The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome

NCT02211209 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ISIS 304801-CS62014-002421-35
• Study Type: interventional
• Target: 67
• Locations: 12 countries
• Sites: 40

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in participants with Familial Chylomicronemia Syndrome

Conditions

Familial Chylomicronemia Syndrome

Outcome Measures

Primary Outcomes (1)

• Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3

  The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.

  Baseline to 3 months

Secondary Outcomes (7)

• Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)

  Baseline to an on-treatment assessment between Week 13 and Week 19

• Absolute Change From Baseline in Fasting TG at Month 3

  Baseline to 3 months

• Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3

  Baseline to 3 months

• Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3

  Baseline to 3 months

• Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period

  Baseline to 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.

Drug: Placebo

Volanesorsen

EXPERIMENTAL

Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.

Drug: Volanesorsen

Interventions

Volanesorsen DRUG

Also known as: ISIS 304801, ApoC-III, Approach, IONIS-APOCIIIRx

Volanesorsen

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of chylomicronemia
• A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia)
• Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening

You may not qualify if:

• Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%
• Other types of severe hypertriglyceridemia
• 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
• Previous treatment with IONIS-APOCIIIRx
• Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead
• Akcea Therapeutics: collaborator

Study Sites (40)

IONIS Investigative Site

Encinitas, California, 92024, United States

Location

IONIS Investigative Site

San Francisco, California, 94143, United States

Location

IONIS Investigative Site

Kansas City, Kansas, 66214, United States

Location

IONIS Investigative Site

Boston, Massachusetts, 02114, United States

Location

IONIS Investigative Site

New York, New York, 10016, United States

Location

IONIS Investigative Site

Oklahoma City, Oklahoma, 73103, United States

Location

IONIS Investigative Site

Portland, Oregon, 97239, United States

Location

IONIS Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

IONIS Investigative Site

Houston, Texas, 77030, United States

Location

IONIS Investigative Site

Norfolk, Virginia, 23510, United States

Location

IONIS Investigative Site

Seattle, Washington, 98104, United States

Location

IONIS Investigative Site

Campinas, 13059-740, Brazil

Location

IONIS Investigative Site

São Paulo, 04039-030, Brazil

Location

IONIS Investigative Site

São Paulo, 05403-000, Brazil

Location

IONIS Investigative Site

Vancouver, British Columbia, V6Z1Y6, Canada

Location

IONIS Investigative Site

Chicoutimi, Quebec, G7H 5H6, Canada

Location

IONIS Investigative Site

Sainte-Foy, Quebec, G1V 4M6, Canada

Location

IONIS Investigative Site

Marseille, 13385, France

Location

IONIS Investigative Site

Nantes, 44093, France

Location

IONIS Investigative Site

Paris, 75013, France

Location

IONIS Investigative Site

Berlin, 13353, Germany

Location

IONIS Investigative Site

Dresden, 01307, Germany

Location

IONIS Investigative Site

Szikszó, 3800, Hungary

Location

IONIS Investigative Site

Safed, 13110, Israel

Location

IONIS Investigative Site

Milan, 20162, Italy

Location

IONIS Investigative Site

Palermo, 90127, Italy

Location

IONIS Investigative Site

Rome, 00161, Italy

Location

IONIS Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

IONIS Investigative Site

Rotterdam, 3000, Netherlands

Location

IONIS Investigative Site

Cape Town, 7925, South Africa

Location

IONIS Investigative Site

Zaragoza, Aragon, 50009, Spain

Location

IONIS Investigative Site

A Coruña, Galicia, 15001, Spain

Location

IONIS Investigative Site

Barcelona, 08036, Spain

Location

IONIS Investigative Site

Madrid, 28007, Spain

Location

IONIS Investigative Site

Málaga, 29010, Spain

Location

IONIS Investigative Site

Seville, 41013, Spain

Location

IONIS Investigative Site

Birmingham, B9 5SS, United Kingdom

Location

IONIS Investigative Site

Manchester, M13 9WL, United Kingdom

Location

IONIS Investigative Site

Manchester, M23 9LT, United Kingdom

Location

IONIS Investigative Site

Peterborough, PE3 9GZ, United Kingdom

Location

Related Publications (4)

• Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944.

  PMID: 31390500 RESULT

• Prohaska TA, Alexander VJ, Karwatowska-Prokopczuk E, Tami J, Xia S, Witztum JL, Tsimikas S. APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. J Clin Lipidol. 2023 May-Jun;17(3):406-411. doi: 10.1016/j.jacl.2023.04.007. Epub 2023 Apr 27.

  PMID: 37164837 DERIVED

• Hegele RA, Berberich AJ, Ban MR, Wang J, Digenio A, Alexander VJ, D'Erasmo L, Arca M, Jones A, Bruckert E, Stroes ES, Bergeron J, Civeira F, Witztum JL, Gaudet D. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018 Jul-Aug;12(4):920-927.e4. doi: 10.1016/j.jacl.2018.03.093. Epub 2018 Apr 4.

  PMID: 29748148 DERIVED

• Digenio A, Dunbar RL, Alexander VJ, Hompesch M, Morrow L, Lee RG, Graham MJ, Hughes SG, Yu R, Singleton W, Baker BF, Bhanot S, Crooke RM. Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes. Diabetes Care. 2016 Aug;39(8):1408-15. doi: 10.2337/dc16-0126. Epub 2016 Jun 6.

  PMID: 27271183 DERIVED

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome

Interventions

ISIS 304801; Apolipoprotein C-III

Intervention Hierarchy (Ancestors)

Apolipoproteins C; Apolipoproteins; Lipoproteins; Lipids; Apoproteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

patients@ionisph.com

800-679-4747

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 7, 2014
• Study Start: December 1, 2014
• Primary Completion: December 19, 2016
• Study Completion: March 28, 2017
• Last Updated: April 13, 2022
• Results First Posted: April 13, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); IL (1); GB (4); CA (3); NL (2); FR (3); HU (1); IT (3); DE (2); BR (3); ZA (1); ES (6)