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

Primary Purpose

Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Volanesorsen
Sponsored by
Akcea Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Chylomicronemia Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site
  • IONIS Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Treatment-naïve Group

CS6-Volanesorsen

CS16-Volanesorsen

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
January 12, 2016
Last Updated
August 3, 2021
Sponsor
Akcea Therapeutics
Collaborators
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02658175
Brief Title
The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
December 23, 2015 (Actual)
Primary Completion Date
January 15, 2020 (Actual)
Study Completion Date
January 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akcea Therapeutics
Collaborators
Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment-naïve Group
Arm Type
Experimental
Arm Description
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.
Arm Title
CS6-Volanesorsen
Arm Type
Experimental
Arm Description
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.
Arm Title
CS16-Volanesorsen
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Volanesorsen
Other Intervention Name(s)
IONIS-APOCIIIRx, ISIS 304801
Intervention Description
300 mg volanesorsen administered via SC injection.
Primary Outcome Measure Information:
Title
Mean Percent Change From Baseline in Fasting Triglyceride (TG)
Description
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.
Time Frame
Baseline and Months 3, 6, and 12
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From first dose of study drug to end of follow-up period [Up to Week 182]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
IONIS Investigative Site
City
Huntington Beach
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
IONIS Investigative Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
IONIS Investigative Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33434
Country
United States
Facility Name
IONIS Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
IONIS Investigative Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
IONIS Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
IONIS Investigative Site
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
IONIS Investigative Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
IONIS Investigative Site
City
Sao Paulo
ZIP/Postal Code
04040-001
Country
Brazil
Facility Name
IONIS Investigative Site
City
Sao Paulo
ZIP/Postal Code
CEP-05403-000
Country
Brazil
Facility Name
IONIS Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z1Y6
Country
Canada
Facility Name
IONIS Investigative Site
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
IONIS Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
Facility Name
IONIS Investigative Site
City
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
IONIS Investigative Site
City
Paris
State/Province
Cedex 13
ZIP/Postal Code
75013
Country
France
Facility Name
IONIS Investigative Site
City
Marseille Cedex 05
ZIP/Postal Code
13385
Country
France
Facility Name
IONIS Investigative Site
City
Nantes cedex 1
ZIP/Postal Code
44800
Country
France
Facility Name
IONIS Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
IONIS Investigative Site
City
Cologne
ZIP/Postal Code
50937
Country
Germany
Facility Name
IONIS Investigative Site
City
Safed
ZIP/Postal Code
13110
Country
Israel
Facility Name
IONIS Investigative Site
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Facility Name
IONIS Investigative Site
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
IONIS Investigative Site
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
IONIS Investigative Site
City
Amsterdam-Zuidoost
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
IONIS Investigative Site
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
IONIS Investigative Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
IONIS Investigative Site
City
La Coruna
ZIP/Postal Code
15001
Country
Spain
Facility Name
IONIS Investigative Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
IONIS Investigative Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
IONIS Investigative Site
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
IONIS Investigative Site
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
IONIS Investigative Site
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
IONIS Investigative Site
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
IONIS Investigative Site
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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