A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia.

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

8 Mar 2022 → 8 Jul 2025

Decision date (initial)

2024-06-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-510696-38-00

EudraCT number

2021-002192-19

WHO UTN

U1111-1302-3919

ClinicalTrials.gov

NCT05681351

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting TG from Baseline.

Secondary objectives 5

1. To evaluate the efficacy of olezarsen as compared to placebo on: Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L).
2. To evaluate the efficacy of olezarsen as compared to placebo on: Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L).
3. To evaluate the efficacy of olezarsen as compared to placebo on: Adjudicated acute pancreatitis event rate.
4. To evaluate the efficacy of olezarsen as compared to placebo on: Percent change from Baseline in fasting apoC-III, remnant cholesterol and non-HDL-C
5. To evaluate the efficacy of olezarsen as compared to placebo on: Absolute change in hepatic fat fraction (HFF)

Conditions and MedDRA coding

Severe Hypertriglyceridemia.

Regulatory references

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 3

1. 1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification.
2. 2. Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
3. 3. 18 Years and older (Adult, Older Adult).

Exclusion criteria 3

1. 1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening.
2. 2. Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal.
3. 3. Total bilirubin > upper limit of normal unless due to Gilbert's syndrome.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo.

Secondary endpoints 6

1. Percent Change from Baseline in Fasting TG Compared to Placebo [Time Frame: Baseline and Month 12]
2. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III), Remnant Cholesterol and Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Compared to Placebo (Time Frame: Baseline, Month 6 and 12]
3. Proportion of Patients who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo [Time Frame: Month 12]
4. Proportion of Patients Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) Compared to Placebo in the Subgroup of Patients with Baseline TG ≥ 880 mg/dL [Time Frame: Month 12]
5. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo [Time Frame: Week 1 through Week 53]
6. Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Placebo

Investigational products

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

Test 1

Placebo 1

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 21

Locations

15 EU/EEA countries · 85 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 68 files

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

Application history

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