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

Akcea Therapeutics

Status and phase: Completed; Phase 3

Conditions: Hyperlipoproteinemia Type 1; Lipoprotein Lipase Deficiency; Familial Chylomicronemia Syndrome

Treatments: Drug: Volanesorsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT02658175

2015-003755-21 (EudraCT Number)

ISIS 304801-CS7

Details and patient eligibility

About

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

Full 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.

Enrollment: 68 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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68 participants in 3 patient groups

Treatment-naïve Group

Experimental group

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.

Treatment:

Drug: Volanesorsen

CS6-Volanesorsen

Experimental group

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.

Treatment:

Drug: Volanesorsen

CS16-Volanesorsen

Experimental group

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.

Treatment:

Drug: Volanesorsen