Primary Hyperoxaluria Type 3Phase 1PHYOX4NCT04555486
Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients
A Phase 1 study testing DCR-PHXC and Sterile Normal Saline (0.9% NaCl) in people with Primary Hyperoxaluria Type 3, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 6 sites in 4 countries.
Trial summary
The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Primary Hyperoxaluria Type 3
- What is being tested?
- DCR-PHXC and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 14 Sep 2020to 7 Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Genetically confirmed PH3
- 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 body surface area [BSA] in participants < 18 years of age) on both assessments conducted in the screening period
- Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period
- Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m^2 BSA
- History of at least one stone event within the last 12 months. Stone events are defined as any of the following:
- renal stone requiring medical intervention, e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications;
- stone passage with or without hematuria; or
- renal colic requiring medication.
Who cannot join
- Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)
- Plasma oxalate > 30 μmol/L
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
Clinical Trial Site
Boston, Massachusetts, 02115
Clinical Trial Site
New York, New York, 10016
Clinical Trial Site
Rochester, Minnesota, 55905
About this study
Official 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
The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function.
Read the detailed description
Potential participants are screened over an up-to-35-day period (with an extra 7-day period for participants who are required to repeat screening 24-hour urine collections or initially unanalyzable screening laboratory assessment samples) prior to randomization. Eligible participants will receive a single dose of DCR-PHXC or placebo on Day 1.
In order to maintain the treatment blind, 24-hour urine oxalate (Uox) results that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded.
It is expected that approximately 10 participants will be screened in order to randomize 6 participants (2:1 randomization; 4 nedosiran:2 placebo) to the study.
Following the up-to-6-week screening period, participants will return to the clinic for interim visits up to Day 85. Visits occurring between the Day 1 and the Day 85 visit may be conducted as at-home telemedicine visits at the discretion of the Investigator. The total time on study for each participant is approximately 18 weeks.
- Conditions
- Primary Hyperoxaluria Type 3
- Being tested
- DCR-PHXC, Sterile Normal Saline (0.9% NaCl)
- Keywords
- primary hyperoxaluria, primary hyperoxaluria type 3, primary hyperoxaluria 3, PH, PH type 3, PH3, RNAi, RNAi therapeutic, LDHA, LDH, GalNAc, siRNA, nedosiran, DCR-PHXC
- Medical subject headings
- Hyperoxaluria, Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCR-PHXCDrug
Also called Nedosiran
Intervention, drug, DCR-PHXC
Sterile Normal Saline (0.9% NaCl)Drug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| DCR-PHXC | Experimental | Participants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection. Receives: Drug: DCR-PHXC |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo. Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile of a single dose of DCR-PHXC in PH3 Patients
Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings
Measured: Screening through Day 85
Secondary outcomes (2)
Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients
Measure maximum plasma concentration of DCR-PHXC
Measured: Day 1 (dosing) through Day 29
The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits
Participants must maintain at least a 30% decrease from the average of 2 screening 24-hour Uox values to be considered "responders" to treatment. The proportion of responders to non-responders will be utilize to assess the efficacy of a single dose of DCR-PHXC in PH3 patients.
Measured: After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2020
- Study start14 Sep 2020
- Primary completion7 Sep 2021
- Study completion7 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Hyperoxaluria Type 3Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomly assigned to one of two interventions: the study drug DCR-PHXC (also known as nedosiran) or the placebo comparator Sterile Normal Saline. For every 2 participants that receive DCR-PHXC, 1 participant will receive placebo. Thus, 4 participants are expected to receive DCR-PHXC, and 2 participants are expected to receive placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alexandra Haagensen, MD, MBA, Study director, Dicerna Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04555486
- Sponsor's protocol ID
- DCR-PHXC-104
- Acronym
- PHYOX4
- Status last verified
- Sep 2024
- First submitted
- 2 Sep 2020
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04555486
- Acronym / sponsor ID
- PHYOX4 / DCR-PHXC-104
- Conditions
- Primary Hyperoxaluria Type 3
- Keywords
- primary hyperoxaluria, primary hyperoxaluria type 3, primary hyperoxaluria 3, PH, PH type 3, PH3, RNAi, RNAi therapeutic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 7 Sep 2021 (actual)
- Study completion
- 7 Sep 2021 (actual)
- First posted
- 18 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function.
Detailed description
Potential participants are screened over an up-to-35-day period (with an extra 7-day period for participants who are required to repeat screening 24-hour urine collections or initially unanalyzable screening laboratory assessment samples) prior to randomization. Eligible participants will receive a single dose of DCR-PHXC or placebo on Day 1.
In order to maintain the treatment blind, 24-hour urine oxalate (Uox) results that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded.
It is expected that approximately 10 participants will be screened in order to randomize 6 participants (2:1 randomization; 4 nedosiran:2 placebo) to the study.
Following the up-to-6-week screening period, participants will return to the clinic for interim visits up to Day 85. Visits occurring between the Day 1 and the Day 85 visit may be conducted as at-home telemedicine visits at the discretion of the Investigator. The total time on study for each participant is approximately 18 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomly assigned to one of two interventions: the study drug DCR-PHXC (also known as nedosiran) or the placebo comparator Sterile Normal Saline. For every 2 participants that receive DCR-PHXC, 1 participant will receive placebo. Thus, 4 participants are expected to receive DCR-PHXC, and 2 participants are expected to receive placebo.
| Arm | Type | Receives |
|---|---|---|
| DCR-PHXC | Experimental | Drug: DCR-PHXCParticipants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection. |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl)Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Genetically confirmed PH3
- 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 body surface area [BSA] in participants < 18 years of age) on both assessments conducted in the screening period
- Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period
- Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m^2 BSA
- History of at least one stone event within the last 12 months. Stone events are defined as any of the following:
Key exclusion criteria (2 listed)
- Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)
- Plasma oxalate > 30 μmol/L
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DCR-PHXCAlso: NedosiranIntervention, drug, DCR-PHXC | Drug | DCR-PHXC |
| Sterile Normal Saline (0.9% NaCl)Placebo comparator | Drug | Sterile Normal Saline (0.9% NaCl) |
Primary outcome
Safety profile of a single dose of DCR-PHXC in PH3 Patients
Time frame: Screening through Day 85
Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings
2 secondary outcomes
Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients
Time frame: Day 1 (dosing) through Day 29
The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits
Time frame: After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandra Haagensen, MD, MBA study director
Dicerna Pharmaceuticals
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DCR-PHXC and Sterile Normal Saline (0.9% NaCl) in people with Primary Hyperoxaluria Type 3, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Germany, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety profile of a single dose of DCR-PHXC in PH3 Patients (time frame: Screening through Day 85). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.