A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants with Severe Hypertriglyceridemia (SHTG)

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]

Trial duration

12 Jul 2023 → ongoing

Decision date (initial)

2024-07-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number

2022-501999-26-00

WHO UTN

U1111-1286-7078

ClinicalTrials.gov

NCT05681351

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety and tolerability of olezarsen

Secondary objectives 3

1. To evaluate the effect of treatment with olezarsen on reduction in fasting TG
2. To evaluate the effect of treatment with olezarsen on percent change from Baseline in fasting apoC-III, VLDL-C, non-HDL-C, and HDL-C
3. To evaluate the effect of treatment with olezarsen on reduction in event rate of acute pancreatitis

Conditions and MedDRA coding

Severe Hypertriglyceridemia (SHTG)

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. Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 with an acceptable safety profile, per Investigator judgment. Satisfactory completion requires that the patient did not terminate early from treatment.
2. Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. A patient may be eligible if their regimen of lipid-lowering therapy has been changed recently, provided that lipid lowering medications are optimized and stabilized for at least 4 weeks prior to the end of the Qualification Period of this OLE study; ideally, such changes are initiated after Week 53 of the index study (ISIS 678354-CS5 or -CS6).
3. A patient may re-enroll in the study after having completed the study when the Treatment Period was 53 weeks, if the patient satisfactorily completed the study with an acceptable safety profile, per Investigator judgment. For a given patient to re-enroll, there is no maximum time between their last dose of olezarsen when initially enrolled and their first dose of olezarsen when re-enrolled (i.e., not exceeding 17 weeks between doses does not apply when re-enrolling).

Exclusion criteria 1

1. Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. Although, it is acceptable to adjust a regimen of lipid-lowering therapy as described in Inclusion Criterion 3, and it is acceptable to adjust or stop lipid-lowering therapy at or after Week 13 per Investigator judgment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Proportion of Patients With Change in Laboratory Values From Baseline to Week 53, and from Baseline to Week 105, and from Baseline to Week 157. Values include platelet count value <50,000 mm^3, Clinical bleeding events, decrease in eGFR by 30%, decrease in eGFR by ≥ 50%, urine protein/creatinine ratio (UPCR) ≥1000 mg/g, urine/albumin creatinine ratio (UACR) ≥500 mg/g, ALT or AST ≥5 × upper limit of normal (ULN), total bilirubin ≥2.0 mg/dL, and ALT or AST ≥3 × ULN and total bilirubin ≥2 × ULN.
2. Proportion of Participants Who Experience Adverse Events (AEs) [Time Frame: Up to 170 weeks]
3. Proportion of Participants Who Use Concomitant Medications [Time Frame: Up to 170 weeks]

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 18

Locations

19 EU/EEA countries · 141 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 243 files

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

Application history

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