An Open-Label Extension Study of AKCEA-APOCIII-LRX Administered to Patients with Familial Chylomicronemia Syndrome (FCS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ionis Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

29 Jun 2022 → ongoing

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number

2023-509029-29-00

EudraCT number

2021-003280-95

WHO UTN

U1111-1299-3265

ClinicalTrials.gov

NCT05130450

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy

To evaluate the effect of olezarsen on the percent change in fasting triglycerides (TG) from Baseline

Secondary objectives 9

1. To evaluate effect of olezarsen as compared to baseline on percent change in fasting TG upon extended treatment (durability of the effect)
2. To evaluate effect of olezarsen as compared to baseline on proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline
3. To evaluate effect of olezarsen as compared to baseline on percent change in fasting apolipoprotein C-III (apoC-III), apolipoprotein B (apoB), apolipoprotein 48 (apoB48) and non-HIgh Density Lipoprotein Cholesterol (non-HDL-C) from Baseline
4. To evaluate effect of olezarsen as compared to baseline on proportion of patients who achieve fasting TG ≤ 880 mg/dL
5. To evaluate effect of olezarsen as compared to baseline on adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105, 157 or 209)
6. To evaluate effect of olezarsen as compared to baseline on adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105, 157 or 209 in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to treatment with study drug in the index study
7. To evaluate effect of olezarsen as compared to baseline on adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105, 157 or 209) and in patients with a prior history of pancreatitis within 10 years prior to Screening in the index study
8. To evaluate effect of olezarsen as compared to baseline on proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline
9. To evaluate effect of olezarsen as compared to baseline on proportion of patients who achieve fasting TG ≤ 500 mg/dL

Conditions and MedDRA coding

Familial Chylomicronemia Syndrome (FCS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Satisfactory completion of the ISIS 678354 CS3 index study (last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement
2. Willing to follow a diet comprising ≤ 20 g fat per day during the study

Exclusion criteria 1

1. Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective is to evaluate safety and tolerability of treatment with olezarsen

Secondary endpoints 12

1. Percent change in fasting TG from Baseline at Month 6 (average of Weeks 23, 25 and 27)
2. Percent change in fasting TG from Baseline at Month 12 (average of Week 51 and 53), Month 24 (average of Week 103 and Week 105) and Month 36 (average of Week 155 and Week 157), and Month 48 (average of Week 205 and 209)
3. Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline at Month 6, 12, 24, 36, 48
4. Percent change in fasting apoB48 from Baseline at Month 6, 12, 24, 36, 48
5. Percent change in fasting apoC-III from Baseline at Month 6, 12, 24, 36, 48
6. Percent change in fasting non-HDL from Baseline at Month 6, 12, 24, 36, 48
7. Proportion of patients who achieve fasting TG 880mg/dL at Month 6, 12, 24, 36, 48
8. Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105, 157 or 209)
9. Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105 157 or 209), in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to treatment with study drug in the index study
10. Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105 157 or 209) in patient with a prior history of pancreatitis within 10 years prior to Screening in the index study
11. Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline at Month 6, 12, 24, 36, 48
12. Proportion of patients who achieve fasting TG ≤ 500 mg/dL at Month 6, 12, 24, 36, 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ionis Pharmaceuticals Inc.

Sponsor organisation

Ionis Pharmaceuticals Inc.

Address

2855 Gazelle Court

City

Carlsbad

Postcode

92010-6670

Country

United States

Scientific contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Global Regulatory Affairs

Third parties 8

Locations

7 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications