What side effects are associated with this type of intervention?

Common treatments for Primary Hyperoxaluria aimed at reducing oxalate production, such as pyridoxine and RNA interference therapies like lumasiran, have known side effects. Pyridoxine can cause peripheral neuropathy at high doses, while lumasiran may lead to injection site reactions, abdominal pain, and headache. Patients undergoing dialysis may also experience hypotension, muscle cramps, and infections.

What prior FDA approvals exist?

As of now, the FDA has approved lumasiran (Oxlumo) for the treatment of Primary Hyperoxaluria type 1 (PH1). Lumasiran works by reducing the production of oxalate, which is similar to the mechanism being studied in the DCR-PHXC trial. This RNA interference (RNAi) therapeutic targets the HAO1 gene, which encodes glycolate oxidase, thereby decreasing the production of oxalate and preventing the formation of kidney stones and other complications associated with PH1.

What other types of research exist?

Promising novel alternatives to DCR-PHXC for Primary Hyperoxaluria patients include RNA interference therapies such as lumasiran, which targets glycolate oxidase to reduce oxalate production. Additionally, gene editing approaches like CRISPR/Cas9 are being explored to correct genetic mutations responsible for PH. Other potential treatments include enzyme replacement therapies and small molecule inhibitors that target key enzymes in the oxalate production pathway.

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RNAi Therapeutics

DCR-PHXC for Kidney Failure (PHYOX7 Trial)

Phase 2

Recruiting

Research Sponsored by Dicerna Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Estimated GFR at Screening <30mL/min normalized to 1.73m^2 BSA

Documented diagnosis of PH1 or PH2, confirmed by genotyping

Must not have

Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender

Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Prior renal transplantation is allowed

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 180 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new medication called DCR-PHXC for people with severe kidney disease (PH1 or PH2). The treatment aims to protect the kidneys and improve their function. Participants will receive the medication over a period of time, with an option for continued monitoring.

Who is the study for?

This trial is for individuals with Primary Hyperoxaluria (PH1 or PH2) and severe kidney impairment, who may or may not be on dialysis. Participants must have a certain body weight, provide consent, have health insurance if required by law, and meet specific genetic diagnosis and plasma oxalate levels. There are age-specific groups from newborns to adults. Those on dialysis should have been stable for at least 2 weeks.

What is being tested?

The study tests DCR-PHXC in patients with PH1/2 who also suffer from end-stage renal disease (ESRD). It aims to assess the safety and effectiveness of this intervention in improving their condition regardless of whether they're undergoing dialysis treatment.

What are the potential side effects?

Potential side effects include reactions related to oligonucleotide-based therapies which could involve immune responses like inflammation or sensitivity issues due to ingredients in DCR-PHXC. Specific side effect profiles will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is severely reduced.

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My diagnosis of PH1 or PH2 is confirmed by genetic testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver tests are higher than normal for my age and gender.

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I have had a liver transplant or will have one soon. Kidney transplants are okay.

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

Safety: Incidence of Events

Secondary study objectives

Change from Baseline in Plasma Oxalate Concentration

Change in Duration of Dialysis

Change in Frequency of Dialysis

+5 more

Other study objectives

Change from Baseline in the EQ-5D-5L™ in adults

Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children

Change from Baseline in the Short Form (36) Health Survey (SF-36®) in adults

+2 more

Side effects data

From 2021 Phase 2 trial • 35 Patients • NCT03847909

22%

Injection site erythema

17%

Nausea

17%

Headache

Dysmenorrhoea

Neutrophil count decreased

Injection site pain

Oropharyngeal pain

Nephrolithiasis

Pain in extremity

Abdominal pain

Tachycardia

Fatigue

Blood creatine phosphokinase increased

Arthralgia

Neck pain

Renal colic

Upper respiratory tract infection

100%

80%

60%

40%

20%

Study treatment Arm

DCR-PHXC

Placebo

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DCR-PHXC

2019

Completed Phase 2

~90

0 / 4Eligibility criteria met

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 primarily aim to reduce oxalate production or mitigate its harmful effects. Glycolate oxidase inhibitors, such as CCPST, decrease oxalate production by inhibiting the enzyme that converts glycolate to glyoxylate, a precursor of oxalate. Antioxidants like N-acetylcysteine (NAC) and quercetin help reduce oxidative stress and renal damage caused by high oxalate levels. The DCR-PHXC trial focuses on substrate reduction therapy, targeting metabolic pathways to lower oxalate production. This approach is vital for PH patients as it addresses the disease's root cause, potentially reducing kidney stone formation and preserving renal function.

Protective Effects of Quercetin on Oxidative Stress-Induced Tubular Epithelial Damage in the Experimental Rat Hyperoxaluria Model.Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I.Renal cell adaptation to oxalate.