Safety & Tolerability Study of DCR-PHXC in Patients with PH3
Research type
Research Study
Full title
A Phase 1 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of DCR-PHXC in Patients with Primary Hyperoxaluria Type 3
IRAS ID
279442
Contact name
Shabbir Moochhala
Contact email
Sponsor organisation
Dicerna Pharmaceuticals, Inc
Eudract number
2020-000344-67
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
n/a, n/a
Duration of Study in the UK
0 years, 7 months, 8 days
Research summary
Summary of Research
Participants in this study have Primary Hyperoxaluria Type 3 (PH3). This is an inherited disease where lack of function of a particular liver enzyme causes the body to accumulate excess amounts of a substance called oxalate. Oxalate leads to a build-up of insoluble calcium salts in the kidneys. People with PH3 are at increased risk for developing kidney stones. Symptoms can develop at any time from infancy to adulthood. Most individuals are diagnosed with PH3 in childhood or early adulthood. Affected individuals may develop kidney stones at any age, and sometimes by the age of 5 years. Kidney function can be impacted by frequent kidney stones. Over time kidney function may become compromised from frequent stones and/or too much calcium deposited in the kidneys, resulting in chronic kidney disease.Currently there is no approved therapy for the treatment of patients with PH3. Supportive therapies, such as drinking plenty of water and dietary restrictions of foods high in oxalate, are used to help lower oxalate levels and inhibit the formation of kidney stones.
In this study, the study drug, DCR-PHXC, is being assessed to see if a single dose works as anticipated in reducing excess levels of oxalate in patients with PH3, and to determine how safe and well-tolerated this single dose will be.
Summary of Results
A Study of the Safety and Effects of a New Medicine for Children and Adults with Primary Hyperoxaluria Type 3 About this summary This summary gives the public information about a research study called a ‘clinical trial’. It is also written for people who took part in the study.
The full results of the research study are described in a long report - for researchers, health professionals, and for people who approve medicines. This document is a summary of that report.
These results are for this study only. Other studies may show different results.
Thank you to the people who took part in the study and staff who made this study possible.
1
General information about the study
When and where did the study take place?
The study took place from January 2021 to September 2021.
The study was done in 3 countries:
• European Union (EU): 1 site in the Netherlands 1 site in Germany • Outside the EU: 2 sites in the United States Why is this study important?
Primary hyperoxaluria, also known as PH, is a rare, sometimes life-threatening disease. There are 3 types of PH. Each type has a slightly different cause. This was a study in PH Type 3 (PH3).
The liver produces a substance called oxalate. Oxalate is a body waste product, not needed in the body. Normally, oxalate is cleared through the kidneys and leaves the body in urine.
In people with PH, their livers produce too much oxalate. Their kidneys cannot clear the extra oxalate. Build-up of oxalate in the kidneys is harmful. It can cause painful kidney stones. These may first occur in infancy or early childhood. Or they may not occur until adulthood.
Over time oxalate build-up may damage the kidneys and can lead to kidney failure. If kidneys fail, oxalate can build up in other organs too. It can cause bone and blood diseases, heart, skin, and eye problems.
The study medicine, nedosiran, was designed to treat all 3 types of PH. It is intended to block the liver from producing too much oxalate.
This study is important because:
• There is no approved treatment for PH3 at this time.
• If the medicine works as planned, it may prevent the first symptoms of the disease. That way, serious problems could be avoided.What did researchers want to find out?
The researchers wanted to learn more about how nedosiran works in the body, how well it helps the liver make less oxalate in patients with PH3 who are at least 6 years of age, and to learn if the study drug is safe to use for the treatment of PH3.
Type of study
This was a ‘phase 1’ study. Phase 1 studies are done to confirm the safety of a study medicine. Phase 1 studies enroll small numbers of participants.
2
Who took part in this study?
The study included 6 people with PH3. Their ages ranged from 12 to 64 years. There were 3 men, 1 boy, and 2 women. Race was reported for 5 of the 6 participants. These 5 were all White.
Participants were from:
• the European Union 1 from the Netherlands 1 from Germany.
• a non-European Union country 4 from the United States To be in the study, participants had to have:
• PH3
• at least 1 kidney stone in the previous year • laboratory results within certain ranges People could not be in the study if they:
• had a kidney or liver transplant or a planned transplant • were on dialysis All 6 participants met these requirements. Of the 6 participants, 4 had normal kidney function, 1 had mild kidney disease and 1 had moderate kidney disease.
3
Which medicines were studied?
The study used 2 medicines:
• nedosiran (also known as DCR-PHXC), given as a shot under the skin of the thigh or belly • placebo, given as a shot that looked just the same but had no active medicine Randomly, like tossing a coin, participants were assigned to 1 of 2 groups.
• 4 got a single shot of nedosiran
• 2 got a single shot of placebo
The dose given to each participant was based on body weight.
