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

Familial Chylomicronemia Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02658175
• Other study ID #: ISIS 304801-CS7
• Secondary ID: 2015-003755-21
• Status: Completed
• Phase: Phase 3
• Start date: December 23, 2015
• Est. completion date: January 15, 2020

Study information

• Verified date: August 2021
• Source: Akcea Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 15, 2020
• Est. primary completion date: January 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Chylomicronemia Syndrome
• Hyperlipidemias
• Hyperlipoproteinemia Type 1
• Hyperlipoproteinemia Type I
• Hyperlipoproteinemias
• Lipoprotein Lipase Deficiency
• Syndrome

Intervention

Drug:
• Volanesorsen
300 mg volanesorsen administered via SC injection.

Locations

Country	Name	City	State
Brazil	IONIS Investigative Site	Sao Paulo
Brazil	IONIS Investigative Site	Sao Paulo
Canada	IONIS Investigative Site	Chicoutimi	Quebec
Canada	IONIS Investigative Site	Montreal	Quebec
Canada	IONIS Investigative Site	Quebec
Canada	IONIS Investigative Site	Vancouver	British Columbia
France	IONIS Investigative Site	Marseille Cedex 05
France	IONIS Investigative Site	Nantes cedex 1
France	IONIS Investigative Site	Paris	Cedex 13
Germany	IONIS Investigative Site	Berlin
Germany	IONIS Investigative Site	Cologne
Israel	IONIS Investigative Site	Safed
Italy	IONIS Investigative Site	Palermo
Italy	IONIS Investigative Site	Roma
Italy	IONIS Investigative Site	Rome
Netherlands	IONIS Investigative Site	Amsterdam-Zuidoost
South Africa	IONIS Investigative Site	Cape Town
Spain	IONIS Investigative Site	Barcelona
Spain	IONIS Investigative Site	La Coruna
Spain	IONIS Investigative Site	Madrid
Spain	IONIS Investigative Site	Sevilla
Spain	IONIS Investigative Site	Zaragoza
United Kingdom	IONIS Investigative Site	Birmingham
United Kingdom	IONIS Investigative Site	London
United Kingdom	IONIS Investigative Site	Manchester
United Kingdom	IONIS Investigative Site	Manchester
United States	IONIS Investigative Site	Boca Raton	Florida
United States	IONIS Investigative Site	Boston	Massachusetts
United States	IONIS Investigative Site	Houston	Texas
United States	IONIS Investigative Site	Huntington Beach	California
United States	IONIS Investigative Site	Norfolk	Virginia
United States	IONIS Investigative Site	Philadelphia	Pennsylvania
United States	IONIS Investigative Site	San Francisco	California
United States	IONIS Investigative Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Akcea Therapeutics	Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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]