Open-Label Extension study of Olezarsen in Patients with Severe Hypertriglyceridemia (SHTG)
Research type
Research Study
Full title
An Open-Label Extension Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients with Severe Hypertriglyceridemia (SHTG)
IRAS ID
1008819
Contact name
Stacy Woeppel
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2022-501999-26
Clinicaltrials.gov Identifier
Research summary
Sustained chylomicronaemia can be categorised as occurring in a pure genetic form (termed Familial chylomicronaemia syndrome, FCS) or in a syndrome of mixed genetic, metabolic and environmental aetiologies termed severe hypertriglyceridemia (SHTG). Although there is overlap in the clinical disease, patients with FCS tend to have higher triglyceride (TG) levels and greater incidence of complications such as acute pancreatitis. However, the prevalence of SHTG is ~100 times more common than FCS. Patients with sustained chylomicronaemia have numerous medical and cognitive complications, but the frequent occurrence of acute and recurrent acute pancreatitis is the major cause of morbidity and even mortality. Standard therapeutic TG-lowering agents such as fibrates, fish oils and niacin as well as the use of statins and PCSK9 inhibitors may lower TG levels in varying degrees but are relatively ineffective in lowering hypertriglyceridemia associated with chylomicronaemia. In the absence of effective therapy, SHTG patients have a consistently high level of chylomicronaemia and fasting TG levels (≥ 500/dL) and are at increased risk of pancreatitis; therefore, they are a population with a major unmet medical need.
ISIS 678354-CS15 is a multi-centre, open-label extension study to confirm the safety and tolerability of olezarsen (ISIS) in the treatment of patients with severe Hypertriglyceridemia (SGHT). This study will evaluate the effect of olezarsen on reduction in fasting triglycerides (TG).
The primary endpoint is the percent change in fasting TG from baseline at Month 6 (average of Weeks 25 and 27) and the percent change in fasting TG from baseline at Month 12 (average of Weeks 51 and 53). Following qualification, approximately 700 eligible patients globally will receive 80 mg of olezarsen every 4 weeks (or 50 mg every 4 weeks if their dose was permanently reduced from 80 mg to 50 mg) in a 53-week Treatment Period.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
23/NW/0302
Date of REC Opinion
17 Nov 2023
REC opinion
Further Information Favourable Opinion