Plozasiran for High Triglycerides (MUIR-3 Trial)
Recruiting in Palo Alto (17 mi)
+211 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Arrowhead Pharmaceuticals
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with hypertriglyceridemia (HTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo and be evaluated for efficacy and safety.
Is the drug Plozasiran a promising treatment for high triglycerides?
Yes, Plozasiran is a promising drug for high triglycerides. It targets apolipoprotein C-III, which is linked to high triglyceride levels and increased risk of heart disease. By reducing apolipoprotein C-III, Plozasiran can lower triglyceride levels and potentially reduce the risk of heart-related problems.
12367What safety data exists for Plozasiran (ARO-APOC3) treatment?
The research does not provide specific safety data for Plozasiran (ARO-APOC3). However, it discusses the safety and efficacy of antisense oligonucleotides targeting apolipoprotein C-III, such as volanesorsen, which is in phase 3 trials. These treatments have shown promise in reducing triglyceride levels and managing hypertriglyceridemia, but specific safety data for Plozasiran is not mentioned.
34567What data supports the idea that Plozasiran for High Triglycerides is an effective drug?
The available research shows that targeting apolipoprotein C-III (apoC-III) is a promising approach for lowering triglyceride levels, which are linked to cardiovascular disease. Although the specific data on Plozasiran is not provided, similar drugs targeting apoC-III, like volanesorsen, have shown positive results in clinical trials. These drugs work by reducing apoC-III, which helps lower triglyceride levels and potentially reduces the risk of heart disease. Compared to traditional treatments like fibrates and omega-3 fatty acids, which sometimes fail to achieve normal triglyceride levels, apoC-III inhibitors are emerging as a more effective option.
36789Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop your current medications. However, you must be on standard lipid-lowering medications unless you are intolerant. Some specific medications, like certain siRNAs, are restricted before the trial.
Eligibility Criteria
Adults with high triglycerides who have a stable blood sugar level (HbA1c ≤8.5%), can maintain a low-fat diet, and have LDL cholesterol levels within specific limits. Participants must have documented hypertriglyceridemia with certain fasting triglyceride levels, be on standard lipid-lowering medications unless intolerant.Inclusion Criteria
My medical records show I have high triglycerides between 150 and 499 mg/dL.
My fasting triglyceride levels are between 150 and 499 mg/dL, confirmed by two tests.
Exclusion Criteria
I haven't used specific liver-targeted gene therapy recently.
Participant Groups
The trial is testing Plozasiran injections against a placebo in adults with hypertriglyceridemia to see if it's safe and effective. Participants will receive four doses over the course of a year, with each dose given every three months.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Plozasiran InjectionExperimental Treatment1 Intervention
4 doses of plozasiran by subcutaneous (sc) injection
Group II: PlaceboPlacebo Group1 Intervention
calculated volume to match active treatment by sc injection
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
National Institute of Clinical ResearchGarden Grove, CA
Innovative Research of West Florida, Inc.Clearwater, FL
Florida Institute for Clinical ResearchOrlando, FL
Annapolis Internal MedicineAnnapolis, MD
More Trial Locations
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Who is running the clinical trial?
Arrowhead PharmaceuticalsLead Sponsor
References
Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. [2022]Apolipoprotein C-III (APOC3) is a key regulator of plasma triglyceride levels. Elevated triglyceride levels are associated with a risk of adverse cardiovascular events and pancreatitis. ISIS 304801 is a second-generation antisense inhibitor of APOC3 synthesis.
Targeting ApoC-III to Reduce Coronary Disease Risk. [2018]Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III. Here, we briefly review both currently available as well as developing therapies for reducing apoC-III levels and function to lower TGs and cardiovascular risk. These therapies include existing options including statins, fibrates, thiazolidinediones, omega-3-fatty acids, and niacin, as well as an antisense oligonucleotide targeting APOC3 currently in clinical development. We review the mechanisms of action by which these drugs reduce apoC-III and the current understanding of how reduction in apoC-III may impact CAD risk.
Why Is Apolipoprotein CIII Emerging as a Novel Therapeutic Target to Reduce the Burden of Cardiovascular Disease? [2018]ApoC-III was discovered almost 50 years ago, but for many years, it did not attract much attention. However, as epidemiological and Mendelian randomization studies have associated apoC-III with low levels of triglycerides and decreased incidence of cardiovascular disease (CVD), it has emerged as a novel and potentially powerful therapeutic approach to managing dyslipidemia and CVD risk. The atherogenicity of apoC-III has been attributed to both direct lipoprotein lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in vascular cells and impairing LPL-independent hepatic clearance of TRL remnants. Encouraging results from clinical trials using antisense oligonucleotide, which selectively inhibits apoC-III, indicate that modulating apoC-III may be a potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.
APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia. [2019]Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) is associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review, we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. [2018]Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apo-CIII production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
Metabolic characterisation of disturbances in the APOC3/triglyceride-rich lipoprotein pathway through sample-based recall by genotype. [2022]High plasma triacylglyceride levels are known to be associated with increased risk of atherosclerotic cardiovascular disease. Apolipoprotein C-III (apoC-III) is a key regulator of plasma triacylglyceride levels and is associated with hypertriglyceridemia via a number of pathways. There is consistent evidence for an association of cardiovascular events with blood apoC-III level, with support from human genetic studies of APOC3 variants. As such, apoC-III has been recognised as a potential therapeutic target for patients with severe hypertriglyceridaemia with one of the most promising apoC-III-targeting drugs, volanesorsen, having recently progressed through Phase III trials.
Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. [2022]Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease.
Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia. [2022]Hypertriglyceridemia has been identified as a risk factor for cardiovascular disease and acute pancreatitis. To date, there are only few drug classes targeting triglyceride levels such as fibrates and ω-3 fatty acids. These agents are at times insufficient to address very high triglycerides and the residual cardiovascular risk in patients with mixed dyslipidemia. To address this unmet clinical need, novel triglyceride-lowering agents have been in different phases of early clinical development. In this review, the latest and experimental therapies for the management of hypertriglyceridemia are presented. Specifically, ongoing trials evaluating novel apolipoprotein C-III inhibitors, ω-3 fatty acids, as well as fibroblast growth 21 analogues are discussed.
New therapeutic approaches for the treatment of hypertriglyceridemia. [2022]Patients with hypertriglyceridemia (> 150 mg/dl) have an increased risk for atherosclerotic cardiovascular disease, and those with severe hypertriglyceridemia (> 880 mg/dl) also for pancreatitis. The currently available medications to decrease triglyceride levels, such as fibrates, statins, and omega‑3 fatty acids, are in many cases not able to achieve normal triglyceride levels. Therefore, new drugs are in development to address this unmet need. Recently, icosapent ethyl, a purified formulation of the omega-3-fatty acid eicosapentaenoic acid, was approved in Germany for the reduction of cardiovascular events in patients with hypertriglyceridemia and established cardiovascular disease or with diabetes and other risk factors on top of statins. Other new drugs in development are the more selective peroxisome proliferator-activated receptor α (PPARα) modulator, pemafibrate, already approved for the treatment of hypertriglyceridemia in Japan, and inhibitors of ApoC-III and angiopoietin-like 3 (ANGPTL3) in the form of antisense oligonucleotides or siRNAs or fully human monoclonal binding antibodies. Apolipoprotein C-III and ANGPTL3 protein seem to be quite promising targets based on solid genetic data. Larger studies of long duration, many of them currently ongoing, are needed to establish the role these medications will play in the treatment of hypertriglyceridemia in clinical practice.