A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or 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] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

8 Jun 2023 → 31 May 2025

Decision date (initial)

2023-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number

2022-503022-13-00

WHO UTN

U1111-1285-6807

ClinicalTrials.gov

NCT05610280

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo

Secondary objectives 4

1. To evaluate the effect of olezarsen as compared to placebo on percent change in fasting TG levels upon longer duration of treatment (1 year)
2. To evaluate the effect of olezarsen as compared to placebo on proportion of patients who achieve different thresholds in fasting TG
3. To evaluate the effect of olezarsen as compared to placebo on percent change in fasting apolipoprotein C III (apoC-III), very low-density lipoprotein cholesterol (VLDL-C), remnant cholesterol, non high-density lipoprotein cholesterol (non-HDL-C), high density lipoprotein cholesterol (HDL-C), apoB, and low density lipoprotein cholesterol (LDL C).
4. To evaluate safety and tolerability of olezarsen

Conditions and MedDRA coding

Hypertriglyceridemia, Cardiovascular Diseases, Atherosclerosis

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 4

1. Participants must fall into 1 of the following groups (a or b): a. Hypertriglyceridemia with fasting TG ≥ 200 mg/dL (2.26 mmol/L) and < 500 mg/dL (5.65 mmol/L) b. Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L)
2. Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or
3. At increased risk for ASCVD
4. Participants should be on standard of care (SOC) lipid-lowering medications 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.

Exclusion criteria 4

1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
2. Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
3. Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
4. Estimated GFR < 30 mL/min/1.73 m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in fasting TG from Baseline at Week 25 compared to placebo.

Secondary endpoints 4

1. Percent change in fasting TG from Baseline at Week 53 compared to placebo
2. Proportion of patients who achieve fasting TG < 150 mg/dL (1. 69 mmol/L) at Week 25 and proportion of patients who achieve fasting TG < 150 mg/dL at Week 53 compared to placebo
3. Percent change in fasting apoC-III, VLDL-C, remnant cholesterol, non-HDL-C, HDL-C, apoB, and LDL-C from Baseline at Week 25 and at Week 53 compared to placebo
4. Safety and tolerability assessments include: adverse events (AEs), vital signs and weight, physical examinations, clinical laboratory tests, electrocardiogram (ECG), and use of concomitant medications. Safety and tolerability results in patients receiving olezarsen will be compared with those receiving 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 14

Locations

13 EU/EEA countries · 93 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 206 files

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

Application history

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