Long-Term DCR-PHXC Treatment for Primary Hyperoxaluria

(PHYOX3 Trial)

Recruiting at 22 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Dicerna Pharmaceuticals, Inc.

Disqualifiers: Renal transplant, Hepatic transplant, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 years

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to provide ongoing access to the treatment DCR-PHXC for patients who were part of earlier studies and their younger siblings. It will also check if the treatment is safe and effective over an extended period. The treatment is intended for people with a condition called Primary Hyperoxaluria (PH). DCR-PHXC is designed to inhibit the enzyme responsible for the final step of oxalate production.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Nedosiran safe for humans?

Nedosiran has been generally well-tolerated in clinical studies, with no significant safety concerns reported in patients with different types of primary hyperoxaluria and varying levels of kidney function. ^{1 2 3 4 5}

How is the drug DCR-PHXC unique in treating primary hyperoxaluria?

DCR-PHXC (Nedosiran) is unique because it targets the root cause of primary hyperoxaluria by inhibiting the production of oxalate, a substance that can lead to kidney stones and damage. This approach is different from other treatments that may only address symptoms or complications rather than the underlying cause. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Nedosiran for treating primary hyperoxaluria?

Nedosiran has been shown to significantly reduce oxalate levels in patients with primary hyperoxaluria type 1, including those with advanced kidney disease, by targeting an enzyme involved in oxalate production. In a compassionate use case, it reduced the need for dialysis and delayed the need for a kidney and liver transplant, indicating its potential as an effective treatment. ^{1 2 4 5 11}

Who Is on the Research Team?

Verity Rawson, MB.CHB

Principal Investigator

Dicerna, A Novo Nordisk Company

Are You a Good Fit for This Trial?

This trial is for patients with a genetic kidney condition called Primary Hyperoxaluria who completed previous DCR-PHXC studies, and their siblings under 18 with the same condition. Participants must have a certain level of kidney function and not be on dialysis or have had a kidney or liver transplant.

Inclusion Criteria

You have already finished a Dicerna Pharmaceuticals, Inc. study of DCR PHXC.

My sibling completed a Dicerna study for DCR PHXC, I'm under 18, and have confirmed PH.

For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 75 days from the last dose of study intervention

Exclusion Criteria

I have symptoms of systemic oxalosis.

I am currently receiving dialysis.

Your plasma oxalate level is higher than 30 µmol/L.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive monthly subcutaneous injections of DCR-PHXC

6 years

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Quarterly visits (in-person)

Open-label extension

Participants continue to receive DCR-PHXC to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• DCR-PHXC

Trial Overview The study provides long-term access to DCR-PHXC for those previously enrolled in early-phase trials. It aims to assess the extended safety and effectiveness of this drug in treating Primary Hyperoxaluria.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Open label, monthly subcutaneous injection

DCR-PHXC is already approved in United States for the following indications:

Approved in United States as Rivfloza for:

• Primary hyperoxaluria type 1 (PH1)

Who Is Running the Clinical Trial?

Dicerna Pharmaceuticals, Inc.

Lead Sponsor

Trials

15

Recruited

500+

Founded

2007

Headquarters

Watertown, USA

Known For

RNA Therapeutics

Top Products

GalXC, GalXC-Plus

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Lead Sponsor

Trials

19

Recruited

580+

Published Research Related to This Trial

In a 3-month study involving 1,790 patients with gout, both extended release (XR) and immediate release (IR) formulations of febuxostat significantly reduced serum urate levels to below 5.0 mg/dl compared to placebo, demonstrating their efficacy in managing gout.

Both febuxostat formulations were well tolerated across all renal function subgroups, including those with severe renal impairment, with low rates of adverse events and no significant difference in gout flare rates among treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. Saag, KG., Becker, MA., Whelton, A., et al.[2020]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Nedosiran: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Nedosiran Dramatically Reduces Serum Oxalate in Dialysis-Dependent Primary Hyperoxaluria 1: A Compassionate Use Case Report. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4). [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Exposure-Response Modeling of Nedosiran in Participants With Severe Chronic Kidney Disease. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Reduction of albuminuria by a calcium antagonist, manidipine, in rats with passive Heymann nephritis. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Nondihydropyridine Calcium Channel Blockers for the Treatment of Proteinuria: A Review of the Literature. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. [2017]