A controlled clinical trial of ISIS 304801 in patients with Familial Chylomicronemia Syndrome (FCS)

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 304801 Administered Subcutaneously to Patients with Familial Chylomicronemia Syndrome (FCS)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-002421-35-GB

Enrollment

Registered

2014-07-23

Start date

2014-10-27

Completion date

Unknown

Last updated

2017-05-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Familial Chylomicronemia Syndrome (FCS) MedDRA version: 18.1 Level: LLT Classification code 10017339 Term: Fredrickson Type I lipidaemia System Organ Class: 100000004850 MedDRA version: 18.1 Level: LLT Classification code 10060593 Term: Fredrickson Type I lipidemia System Organ Class: 100000004850

Interventions

Product Name: ApoC-III Antisense Oligonucleotide Product Code: ISIS 304801 Pharmaceutical Form: Solution for injection INN or Proposed INN: ISIS 304801 CAS Number: 915430-78-3 Current Sponsor code: IS

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • History of chylomicronemia • A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia) • Fasting triglycerides = 750 mg/dL (8.4 mmol/L) at Screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

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 or major surgery within 3 months of screening • History of heart failure • Treatment with Glybera gene therapy within 2 years of screening • Previous treatment with APOCIII Rx • Have any other conditions in the opinion of the investigator which could interfere with the patient participating in or completing the study

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the percent change in fasting TG from baseline.;Secondary Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the following: • Postprandial TG change from baseline • Absolute change from baseline in fasting TG • Proportion of patients who achieve fasting TG <750 mg/dL • Proportion of patients who achieve =40% fasting TG reduction from baseline • Patient reported abdominal pain o Frequency o Severity • Composite of episodes of acute pancreatitis and patient reported abdominal pain • Change from baseline in hepatosplenomegaly as assessed by MRI;Primary end point(s): The % change in fasting TG from baseline as measured at the primary analysis time point. ;Timepoint(s) of evaluation of this end point: The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments.	—

Measure

Time frame

Main Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the percent change in fasting TG from baseline.;Secondary Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the following: • Postprandial TG change from baseline • Absolute change from baseline in fasting TG • Proportion of patients who achieve fasting TG <750 mg/dL • Proportion of patients who achieve =40% fasting TG reduction from baseline • Patient reported abdominal pain o Frequency o Severity • Composite of episodes of acute pancreatitis and patient reported abdominal pain • Change from baseline in hepatosplenomegaly as assessed by MRI;Primary end point(s): The % change in fasting TG from baseline as measured at the primary analysis time point. ;Timepoint(s) of evaluation of this end point: The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments.

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Secondary

Measure	Time frame
Secondary end point(s): • Postprandial TG (AUC) change from baseline • Absolute change from baseline in fasting TG as measured at the primary analysis time point. • Treatment response rate, where a patient with fasting plasma TG <750 mg/dL at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. • Treatment response rate, where a patient who achieves fasting TG =40% reduction from baseline at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. • Frequency and severity of patient reported abdominal pain during the treatment period • Composite of episodes of acute pancreatitis and patient reported abdominal pain during the treatment period • Change from baseline in hepatosplenomegaly as assessed by MRI at Week 26;Timepoint(s) of evaluation of this end point: Month 3 (defined as he average of Week 12 and Week 13 fasting assessments) , Month 6 (defined as the average of Week 25 and Week 26 fasting assessments) and Month 12 (defined as the average of Week 51 and Week 52 fasting assessments)	—

Measure

Time frame

Secondary end point(s): • Postprandial TG (AUC) change from baseline • Absolute change from baseline in fasting TG as measured at the primary analysis time point. • Treatment response rate, where a patient with fasting plasma TG <750 mg/dL at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. • Treatment response rate, where a patient who achieves fasting TG =40% reduction from baseline at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. • Frequency and severity of patient reported abdominal pain during the treatment period • Composite of episodes of acute pancreatitis and patient reported abdominal pain during the treatment period • Change from baseline in hepatosplenomegaly as assessed by MRI at Week 26;Timepoint(s) of evaluation of this end point: Month 3 (defined as he average of Week 12 and Week 13 fasting assessments) , Month 6 (defined as the average of Week 25 and Week 26 fasting assessments) and Month 12 (defined as the average of Week 51 and Week 52 fasting assessments)

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Countries

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

Contacts

Public ContactTeresa Brandt

Ionis Pharmaceuticals, Inc.

tbrandt@ionish.com011760603-2738

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026