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Trial details
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
Current status:
Approved
|
Date registered:
27/04/2020
|
Date last updated:
03/04/2020
Trial version(s)
History: 19/03/2020
Current: 19/03/2020
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2020043435
Protocol number
DCR-PHXC-201
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Study registered in clinicaltrials.gov
Type of registration
Prospective
Date of registration in national regulatory agency
15/02/2019
Primary sponsor
Dicerna Pharmaceuticals, Inc
Primary sponsor: Country of origin
US
Public title
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
Acronym
Scientific title
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
Acronym
PHYOX2
Brief summary of the study: English
This is a 6-month randomized, placebo-controlled, double-blind study of DCR-PHXC in patients with primary hyperoxaluria (PH1 and PH2). Potential participants are screened over an up-to- 6-week period prior to randomization to DCR-PHXC or placebo. The proposed study is designed to evaluate the efficacy, safety, tolerability, and PK of DCR-PHXC versus placebo in patients with PH1 and PH2.
Brief summary of the study: Arabic
دراسة مدتها 6 أشهر ، في المرحلة الثانية، متعددة المراكز ومزدوجة التعمية، محكومة بدواء وهمي لتقييم فعالية و سلامة محلول الحقن DCR-PHXC (تحت الجلد) ودرجة تحمله لدى المرضى الذين يعانون من فرط أوكسالات البول الأولي
Health conditions/problem studied: Specify
DCR-PHXC is designed to selectively reduce LDHA messenger ribonucleic acid (mRNA) and lactate dehydrogenase (LDH) activity in the liver, and subsequently decrease liver oxalate production. DCR-PHXC is being developed as a treatment for PH, an ultra-rare autosomal recessive disease characterized by excessive production of oxalate in the liver.
Interventions: Specify
DCR-PHXC is a synthetic RNAi drug that consists of a double-stranded oligonucleotide conjugated to GalNAc ligands. DCR-PHXC is a sterile formulation of drug substance (DCR-L1360) in WFI, intended for SC administration. DCR-PHXC is not commercially available in any country. The placebo comparator is 0.9% normal saline for injection.
Key inclusion and exclusion criteria: Inclusion criteria
• 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m2 body surface area [BSA] in participants < 18 years of age) in both collections performed in the screening period. Of the first 24 participants enrolled, at least 12 (50%) must have at least one 24-hour Uox excretion ≥ 1.6 mmol (adjusted per 1.73 m2 BSA in participants aged < 18 years). • Less than 20% variation between the two 24-hour urinary creatinine excretion values [mmol/24 hr/kg] derived from the two 24-hour urine collections in the screening period. • Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min normalized to 1.73 m2 BSA calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula in participants aged ≥ 18 years (Levey & Stevens, 2010), or the formula by Schwartz in participants aged 6 to 17 years, (Schwartz et al., 2009; National Kidney Foundation, 2002). In Japan, the formula by Uemura et al. will be used for participants aged 6 to 17 years.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
6
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
• Renal or hepatic transplantation (prior or planned within the study period) • Current dialysis or anticipated requirement for dialysis during the study period • Plasma oxalate > 30 μmol/L • Documented evidence of clinical manifestations of systemic oxalosis (including preexisting retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations) • Liver function test (LFT) abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) for age and gender.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Other
Trial scope: Specify scope
Efficacy, safety and tolerability
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
DCR-PHXC
Year of authorization
2020
Month of authorization
1
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical – Chemical
Pharmaceutical class
Synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc .
Therapeutic indication
DCR-PHXC is designed to selectively reduce LDHA messenger ribonucleic acid (mRNA) and lactate dehydrogenase (LDH) activity in the liver, and subsequently decrease liver oxalate production. DCR-PHXC is being developed as a treatment for PH, an ultra-rare autosomal recessive disease characterized by excessive production of oxalate in the liver.
Therapeutic benefit
Patients with PH are predisposed to the development of multiple and recurrent urinary tract (urolithiasis) and kidney (nephrolithiasis) stones. This deposition of calcium oxalate in the renal parenchyma produces tubular toxicity and renal damage. At present, no therapies are approved by regulatory authorities for the treatment of patients with PH. A number of supportive therapies are used in an attempt to mitigate some of the effects of the disease. DCR-PHXC treatment has the potential benefit to reduce or eliminate the excess oxalate production in the liver and thus avoid the need for a combined liver and kidney transplantation in patients not already on renal replacement therapy.
