Long-Term DCR-PHXC Treatment for Primary Hyperoxaluria

(PHYOX3 Trial)

Not currently recruiting at 23 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial assesses the long-term safety and effectiveness of DCR-PHXC, a treatment for primary hyperoxaluria (PH), a rare condition that causes excessive oxalate buildup, potentially leading to kidney damage. Participants will receive monthly injections, and the study aims to provide long-term access to the treatment. Those who have successfully completed earlier trials with DCR-PHXC or are siblings under 18 with confirmed PH may be eligible to join. This trial may suit individuals who have participated in previous studies or have a sibling who has. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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 there any evidence suggesting that DCR-PHXC is likely to be safe for humans?

Research has shown that DCR-PHXC, also known as Rivfloza, is generally safe for use. Studies have demonstrated that patients taking this treatment experienced a significant decrease in urinary oxalate levels, which is crucial for managing primary hyperoxaluria, a rare genetic disorder that can lead to kidney stones and kidney damage.

Over a period of more than three years, patients maintained stable kidney function and experienced fewer kidney stones. The most common side effects were mild, including reactions at the injection site. These findings suggest that the treatment is safe for long-term use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for primary hyperoxaluria?

DCR-PHXC is unique because it targets the root cause of primary hyperoxaluria by using RNA interference to reduce the production of oxalate, the compound responsible for the condition. Unlike traditional treatments that primarily focus on managing symptoms or aiding oxalate removal, such as high fluid intake, vitamin B6, or dialysis, DCR-PHXC is administered as a simple monthly subcutaneous injection. Researchers are excited about its potential to offer a more direct and convenient approach to significantly lowering oxalate levels, which could improve patient outcomes and quality of life.

What evidence suggests that DCR-PHXC might be an effective treatment for primary hyperoxaluria?

Research has shown that DCR-PHXC, also known as nedosiran, may help treat primary hyperoxaluria (PH) by significantly lowering oxalate levels in urine. High oxalate levels can lead to kidney stones. Studies found that nedosiran was safe for patients and maintained kidney function for over three years. In addition to reducing kidney stones, the treatment proved effective for both adults and children with various types of PH. These findings strongly suggest that DCR-PHXC could serve as a good long-term treatment for managing PH. ^{2 3 5 6 7}

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. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925001743

PHYOX3: Nedosiran Long-Term Safety and Efficacy in ... Nedosiran was well-tolerated, reduced average Uox levels, reduced kidney stone occurrence, and maintained stable renal function for over 3 years.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04042402

NCT04042402 | Long Term Extension Study in Patients ... To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via change from baseline and abnormal ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/215842Orig1s000IntegratedR.pdf

215842Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov The treatment of primary hyperoxaluria type 1 (PH1) in pediatric ( years of age and older) and adult patients. SNOMED CT code for proposed.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10147791/

Nedosiran in primary hyperoxaluria subtype 3 - PubMed Central This phase I study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous nedosiran in patients with PH subtype 3 (PH3).

5. kidney-international.org kidney-international.org/article/S0085-2538(22)00631-7/fulltext

PHYOX2: a pivotal randomized study of nedosiran in ... Safety, pharmacodynamics, and exposure-response modeling results from a first in human phase 1 study of nedosiran in primary hyperoxaluria.

6. novomedlink.com novomedlink.com/rare-renal-disorders/products/treatments/rivfloza/efficacy-safety.html

Efficacy & Safety | Rivfloza® (nedosiran) injection 80mg ... Patients treated with Rivfloza (nedosiran) injection experienced a substantial reduction in UOx levels.

7. rivfloza.com rivfloza.com/

Primary Hyperoxaluria Type 1 (PH1) Treatment | Rivfloza ... Important Safety Information. What are the possible side effects of Rivfloza®? The most common side effects of Rivfloza® include injection site reactions, such ...