What is the mechanism of action of this treatment?

Primary Hyperoxaluria (PH) treatments focus on reducing oxalate production to prevent kidney stones and renal damage. Nedosiran, an RNA interference therapy, targets and silences the gene for glycolate oxidase, an enzyme critical in oxalate synthesis. By reducing the activity of this enzyme, nedosiran lowers oxalate levels, addressing the root cause of the disease. This is vital for PH patients as it can decrease the incidence of kidney stones and help maintain kidney function.

What side effects are associated with this type of intervention?

Common treatments for Primary Hyperoxaluria, particularly those targeting oxalate production like RNA interference therapies, may include side effects such as injection site reactions, flu-like symptoms, and potential liver enzyme elevations. Broader treatments for reducing oxalate levels can also lead to gastrointestinal disturbances, fatigue, and potential impacts on kidney function. It is essential to monitor these side effects closely under medical supervision.

What prior FDA approvals exist?

As of now, the FDA has approved lumasiran, an RNA interference (RNAi) therapeutic, for the treatment of Primary Hyperoxaluria type 1 (PH1). Lumasiran works by targeting the HAO1 mRNA, which encodes glycolate oxidase, thereby reducing oxalate production. This mechanism is similar to that of Nedosiran, which is also an RNAi therapeutic targeting glycolate oxidase to reduce oxalate levels. Other treatments for Primary Hyperoxaluria have included supportive measures such as hydration, dietary modifications, and in severe cases, organ transplantation.

What other types of research exist?

Promising novel alternatives to Nedosiran for Primary Hyperoxaluria patients include: 1) Lumasiran, an RNA interference therapy targeting hydroxyacid oxidase 1 (HAO1) to reduce oxalate production, which has shown efficacy in clinical trials. 2) Stiripentol, a drug that has been investigated for its potential to reduce oxalate levels by inhibiting lactate dehydrogenase. 3) Gene therapy approaches, which aim to correct the genetic mutations causing PH, are also under investigation and hold potential for long-term treatment solutions.

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RNAi Therapeutics

Nedosiran for Primary Hyperoxaluria (PHYOX8 Trial)

Phase 2

Recruiting

Research Sponsored by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 180 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing nedosiran, a medication, in children with a rare kidney condition called Primary Hyperoxaluria. The goal is to see if it can reduce harmful oxalate levels and protect their kidneys.

Who is the study for?

This trial is for children from birth to 11 years with Primary Hyperoxaluria (PH), a genetic disorder affecting the kidneys, who have normal or near-normal kidney function. Participants need a legal guardian to consent and help with study requirements, must not be pregnant or breastfeeding if applicable, and should be on stable PH treatment for at least 3 months.

What is being tested?

The trial is testing nedosiran, a medication intended to treat Primary Hyperoxaluria in young patients. It aims to evaluate its effectiveness and safety in those who still have relatively good kidney function.

What are the potential side effects?

While specific side effects of nedosiran are not listed here, similar drugs can cause reactions like flu-like symptoms, liver issues indicated by blood tests changes, severe skin reactions at injection sites, and potential allergic responses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 180 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~180 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 180 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Efficacy: Absolute change in urinary oxalate to creatinine ratio

Efficacy: Percent change in urinary oxalate to creatinine ratio

Secondary study objectives

Efficacy: eGFR changes

Safety: Changes from baseline in ECG: PR interval

Safety: Changes from baseline in ECG: QRS duration

+21 more

Other study objectives

Change from Baseline in Plasma Oxalate Concentration

Change from Baseline number of kidney stones

Change from baseline PedsQL™

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Open-Label DCR-PHXCExperimental Treatment1 Intervention

Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Primary Hyperoxaluria (PH) treatments focus on reducing oxalate production to prevent kidney stones and renal damage. Nedosiran, an RNA interference therapy, targets and silences the gene for glycolate oxidase, an enzyme critical in oxalate synthesis. By reducing the activity of this enzyme, nedosiran lowers oxalate levels, addressing the root cause of the disease. This is vital for PH patients as it can decrease the incidence of kidney stones and help maintain kidney function.

The role of reactive oxygen species derived from different NADPH oxidase isoforms and mitochondria in oxalate-induced oxidative stress and cell injury.In vivo oxalate degradation by liposome encapsulated oxalate oxidase in rat model of hyperoxaluria.