Biospecimen retention
Samples with DNA**
Biospecimen description
Samples may be stored for a maximum of 5years (or according to local regulations) following the last participant’s last visit for the study at a facility selected by the sponsor to enable further analysis of immune responses to DCR-PHXC.
Target sample size
36
Actual enrollment target size
Date of first enrollment: Type
Actual
Date of first enrollment: Date
28/10/2019
Date of study closure: Type
Actual
Date of study closure: Date
30/01/2021
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
Participants will be assigned a unique identifier by the Sponsor. Any participant records or data sets that are transferred to the Sponsor will contain the identifier only; participant names or any information which would make the participant identifiable will not be transferred
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
1. US NCT
NCT03847909
2. WHO Universal
U1111-1224-6881
Sources of Monetary or Material Support
Name
Dicerna pharmaceuticals inc. 87 Cambridgepark Drive Cambridge, MA 02140 US
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Chadi
Safa
Beirut
Lebanon
0096171251819
chadi.safa@clinart.net
Clinart Mena
Scientific
Chebl
Mourani
Beirut
Lebanon
009611290090
cheblmourani@gmail.com
Hotel Dieu de France
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu De France
Chebl Mourani
Pediatric Nephrology
Approved
Saint George University Hospital
Pauline Abou Jaoude
Pediatric Nephrology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
01/10/2019
Nancy Alam
nancy.alam@usj.edu.lb
01421000
Saint George Hospital University Medical Center
29/11/2019
Sandra Berberi
smberbari@stgeorgehospital.org
01 1 44 16 30
Countries of Recruitment
Name
Australia
Canada
France
Germany
Italy
Japan
Netherlands
New Zealand
Poland
Romania
Spain
United Kingdom
United States of America
Lebanon
Health Conditions or Problems Studied
Condition
Code
Keyword
Primary Hyperoxaluria
Nephrotic syndrome, other (N04.8)
PHYOX
Interventions
Intervention
Description
Keyword
DCR-PHXC
DCR-PHXC is a synthetic RNAi drug that consists of a double-stranded oligonucleotide conjugated to GalNAc ligands. DCR-PHXC is a sterile formulation of drug substance (DCR-L1360) in WFI, intended for SC administration. DCR-PHXC is not commercially available in any country.
DCR-PHXC
Placebo
The placebo comparator is 0.9% normal saline for injection.
Placebo
Primary Outcomes
Name
Time points
Measure
To assess the efficacy of DCR-PHXC in reducing urinary oxalate burden in patients with PH (types 1 and 2)
The proportion of participants with a reduction from baseline in 24-hour Uox of at least 70%, based on a TWS AUC and/or reaching normalization or near-normalization of 24-hour Uox on at least 2 consecutive visits, starting from Day 90. Normalization of Uox is defined as < 0.46 mmol/24 hours; near-normalization is defined as ≥ 0.46 to < 0.60 mmol/24 hours (values adjusted per 1.73 m2 BSA in participants aged < 18 years).
24-hour Uox
Key Secondary Outcomes
Name
Time points
Measure
To evaluate the effect of DCR-PHXC on stone burden in patients with PH
Percent change in the summed surface area and number of kidney stones identified via kidney ultrasound from Baseline to Day 180
Number of Kidney stone
To evaluate the effect of DCR-PHXC on plasma oxalate in patients with PH
Percent change in plasma oxalate from Baseline to Day 180 (for adults only)
Plasma Oxalate
To evaluate the effect of DCR-PHXC on eGFR
Rate of change in eGFR from Baseline to Day 180
eGFR
To assess the safety of DCR-PHXC in patients with PH
AE and SAE; change from Baseline in 12-lead ECG, physical examination findings, vital signs, and clinical laboratory tests
12 Lead ECG, Physical Examination test, Vital signs, Clinical Laboratory test.
To characterize the PK of DCR-PHXC in patients with PH
Population and individual PK parameters for DCR-PHXC
PK
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial