Nedosiran for Primary Hyperoxaluria

(PHYOX8 Trial)

No longer recruiting at 18 trial locations

Overseen By Medical Information

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Must not be taking: RNAi drugs

Disqualifiers: Renal transplant, Dialysis, Severe oxalosis, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called nedosiran for children with Primary Hyperoxaluria, a condition where the body produces excess oxalate, which can form kidney stones. The goal is to evaluate nedosiran's effectiveness in children 11 years old and younger who have this condition but maintain relatively good kidney function. The trial is open to children diagnosed with Primary Hyperoxaluria types 1, 2, or 3, who have been on the same treatment plan for at least three months and are not receiving dialysis. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of children, offering a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

Participants must stay on their current stable treatment regimen for Primary Hyperoxaluria during the study. Dose adjustments for weight gain are allowed.

Is there any evidence suggesting that nedosiran is likely to be safe for humans?

Research has shown that nedosiran is generally safe for people with primary hyperoxaluria. Studies have found that it significantly lowers urine oxalate levels, which can cause kidney stones and other problems. Participants who took nedosiran maintained stable kidney function over a long period.

These results suggest that nedosiran is safe to use, with no major side effects reported in the studies. The treatment is administered as a monthly injection, and patients have managed it well. While this information indicates a good safety record, individual experiences can differ. Always consult healthcare professionals when considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for primary hyperoxaluria focus on managing symptoms and reducing oxalate levels through dietary changes and medications that increase urine output. But nedosiran works differently, targeting the root cause of the condition by inhibiting the enzyme LDH, which plays a crucial role in oxalate production. Researchers are excited about nedosiran because it is administered as a monthly subcutaneous injection, which could offer a more convenient and potentially more effective approach than current therapies. This could mean fewer hospital visits and better quality of life for patients.

What evidence suggests that nedosiran might be an effective treatment for Primary Hyperoxaluria?

Research has shown that nedosiran may help treat primary hyperoxaluria, a condition causing excessive oxalate in the urine, leading to kidney stones and other issues. Studies have found that nedosiran lowers urine oxalate levels, crucial for managing this condition. Specifically, patients who took nedosiran experienced fewer kidney stones and maintained stable kidney function over several years. The treatment was also well-tolerated. These findings suggest that nedosiran could effectively manage primary hyperoxaluria, particularly in maintaining kidney health and reducing complications. ^{1 2 5 6 7}

Who Is on the Research Team?

Sarb Shergill, PhD

Principal Investigator

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day according to the SoA (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.

Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)

Documented diagnosis of PH1 or PH2 or PH3 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).

Exclusion Criteria

- Severe intercurrent illness

Prior renal or hepatic transplantation; or planned transplantation within the study period

Currently receiving dialysis or anticipating requirement for dialysis during the study period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 5 weeks

Treatment

Participants receive monthly subcutaneous injections of DCR-PHXC based on age and weight

24 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• nedosiran

Trial Overview 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.

How Is the Trial Designed?

Group I: Open-Label DCR-PHXC Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Lead Sponsor

Trials

19

Recruited

580+

Dicerna Pharmaceuticals, Inc.

Lead Sponsor

Trials

15

Recruited

500+

Founded

2007

Headquarters

Watertown, USA

Known For

RNA Therapeutics

Top Products

GalXC, GalXC-Plus

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40630298/

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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03847909

NCT03847909 | A Study to Evaluate DCR-PHXC in ... ... data for the primary outcome measure. Whether the clinical study ended ... PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2.

4. 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.

5. academic.oup.com academic.oup.com/ckj/article/18/4/sfae383/7914171

efficacy and safety of RNA interference for the treatment of ... Early RNAi intervention is beneficial for patients, especially in maintaining stable kidney function and reversing the effects of hyperoxaluria.

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

Nedosiran in primary hyperoxaluria subtype 3 - PubMed Central In clinical trials, nedosiran administration resulted in a marked reduction in 24-h urinary oxalate (Uox) and plasma oxalate (Pox) in patients ...

7. 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 incidence ...