An Open-Label Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)

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

25 Feb 2022 → ongoing

Decision date (initial)

2023-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals Inc.

External identifiers

EU CT number

2023-508815-22-00

EudraCT number

2021-003635-29

WHO UTN

U1111-1298-3302

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

1. To evaluate the safety of ISIS 678354 in patients with FCS previously treated with volanesorsen
2. To evaluate the tolerability of ISIS 678354 in patients with FCS previously treated with volanesorsen

Secondary objectives 2

1. 1. To evaluate the PK effects of ISIS 678354 in patients with FCS previously treated with volanesorsen
2. 2. To evaluate the PD effects of ISIS 678354 in patients with FCS previously treated with volanesorsen

Conditions and MedDRA coding

Familial Chylomicronemia Syndrome

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. Patients with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801) Study participants in countries where Waylivra is commercially approved and available for patients should not be deprived of the treatment option with Waylivra. Participation in this study for such patients will only be allowed when Waylivra was discontinued due to AEs
2. Other protocol-defined inclusion criteria apply.

Exclusion criteria 1

1. Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer. Have any other conditions including significant medical history which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the Study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Safety endpoints include a proportion of patients who show the following changes from Baseline to Week 53, Week 105, Week 157 and Week 209 :-Decrease in platelet (PLT) count by>30% -Decrease in PLT count by>50% - PLT count value<50,000mm3 -Major bleeding events -Clinically relevant non-major bleeding events -Decrease in eGFR by>30% -Decrease in eGFR by>50% - UPCR≥1000mg/g -UACR≥500mg/g- ALT or AST>5×ULN- Total bilirubin>2.0mg/dL- ALT or AST>3×ULN and total bilirubin≥2xULN
2. 2. Tolerability assessments will include adverse events (AEs), clinical laboratory test, and use of concomitant medications

Secondary endpoints 2

1. 1. PK assessments include determination of trough (pre-dose) and post-treatment plasma ISIS 678354 concentrations
2. 2. PD endpoints include: 1. Change and percent change from Baseline to Week 53, Week 105, Week 157 and Week 209 in fasting: - Triglycerides (TG) - APOC-III, very low-density lipoprotein (VLDL)-C, chylomicron-TG, total cholesterol (TC), non-HDL-C, low-density lipoprotein (LDL)-C, apoB, apoB48, HDL-C, ApoA-1 2. Event rate of acute pancreatitis (Week 1 through Weeks: 53, 105, and 157)

Investigational products

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

Test 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 8

Locations

1 EU/EEA country · 1 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 9 files

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

Application history

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