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

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ClinicalTrials.gov Identifier: NCT02658175
Recruitment Status : Completed
First Posted : January 18, 2016
Results First Posted : August 26, 2021
Last Update Posted : August 26, 2021
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Akcea Therapeutics

Study Description
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Brief Summary:
An open-label study of volanesorsen (ISIS 304801) administered subcutaneously to participants with FCS.

Condition or disease Intervention/treatment Phase
Familial Chylomicronemia Syndrome Lipoprotein Lipase Deficiency Hyperlipoproteinemia Type 1 Drug: Volanesorsen Phase 3

Detailed Description:
This is a multi-center, open-label study for FCS participants rolling over from the ISIS 304801-CS6 (NCT02211209) index study, FCS participants rolling over from the ISIS 304801-CS16 (NCT02300233) index study and Treatment-naïve group. All participants were to receive volanesorsen 300 milligrams (mg) once per week for 52 weeks. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Participants had the option of continuing dosing for an additional 52 weeks (France: up to an additional 104 weeks for a total of 156 weeks) 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 (France: 26-week) post-treatment evaluation period.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : December 23, 2015
Actual Primary Completion Date : January 15, 2020
Actual Study Completion Date : January 15, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment-naïve Group
Treatment 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.
 Drug: Volanesorsen
300 mg volanesorsen administered via SC injection.
Other Names:
  • IONIS-APOCIIIRx
  • ISIS 304801
Experimental: CS6-Volanesorsen
Participants 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.
 Drug: Volanesorsen
300 mg volanesorsen administered via SC injection.
Other Names:
  • IONIS-APOCIIIRx
  • ISIS 304801
Experimental: CS16-Volanesorsen
Participants 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.
 Drug: Volanesorsen
300 mg volanesorsen administered via SC injection.
Other Names:
  • IONIS-APOCIIIRx
  • ISIS 304801


Outcome Measures
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Primary Outcome Measures :
  1. Mean Percent Change From Baseline in Fasting Triglyceride (TG) [ Time Frame: 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) 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.

  2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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.


Eligibility Criteria
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Information from the National Library of Medicine

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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:

  • 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:

  • Participants who did not participate in the CS6 or CS16 index studies and meet additional inclusion criteria of FCS may enroll in the study.
  • 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.

Exclusion Criteria:

  • 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.
Contacts and Locations
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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): NCT02658175


Locations
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United States, California
IONIS Investigative Site
Huntington Beach, California, United States, 94143
IONIS Investigative Site
San Francisco, California, United States, 94143
United States, Florida
IONIS Investigative Site
Boca Raton, Florida, United States, 33434
United States, Massachusetts
IONIS Investigative Site
Boston, Massachusetts, United States, 02114
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
Sao Paulo, Brazil, 04040-001
IONIS Investigative Site
Sao Paulo, Brazil, CEP-05403-000
Canada, British Columbia
IONIS Investigative Site
Vancouver, British Columbia, Canada, V6Z1Y6
Canada, Quebec
IONIS Investigative Site
Chicoutimi, Quebec, Canada, G7H 7K9
IONIS Investigative Site
Montreal, Quebec, Canada, H2W 1R7
Canada
IONIS Investigative Site
Quebec, Canada, G1V 4W2
France
IONIS Investigative Site
Paris, Cedex 13, France, 75013
IONIS Investigative Site
Marseille Cedex 05, France, 13385
IONIS Investigative Site
Nantes cedex 1, France, 44800
Germany
IONIS Investigative Site
Berlin, Germany, 13353
IONIS Investigative Site
Cologne, Germany, 50937
Israel
IONIS Investigative Site
Safed, Israel, 13110
Italy
IONIS Investigative Site
Palermo, Italy, 90127
IONIS Investigative Site
Roma, Italy, 00161
IONIS Investigative Site
Rome, Italy, 00161
Netherlands
IONIS Investigative Site
Amsterdam-Zuidoost, Netherlands, 1105 AZ
South Africa
IONIS Investigative Site
Cape Town, South Africa, 7925
Spain
IONIS Investigative Site
Barcelona, Spain, 08036
IONIS Investigative Site
La Coruna, Spain, 15001
IONIS Investigative Site
Madrid, Spain, 28007
IONIS Investigative Site
Sevilla, Spain, 41013
IONIS Investigative Site
Zaragoza, Spain, 50009
United Kingdom
IONIS Investigative Site
Birmingham, United Kingdom, B9 5SS
IONIS Investigative Site
London, United Kingdom, SE1 7EH
IONIS Investigative Site
Manchester, United Kingdom, M13 9WL
IONIS Investigative Site
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Akcea Therapeutics:
Study Protocol  [PDF] May 1, 2019
Statistical Analysis Plan  [PDF] March 28, 2019

More Information
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Responsible Party: Akcea Therapeutics
ClinicalTrials.gov Identifier: NCT02658175    
Other Study ID Numbers: ISIS 304801-CS7
2015-003755-21 ( EudraCT Number )
First Posted: January 18, 2016    Key Record Dates
Results First Posted: August 26, 2021
Last Update Posted: August 26, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type I
Hyperlipoproteinemias
Hyperlipidemias
Syndrome
Disease
Pathologic Processes
 Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn