A phase 3 study of ISIS 678354 in patients with severe hypertriglyceridemia
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients with Severe Hypertriglyceridemia
IRAS ID
1004410
Contact name
Matt Buck
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2021-002192-19
Clinicaltrials.gov Identifier
Research summary
Sustained chylomicronaemia can be categorized 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-CS5 is a multi-center, randomized, double-blind, placebo-controlled Phase 3 study to confirm the safety and efficacy of ISIS 678354 as compared to placebo on the percent change in fasting TG from baseline for the treatment of patients with severe Hypertriglyceridemia. The primary endpoint is the percent change in fasting TG from baseline at Month 6 (average of Weeks 25 and 27) compared to placebo. Following qualification, approximately 540 eligible patients will be randomized 1:1 to Cohort A (50 mg) or Cohort B (80 mg) and within each cohort further randomized 2:1 to receive ISIS 678354 or matching placebo in a 53-week Treatment Period.
REC name
London - London Bridge Research Ethics Committee
REC reference
22/LO/0320
Date of REC Opinion
10 Jun 2022
REC opinion
Further Information Favourable Opinion