Study of nedosiran for patients with primary hyperoxaluria type 1 and severe kidney impairment with or without dialysis

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What is this study about?

This study involves patients with Primary Hyperoxaluria Type 1, a rare genetic condition where the liver produces too much of a substance called oxalate. When oxalate builds up in the body, it can combine with calcium to form crystals that damage the kidneys and other organs. The study focuses on patients who have severe kidney damage from this disease, including those who may need dialysis, which is a treatment that uses a machine to filter waste from the blood when the kidneys can no longer do this properly. The treatment being tested is called DCR-PHXC, also known as nedosiran, which is given as an injection under the skin. This medication is designed to reduce the amount of oxalate that the liver produces.

The purpose of this study is to see how well DCR-PHXC works in lowering the levels of oxalate in the blood and to check how safe it is for patients with Primary Hyperoxaluria Type 1 who have severe kidney problems. The study will measure oxalate levels in the blood at the beginning and then again after 180 days of treatment to see if there is a reduction. The study will also look at whether there are changes in the dialysis schedule that patients need, changes in kidney stones that can be seen on ultrasound scans, which use sound waves to create pictures of the inside of the body, and changes in calcium deposits in the kidneys and heart that occur when oxalate crystals build up in these organs.

During the study, patients will receive regular doses of the medication for up to 60 weeks, with a maximum daily dose of 170 milligrams. The study is open to people of different ages, from newborns to adults, and all participants will receive the active treatment rather than a placebo. Throughout the study period, doctors will monitor how well the treatment works and check for any side effects. The study will continue until the end of 2031 to gather long-term information about the safety and effectiveness of this treatment for patients with this rare kidney disease.

1 Initial treatment period

Your treatment with nedosiran will begin after enrollment in the study. Nedosiran is the active substance being tested in this trial.

The medication will be administered as a solution for injection given under the skin (subcutaneous injection).

The study will evaluate how well nedosiran works in lowering the level of a substance called plasma oxalate in your blood. Plasma oxalate is a waste product that builds up in people with primary hyperoxaluria type 1.

If you are currently receiving hemodialysis (a procedure to filter your blood using a machine) or peritoneal dialysis (a procedure to filter your blood using the lining of your abdomen), your dialysis schedule should remain stable during the study.

2 Assessment at day 180

At day 180 (approximately 6 months after starting treatment), your plasma oxalate levels will be measured to determine how much they have changed from the beginning of the study.

This measurement is the main goal of the study and will help determine whether nedosiran is effective in reducing plasma oxalate levels.

Throughout the treatment period up to day 180, your plasma oxalate levels will be monitored to identify the maximum reduction achieved.

3 Additional assessments during the study

If you are on dialysis, any changes to your dialysis schedule will be recorded during the study.

An ultrasound examination will be performed to check for changes in kidney stones. The amount of stones in your kidneys will be compared from the start of the study to day 180.

Nephrocalcinosis (calcium deposits in the kidneys) will be assessed to see if there are any changes during the study.

Your heart will be evaluated for cardiac oxalosis (oxalate deposits in the heart) to monitor any changes during treatment.

4 Continued monitoring

The study will continue beyond day 180 to monitor the long-term safety and effectiveness of nedosiran.

Regular assessments will be conducted to evaluate how well the medication is working and to monitor for any side effects.

The overall study is expected to continue until the end of 2031, though your individual participation duration will be determined by the study protocol.

Who Can Join the Study?

Participants must be newborns, infants, children, adolescents, or adults of any age from birth onwards
Adolescents who are 12 years or older but younger than 18 years must be able to provide written agreement to participate in the study
For children younger than 12 years, agreement to participate will follow local rules and regulations
Must be affiliated with or covered by a health insurance system, if required by local regulations
Must have a confirmed diagnosis of PH1, which is a rare genetic condition, verified by genotyping, which is a test that examines your genes. Previous genetic test results are acceptable
Must have an estimated GFR, which is a measure of how well the kidneys are filtering waste from the blood, of less than 30 at the screening visit. This number is adjusted for body size. For infants younger than 12 months, blood levels of a waste product called creatinine must be higher than normal
Must have an average of 2 blood tests showing plasma oxalate levels, which is a substance that can build up in the body, greater than 20 during the screening period
If receiving hemodialysis, which is a treatment that filters waste from blood using a machine, or peritoneal dialysis, which uses the lining of the abdomen to filter waste, the treatment must have been ongoing for 24 months or less and must have been stable for at least 2 weeks before screening
Can be male or female
Male participants with female partners who can become pregnant must agree to use birth control during treatment and for at least 12 weeks after the last dose, and must not donate sperm during this time
Female participants must not be pregnant or breastfeeding, and must either be unable to become pregnant or agree to use birth control for 4 weeks before starting the study, during treatment, and for at least 12 weeks after the last dose. They must also agree not to harvest or freeze eggs during this time
The participant, or their parent or legal guardian if the participant is a minor, must be able to provide signed agreement to participate and follow all study requirements and restrictions

Who Cannot Join the Study?

No exclusion criteria have been specified for this clinical trial in the available information.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Kllwzgedimlixoljrvh Bvqs	Bonn	Germany
Hqevicum Vslq dkombawe	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Germany	Recruiting	01.02.2021
Italy	Not recruiting	01.02.2021
Spain	Recruiting	01.02.2021

Trial locations

Investigated drugs:

Nedosiran

DCR-PHXC is an investigational medication being studied for the treatment of Primary Hyperoxaluria Type 1, a rare genetic condition that causes the body to produce too much oxalate. This medication is designed to help lower the levels of oxalate in the blood of patients who have severe kidney problems, including those who may be on dialysis. The goal of this treatment is to reduce the harmful buildup of oxalate that can damage organs and tissues in people with this condition.

Primary Hyperoxaluria – Primary Hyperoxaluria is a rare inherited disorder that affects the way the body processes a substance called oxalate. The condition occurs when the liver produces too much oxalate due to a genetic defect in certain enzymes. Excess oxalate combines with calcium in the urine to form crystals and stones in the kidneys. Over time, these crystals can build up in the kidneys and damage kidney tissue, leading to reduced kidney function. As the disease progresses, oxalate crystals may also deposit in other organs and tissues throughout the body, including the heart, bones, eyes, and blood vessels. When kidney function becomes severely impaired, patients may require dialysis to remove waste products from their blood.

Trial ID:

2024-512259-19-00

Protocol code:

DCR-PHXC-204

NCT ID:

NCT04580420

Trial Phase:

Therapeutic exploratory (Phase II)

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Study of nedosiran for patients with primary hyperoxaluria type 1 and severe kidney impairment with or without dialysis

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