Familial Chylomicronemia SyndromePhase 3NCT02658175
The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
A Phase 3 study testing Volanesorsen in people with Familial Chylomicronemia Syndrome and Lipoprotein Lipase Deficiency, run by Akcea Therapeutics at 34 sites in 11 countries.
Trial summary
An open-label study of volanesorsen (ISIS 304801) administered subcutaneously to participants with FCS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1
- What is being tested?
- Volanesorsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 34 sitesin 11 countries
- Study dates
- 23 Dec 2015to 15 Jan 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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 locations and contacts
34 sites in 11 countries.
34 sites in 11 countries
United States8 sites
IONIS Investigative Site
Boca Raton, Florida, 33434
IONIS Investigative Site
Boston, Massachusetts, 02114
IONIS Investigative Site
Houston, Texas, 77030
IONIS Investigative Site
Huntington Beach, California, 94143
IONIS Investigative Site
Norfolk, Virginia, 23510
IONIS Investigative Site
Philadelphia, Pennsylvania, 19104
IONIS Investigative Site
San Francisco, California, 94143
IONIS Investigative Site
Seattle, Washington, 98104
Spain5 sites
IONIS Investigative Site
A Coruña, 15001
IONIS Investigative Site
Barcelona, 08036
IONIS Investigative Site
Madrid, 28007
IONIS Investigative Site
Seville, 41013
IONIS Investigative Site
Zaragoza, 50009
Canada4 sites
IONIS Investigative Site
Chicoutimi, Quebec, G7H 7K9
IONIS Investigative Site
Montreal, Quebec, H2W 1R7
IONIS Investigative Site
Québec, G1V 4W2
IONIS Investigative Site
Vancouver, British Columbia, V6Z1Y6
United Kingdom4 sites
IONIS Investigative Site
Birmingham, B9 5SS
IONIS Investigative Site
London, SE1 7EH
IONIS Investigative Site
Manchester, M13 9WL
IONIS Investigative Site
Manchester, M23 9LT
France3 sites
IONIS Investigative Site
Marseille, 13385
IONIS Investigative Site
Nantes, 44800
IONIS Investigative Site
Paris, Cedex 13, 75013
Italy3 sites
IONIS Investigative Site
Palermo, 90127
IONIS Investigative Site
Roma, 00161
IONIS Investigative Site
Rome, 00161
Brazil2 sites
IONIS Investigative Site
São Paulo, 04040-001
IONIS Investigative Site
São Paulo, CEP-05403-000
Germany2 sites
IONIS Investigative Site
Berlin, 13353
IONIS Investigative Site
Cologne, 50937
About this study
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)
An open-label study of volanesorsen (ISIS 304801) administered subcutaneously to participants with FCS.
Read the 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.
- Conditions
- Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1
- Being tested
- Volanesorsen
- Medical subject headings
- Familial hyperchylomicronemia syndrome, Hyperlipoproteinemia Type I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolanesorsenDrug
Also called IONIS-APOCIIIRx, ISIS 304801
300 mg volanesorsen administered via SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Treatment-naïve Group | Experimental | 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. Receives: Drug: Volanesorsen |
| CS6-Volanesorsen | Experimental | 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. Receives: Drug: Volanesorsen |
| CS16-Volanesorsen | Experimental | 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. Receives: Drug: Volanesorsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Months 3, 6, and 12
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.
Measured: From first dose of study drug to end of follow-up period [Up to Week 182]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2016 (estimated)
- Study start23 Dec 2015
- Primary completion15 Jan 2020
- Study completion15 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Familial Chylomicronemia SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akcea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02658175
- Sponsor's protocol ID
- ISIS 304801-CS7
- Other IDs
- 2015-003755-21, 2015
- Status last verified
- Aug 2021
- First submitted
- 12 Jan 2016
- Last updated
- 26 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02658175
- Acronym / sponsor ID
- ISIS 304801-CS7
- Conditions
- Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Akcea TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- 23 Dec 2015 (actual)
- Primary completion
- 15 Jan 2020 (actual)
- Study completion
- 15 Jan 2020 (actual)
- First posted
- 18 Jan 2016 (estimated)
- Results
- Posted 26 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment-naïve Group | Experimental | Drug: VolanesorsenTreatment 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. |
| CS6-Volanesorsen | Experimental | Drug: VolanesorsenParticipants 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. |
| CS16-Volanesorsen | Experimental | Drug: VolanesorsenParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- Satisfactory completion of ISIS 304801-CS6 (NCT02211209) or ISIS 304801-CS16 (NCT02300233) index studies with an acceptable safety profile, per Sponsor and Investigator judgment.
- 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.
Key exclusion criteria (10 listed)
- Unwilling to comply with lifestyle requirements for the duration of the study.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VolanesorsenAlso: IONIS-APOCIIIRx, ISIS 304801300 mg volanesorsen administered via SC injection. | Drug | CS16-Volanesorsen, CS6-Volanesorsen, Treatment-naïve Group |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
34 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Volanesorsen in people with Familial Chylomicronemia Syndrome and Lipoprotein Lipase Deficiency, run by Akcea Therapeutics at 34 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, Spain, Canada, United Kingdom, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Percent Change From Baseline in Fasting Triglyceride (TG) (time frame: Baseline and Months 3, 6, and 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2021.