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

Primary Purpose

Familial Chylomicronemia Syndrome

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Volanesorsen
Placebo
Sponsored by
Ionis Pharmaceuticals, Inc.
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:

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

Exclusion Criteria:

  • 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

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
  • 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 Type

Placebo Comparator

Experimental

Arm Label

Placebo

Volanesorsen

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)
Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.
Absolute Change From Baseline in Fasting TG at Month 3
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter
Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period
Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.
Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period
Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.
Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52
The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.

Full Information

First Posted
August 5, 2014
Last Updated
March 17, 2022
Sponsor
Ionis Pharmaceuticals, Inc.
Collaborators
Akcea Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02211209
Brief Title
The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
December 2014 (Actual)
Primary Completion Date
December 19, 2016 (Actual)
Study Completion Date
March 28, 2017 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Chylomicronemia Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Volanesorsen-matching placebo administered subcutaneously once-weekly for 52 weeks.
Arm Title
Volanesorsen
Arm Type
Experimental
Arm Description
Volanesorsen 300 mg administered subcutaneously once-weekly for 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Volanesorsen
Other Intervention Name(s)
ISIS 304801, ApoC-III, Approach, IONIS-APOCIIIRx
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percent Change in Fasting Triglycerides (TG) From Baseline to Month 3
Description
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Time Frame
Baseline to 3 months
Secondary Outcome Measure Information:
Title
Change From Baseline in Postprandial TG Area Under the Curve (AUC)(0-9h)
Description
Participants had 2 postprandial assessments - one at Baseline (completed at least 48 hours prior to first dose) and one at any time between Week 13 and 19, inclusive. Assessment timepoints include from 1-hr before to up to 9 hrs after ingestion of the meal at 1-hour interval. Postprandial AUC results were calculated using a linear trapezoidal rule for each postprandial measure in the subset of participants who had postprandial assessments 0-9 hour results at baseline and the postbaseline between Week 13 to 19.
Time Frame
Baseline to an on-treatment assessment between Week 13 and Week 19
Title
Absolute Change From Baseline in Fasting TG at Month 3
Description
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Time Frame
Baseline to 3 months
Title
Treatment Response Rate Defined as Participants With Fasting Plasma TG < 750 mg/dL at Month 3
Description
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. mg/dL = milligrams per deciliter
Time Frame
Baseline to 3 months
Title
Treatment Response Rate Defined as Participants With Fasting TG ≥ 40% Reduction From Baseline at Month 3
Description
The Month 3 endpoint was defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments.
Time Frame
Baseline to 3 months
Title
Frequency and Severity of Participant-reported Abdominal Pain During the Treatment Period
Description
Abdominal pain was measured according to the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25. Missing data were imputed by using next observation carried back (NOCB) if there was a subsequent score available.
Time Frame
Baseline to 12 months
Title
Frequency of the Composite of Episodes of Acute Pancreatitis and Participant-reported Moderate/Severe Abdominal Pain During the Treatment Period
Description
Moderate/severe abdominal pain was defined as having a pain score of 4-10 on the Bracket electronic patient-reported outcomes (ePRO) assessment. Scores were categorized as follows: no pain (pain score: 0), mild (pain score: 1-3), moderate (pain score: 4-6), or severe (pain score: 7-10). The yearly frequency was calculated as the number of episodes during the on-treatment period / (last dose date - first dose date + 28) * 365.25.
Time Frame
12 months
Title
Change From Baseline in Hepatosplenomegaly as Assessed by MRI at Week 52
Description
The Week 52 endpoint was defined as the average of Week 50 (Day 344)/Week 51 (Day 351) and Week 52 (Day 358) fasting assessments.
Time Frame
Baseline to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: History of chylomicronemia A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia) Fasting triglycerides (TG) ≥ 750 mg/dL (8.4 mmol/L) at Screening Exclusion Criteria: 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
Facility Information:
Facility Name
IONIS Investigative Site
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
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
Kansas City
State/Province
Kansas
ZIP/Postal Code
66214
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
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
IONIS Investigative Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
IONIS Investigative Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
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
Campinas
ZIP/Postal Code
13059-740
Country
Brazil
Facility Name
IONIS Investigative Site
City
Sao Paulo
ZIP/Postal Code
04039-030
Country
Brazil
Facility Name
IONIS Investigative Site
City
Sao Paulo
ZIP/Postal Code
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 5H6
Country
Canada
Facility Name
IONIS Investigative Site
City
Sainte-Foy
State/Province
Quebec
ZIP/Postal Code
G1V 4M6
Country
Canada
Facility Name
IONIS Investigative Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
IONIS Investigative Site
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
IONIS Investigative Site
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
IONIS Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
IONIS Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
IONIS Investigative Site
City
Szikszo
ZIP/Postal Code
3800
Country
Hungary
Facility Name
IONIS Investigative Site
City
Safed
ZIP/Postal Code
13110
Country
Israel
Facility Name
IONIS Investigative Site
City
Milan
ZIP/Postal Code
20162
Country
Italy
Facility Name
IONIS Investigative Site
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Facility Name
IONIS Investigative Site
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
IONIS Investigative Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
IONIS Investigative Site
City
Rotterdam
ZIP/Postal Code
3000
Country
Netherlands
Facility Name
IONIS Investigative Site
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
IONIS Investigative Site
City
Zaragoza
State/Province
Aragon
ZIP/Postal Code
50009
Country
Spain
Facility Name
IONIS Investigative Site
City
La Coruna
State/Province
Galicia
ZIP/Postal Code
15001
Country
Spain
Facility Name
IONIS Investigative Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
IONIS Investigative Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
IONIS Investigative Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
IONIS Investigative Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
IONIS Investigative Site
City
Birmingham
ZIP/Postal Code
B9 5SS
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
Facility Name
IONIS Investigative Site
City
Peterborough
ZIP/Postal Code
PE3 9GZ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31390500
Citation
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.
Results Reference
result
PubMed Identifier
29748148
Citation
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.
Results Reference
derived
PubMed Identifier
27271183
Citation
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.
Results Reference
derived

Learn more about this trial

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

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