A Study of Olezarsen Administered Subcutaneously 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

17 May 2023 → 13 Sep 2025

Decision date (initial)

2023-03-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals Inc.

External identifiers

EU CT number

2022-501420-20-00

WHO UTN

U1111-1284-5582

ClinicalTrials.gov

NCT05552326

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Secondary objectives 5

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

Conditions and MedDRA coding

Severe hypertryglyceridemia

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 3

1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at both the Run-in period and the Qualification Period
2. Participants 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. Participants must be willing to comply with diet and lifestyle

Exclusion criteria 4

1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
2. Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper
3. Total bilirubin > 1.5 ULN unless due to Gilbert’s syndrome
4. Estimated GFR < 30 mL/min/1.73 m^2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent Change from Baseline in Fasting TG Compared to Placebo [Time Frame: Baseline and Month 6]

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 25

Locations

15 EU/EEA countries · 82 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 382 files

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

Application history

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