PHYOX 2
Research type
Research Study
Full title
A Phase 2 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of DCR-PHXC Solution for Injection (subcutaneous use) in Patients with Primary Hyperoxaluria
IRAS ID
259136
Contact name
Shabbir Moochhala
Contact email
Sponsor organisation
Dicerna Pharmaceuticals Inc
Eudract number
2018-003098-91
Clinicaltrials.gov Identifier
U1111-1224-6881, WHO Universal Trial Number (UTN); 132214, IND Reference
Duration of Study in the UK
1 years, 6 months, days
Research summary
Research Summary
This is a 6-month study of DCR-PHXC in patients with Primary Hyperoxaluria (PH).
The purpose of this study is to learn more about how DCR-PHXC works in the body, how well it helps the liver make less oxalate to reduce symptoms of PH in patients at least 6 years of age with primary hyperoxaluria type 1 (PH1) or primary hyperoxaluria type 2 (PH2). The study trial will also test if the study medicine is safe to use for the treatment of PH.
About 36 participants will take part in this clinical study at approximately 35 sites worldwide.
In this trial, 2 out of every 3 participants (66%) will receive the study medicine, DCR PHXC, and 1 out of every 3 participants will receive placebo. The placebo comparator is preservative-free normal saline 0.9% solution for subcutaneous (SC) injection.
Placebo or DCR-PHXC will be administered once a month via subcutaneous injection in the thigh or abdomen (an injection just under the skin).It is a blinded study, so neither the participant or study doctor will not know which treatment participant is receiving.
The dose of DCR-PHXC in adults is 170mg. In adolescents (12-17 years old) weighing at least 50 kg will also be 170 mg. For adolescents weighing less than 50 kg, the dose will be 136 mg. In children aged 6 to 11 years of age, the dose of DCR-PHXC will be determined once more data are available from ongoing study.
In order to provide continued patient access to DCR-PHXC and to expand the safety database for the product, a roll-over long-term extension study is planned (DCR-PHXC-301). Participants successfully completing study DCR-PHXC-201 may be screened for entry into the roll-over study at the end of study visit.
Summary of Results
What was this study about?
DCR-PHXC-201 was a 6-month study in PH Type 1 (PH1) and Type 2 (PH2). The researchers wanted to learn if the study medicine (nedosiran) helps the liver to make less oxalate and is safe to use in patients with PH1 or PH2 who are at least 6 years old.
Who took part in this study?
Twenty (20) adults and 15 children participated in this study. Their ages ranged from 9 to 46. Half of the participants were female. Twenty-nine (29) of 35 participants had PH1 and 6 had PH2. Most of the participants had normal kidney function, but some had mild or moderate kidney disease.
Which medicines were studied?
Randomly, like tossing a coin, participants were assigned to 1 of 2 medicine groups. The plan was that out of every 3 participants, 2 would be assigned to get the active study medicine. The actual numbers were that:
• 23 got nedosiran, given as a shot under the skin of the thigh or belly once a month
• 12 got placebo (a shot that looked just the same but had no active medicine)
The dose given to each participant was based on their age and body weight.
Participants did not know which medicine they received. During the study, the researchers did not know either. That way, results in the 2 groups could be compared and judged fairly.
What were the overall results of the study?
Oxalate levels were measured in urine samples to find out if oxalate levels would drop for participants given study medicine. For study results to be judged fairly, research goals were planned before the study started. The study goal was for urine oxalate levels to drop by an average of about 40% over the last 3 months of the study.
After the study, results were compared between the 2 groups and the researchers found that:
• Average levels of oxalate in the urine over the last 3 months of the study were approximately 57% lower in the nedosiran group than in the placebo group.
• Half of all participants in the nedosiran group had urine oxalate levels that were normal or close to normal on 2 back-to-back measurements. No participants in the placebo group had this result. It is important to note that no participants with PH2 in either group had this result.
What were the side effects?
Side effects are unwanted medical ‘events’ that the doctor believes may be caused by the medicine in the study. In this study, more participants in the nedosiran group (44%) had side effects compared to the placebo group (25%). The most common side effects associated with nedosiran were problems (like redness or pain) at the site where the study medicine was injected. These skin problems were mild and went away without treatment.REC name
South Central - Berkshire B Research Ethics Committee
REC reference
19/SC/0035
Date of REC Opinion
8 Apr 2019
REC opinion
Further Information Favourable Opinion