ISIS 304801-CS17 - Broaden Study - Partial Lipodystrophy
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients with Partial Lipodystrophy
IRAS ID
184330
Contact name
Anna Stears
Contact email
Sponsor organisation
Isis Pharmaceuticals, Inc.
Eudract number
2015-000493-35
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 3 months, 27 days
Research summary
The primary objective of this study is to determine the effectiveness of ISIS 304801 in lowering triglycerides in the blood in patients with partial lipodystrophy. Partial lipodystrophy (PL) is a rare disorder in which there is loss of body fat. PL is associated with metabolic complications such as hypertriglyceridemia (high levels of a circulating fat called triglycerides) and diabetes. The study will also determine other metabolic effects, effects on body composition, and the safety of ISIS 304801 in this patient population.
Approximately 60 eligible patients worldwide will receive 300 mg of ISIS 304801 or placebo given as a subcutaneous injection once per week for 52 weeks.
ISIS 304801 is an antisense oligonucleotide drug designed to reduce Apolipoprotein CIII (apoCIII) protein production by the liver and lower triglycerides circulating in the blood. ApoCIII regulates triglyceride metabolism in the blood. People who have certain mutations in the gene for apoCIII that result in lower levels of apoCIII have lower levels of triglycerides in the blood. People with genetic changes which cause elevated levels of apoCIII have elevated triglycerides in their blood. A recent study has shown that elevated apoCIII may play a role in the hypertriglyceridemia found in patients with partial lipodystrophy. Hypertriglyceridemia is associated with multiple metabolic abnormalities, such as insulin resistance, metabolic syndrome and type 2 diabetes. People with severely elevated triglycerides are at high risk for developing acute pancreatitis.
By reducing apoCIII and triglyceride levels, ISIS 304801 may improve the metabolic profile of patients with PL and reduce their risk of acute pancreatitis. In addition, apoCIII inhibition may also improve insulin sensitivity in these patients and potentially lead to a reduction in the complications associated with diabetes. It is unknown whether this mechanism could improve hepatic steatosis and reduce cirrhosis risk.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
16/EE/0008
Date of REC Opinion
11 Mar 2016
REC opinion
Further Information Favourable Opinion