Participants did not know which medicine they got. During the study, the researchers did not know either. That way, safety results in the 2 groups could be compared and judged fairly.
4
What were the overall results of the study?
This was a study of a single dose of nedosiran compared with a single dose of placebo.
Over the 18-week study, 8 visits were planned. All of the 6 participants who enrolled completed the study.
• 4 received nedosiran
• 2 received placeboSafety was measured by:
• the number of side effects participants had • changes during the study in participants’:
- lab test results
- blood pressure
- heart rate or pattern of heart beats
- rate of breathing
- body temperature
- physical exam findings
Oxalate levels were measured in urine samples, to find out if oxalate levels would drop for participants given study medicine.
So study results could be judged fairly, goals were planned before the study started. The researchers figured out the amount oxalate would need to drop that would show the study medicine worked. The study goal was for oxalate levels to drop by this pre-set amount on 2 back-to-back visits.
After the study, results were compared between the 2 groups. Based on the results in this study of these participants with PH3, researchers found:
• A single dose of nedosiran given according to body weight was safe.
• Safety results in the nedosiran and placebo groups were similar.
• No participants in the study met the study goal of oxalate levels dropping by the pre-set amount at 2 back-to-back visits.
• 2 participants who got nedosiran met the pre-set drop in oxalate levels at a single visit.
• For participants given nedosiran, oxalate levels generally dropped during the study.
• For participants given placebo, no drop in oxalate levels was seen.
More details about this study are on websites listed in Section 10.
5
What were the side effects?
What are side effects?
Side effects are unwanted medical ‘events’ which the doctor believes may be caused by the medicine in the study.
In this study:
• 3 of the 4 participants who got nedosiran had side effects • both of the 2 participants who got placebo had side effects All side effects were considered mild.
What were the serious side effects?
A side effect is serious if it:
• leads to death,
• is life-threatening,
• puts someone in the hospital or keeps them in the hospital, • causes a birth defect, • causes a disability that lasts a long time or • needs medical or surgical treatment to prevent any of the above, as judged by the doctor.
None of the participants in the study had serious side effects.
What were the most common side effects?
Back pain was reported by 2 participants who got nedosiran. No other side effects were reported for more than one participant.6
How has the study helped people and researchers?
This study is just one of many studies of nedosiran. The studies are done to find out how best to use nedosiran to treat people with PH.
In this study, researchers found that single doses of nedosiran are safe for people aged 6 and older with PH3. Because the study goal for lowering of oxalate levels on back-to-back visits was not met, more research may be needed to learn if nedosiran can help people with PH3.
This study included a small number of participants. These results are for this study only. Other studies may show different results.
7
Are there plans for further studies?
Studies with nedosiran are still going on. Other studies may be planned.
Details on these studies will be posted on the websites listed in Section 10.
8
Study name
Study name: A phase 1 placebo-controlled, double-blind, multi-center study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of DCR-PHXC in patients with primary hyperoxaluria type 3 Phase of clinical development: Phase 1 EudraCT number: 2020-002826-97 National Clinical Trial number: 04555486 IND number: IND 132214
9
Who sponsored the study?
Research sponsor:
Dicerna Pharmaceuticals, Inc.
Contact details of sponsor: Dicerna Pharmaceuticals, Inc. 75 Hayden Avenue Lexington, MA 02421 USA E-mail: medicalinfo@dicerna.com Internet: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.dicerna.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cfcf634e0dcb442c46b7e08da64e903c0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637933249205960293%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=zLWXRVG%2FPhRMaOrgnhOJDxJcKuS15uFNaMHXSRyAjRQ%3D&reserved=010
Where can I find more information?
You can find more information about the study or the medicine at these websites:
• EUs clinical trials register https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cfcf634e0dcb442c46b7e08da64e903c0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637933249205960293%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=XfVMNsszf2UEQNOaUbis0xz0BnpC%2BybjXQetcC90Dtk%3D&reserved=0, (for this study: EudraCT 2020-002826-97) • US government clinical trials website https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cfcf634e0dcb442c46b7e08da64e903c0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637933249206116515%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=S4SA2F3KQ9DJYFmUBmmY1kH70RLAMeWII8kxWiSt%2BQk%3D&reserved=0, (for this study: NCT03847909) For general information about clinical studies please go to:https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.dicerna.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cfcf634e0dcb442c46b7e08da64e903c0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637933249206116515%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=M%2BFxvUZYRkd9WJ90gcaXfgmgow1PDRvAc9fr6PI1f0c%3D&reserved=0
Dicerna Pharmaceuticals, Inc. | Trial ID: DCR-PHXC-104 | Version: 1.0 | Date: 03 Mar 2022 | Page 3 of 5 This document includes known facts as of the time the document was finalized.REC name
London - Riverside Research Ethics Committee
REC reference
20/LO/0889
Date of REC Opinion
7 Aug 2020
REC opinion
Further Information Favourable Opinion