The values at the Month 12 analysis time point were defined as the average of the Week 50 (Day 344) and Week 52 (Day 358) fasting assessments.
Baseline and Months 3, 6, and 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
From first dose of study drug to end of follow-up period [Up to Week 182]
Study Arms (3)
Treatment-naïve Group
EXPERIMENTALTreatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6 \[NCT02211209\] and ISIS 304801-CS16 \[NCT02300233\]), were to receive 300 mg of volanesorsen as single SC once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following Week 52 visit, participants had option of participating in expanded access program or continuing treatment with 300 mg of volanesorsen as single SC once-weekly for up to additional 52 weeks (Weeks 53-104) and in France participants, up to additional 104 weeks for total of 156 weeks (Weeks 105 to Week 156) until expanded access program was approved and available in their country. Participants who were not participating in expanded access program were to enter 13-week post-treatment (PT) evaluation period and in France, participants not continuing treatment were to enter 26-week PT follow-up period.
CS6-Volanesorsen
EXPERIMENTALParticipants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
CS16-Volanesorsen
EXPERIMENTALParticipants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Interventions
300 mg volanesorsen administered via SC injection.
Eligibility Criteria
You may qualify if:
- Must give written informed consent to participate in the study (signed and dated) and any authorization required by law.
- Able and willing to participate in a 65-week study.
- Group 1 and 2:
- Satisfactory completion of ISIS 304801-CS6 (NCT02211209) or ISIS 304801-CS16 (NCT02300233) index studies with an acceptable safety profile, per Sponsor and Investigator judgment.
- Group 3:
- History of chylomicronemia.
- A diagnosis of FCS (Type 1 Hyperlipoproteinemia.)
- Fasting triglycerides greater than or equal to (≥)750 milligrams per deciliter \[mg/dL\] (8.4 millimoles per liter \[mmol/L\]) at Screening.
You may not qualify if:
- Unwilling to comply with lifestyle requirements for the duration of the study.
- Group 1 and 2:
- Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study.
- Group 3:
- Diabetes mellitus if newly diagnosed or if hemoglobin A1c (HbA1c)≥ 9.0%.
- 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.
- Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Akcea Therapeuticslead
- Ionis Pharmaceuticals, Inc.collaborator
Study Sites (34)
IONIS Investigative Site
Huntington Beach, California, 94143, United States
IONIS Investigative Site
San Francisco, California, 94143, United States
IONIS Investigative Site
Boca Raton, Florida, 33434, United States
IONIS Investigative Site
Boston, Massachusetts, 02114, United States
IONIS Investigative Site
Philadelphia, Pennsylvania, 19104, United States
IONIS Investigative Site
Houston, Texas, 77030, United States
IONIS Investigative Site
Norfolk, Virginia, 23510, United States
IONIS Investigative Site
Seattle, Washington, 98104, United States
IONIS Investigative Site
São Paulo, 04040-001, Brazil
IONIS Investigative Site
São Paulo, CEP-05403-000, Brazil
IONIS Investigative Site
Vancouver, British Columbia, V6Z1Y6, Canada
IONIS Investigative Site
Chicoutimi, Quebec, G7H 7K9, Canada
IONIS Investigative Site
Montreal, Quebec, H2W 1R7, Canada
IONIS Investigative Site
Québec, G1V 4W2, Canada
IONIS Investigative Site
Paris, Cedex 13, 75013, France
IONIS Investigative Site
Marseille, 13385, France
IONIS Investigative Site
Nantes, 44800, France
IONIS Investigative Site
Berlin, 13353, Germany
IONIS Investigative Site
Cologne, 50937, Germany
IONIS Investigative Site
Safed, 13110, Israel
IONIS Investigative Site
Palermo, 90127, Italy
IONIS Investigative Site
Roma, 00161, Italy
IONIS Investigative Site
Rome, 00161, Italy
IONIS Investigative Site
Amsterdam-Zuidoost, 1105 AZ, Netherlands
IONIS Investigative Site
Cape Town, 7925, South Africa
IONIS Investigative Site
A Coruña, 15001, Spain
IONIS Investigative Site
Barcelona, 08036, Spain
IONIS Investigative Site
Madrid, 28007, Spain
IONIS Investigative Site
Seville, 41013, Spain
IONIS Investigative Site
Zaragoza, 50009, Spain
IONIS Investigative Site
Birmingham, B9 5SS, United Kingdom
IONIS Investigative Site
London, SE1 7EH, United Kingdom
IONIS Investigative Site
Manchester, M13 9WL, United Kingdom
IONIS Investigative Site
Manchester, M23 9LT, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Akcea Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 12, 2016
First Posted
January 18, 2016
Study Start
December 23, 2015
Primary Completion
January 15, 2020
Study Completion
January 15, 2020
Last Updated
August 26, 2021
Results First Posted
August 26, 2021
Record last verified: 2021-08