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

NCT ID: NCT02658175

Last Updated: 2021-08-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-23

Study Completion Date

2020-01-15

Brief Summary

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

Detailed Description

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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.

Conditions

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Familial Chylomicronemia Syndrome Lipoprotein Lipase Deficiency Hyperlipoproteinemia Type 1

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Volanesorsen

Intervention Type DRUG

300 mg volanesorsen administered via SC injection.

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.

Group Type EXPERIMENTAL

Volanesorsen

Intervention Type DRUG

300 mg volanesorsen administered via SC injection.

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.

Group Type EXPERIMENTAL

Volanesorsen

Intervention Type DRUG

300 mg volanesorsen administered via SC injection.

Interventions

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Volanesorsen

300 mg volanesorsen administered via SC injection.

Intervention Type DRUG

Other Intervention Names

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IONIS-APOCIIIRx ISIS 304801

Eligibility Criteria

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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:

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Akcea Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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IONIS Investigative Site

Huntington Beach, California, United States

Site Status

IONIS Investigative Site

San Francisco, California, United States

Site Status

IONIS Investigative Site

Boca Raton, Florida, United States

Site Status

IONIS Investigative Site

Boston, Massachusetts, United States

Site Status

IONIS Investigative Site

Philadelphia, Pennsylvania, United States

Site Status

IONIS Investigative Site

Houston, Texas, United States

Site Status

IONIS Investigative Site

Norfolk, Virginia, United States

Site Status

IONIS Investigative Site

Seattle, Washington, United States

Site Status

IONIS Investigative Site

São Paulo, , Brazil

Site Status

IONIS Investigative Site

São Paulo, , Brazil

Site Status

IONIS Investigative Site

Vancouver, British Columbia, Canada

Site Status

IONIS Investigative Site

Chicoutimi, Quebec, Canada

Site Status

IONIS Investigative Site

Montreal, Quebec, Canada

Site Status

IONIS Investigative Site

Québec, , Canada

Site Status

IONIS Investigative Site

Paris, Cedex 13, France

Site Status

IONIS Investigative Site

Marseille, , France

Site Status

IONIS Investigative Site

Nantes, , France

Site Status

IONIS Investigative Site

Berlin, , Germany

Site Status

IONIS Investigative Site

Cologne, , Germany

Site Status

IONIS Investigative Site

Safed, , Israel

Site Status

IONIS Investigative Site

Palermo, , Italy

Site Status

IONIS Investigative Site

Roma, , Italy

Site Status

IONIS Investigative Site

Rome, , Italy

Site Status

IONIS Investigative Site

Amsterdam-Zuidoost, , Netherlands

Site Status

IONIS Investigative Site

Cape Town, , South Africa

Site Status

IONIS Investigative Site

A Coruña, , Spain

Site Status

IONIS Investigative Site

Barcelona, , Spain

Site Status

IONIS Investigative Site

Madrid, , Spain

Site Status

IONIS Investigative Site

Seville, , Spain

Site Status

IONIS Investigative Site

Zaragoza, , Spain

Site Status

IONIS Investigative Site

Birmingham, , United Kingdom

Site Status

IONIS Investigative Site

London, , United Kingdom

Site Status

IONIS Investigative Site

Manchester, , United Kingdom

Site Status

IONIS Investigative Site

Manchester, , United Kingdom

Site Status

Countries

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United States Brazil Canada France Germany Israel Italy Netherlands South Africa Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-003755-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 304801-CS7

Identifier Type: -

Identifier Source: org_study_id

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