A Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)
Primary Purpose
Primary Hyperoxaluria Type 1
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DCR-PH1
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Primary Hyperoxaluria Type 1 focused on measuring Primary Hyperoxaluria Type 1, PH1, Calcium Oxalate Stones, Kidney Stones, Liver Enzyme Deficiency, Genetic Diseases, Inborn Kidney Diseases, Metabolic Diseases, Inborn Errors, Urological Diseases, Carbohydrate Metabolism, Hyperoxaluria, AGT, RNAi, siRNA, DCR-PH1
Eligibility Criteria
Inclusion Criteria:
- Male or female, at least 12 years of age
- Diagnosis of PH1, confirmed by genotyping
- 24-hour urine oxalate excretion as defined in the protocol
- eGFR ≥ 40 mL/min normalized to 1.73 m2 BSA
- Written informed consent for adults (≥18 years old, or per local regulatory requirement); written informed assent for adolescents (12 to <18 years old, or per local regulatory requirement)
Exclusion Criteria:
- Prior renal and/or hepatic transplantation
- Participation in any clinical study involving administration of any investigational drug within the 30 days before enrollment
- Pregnancy or lactation at the time of screening or enrollment
- Women of child-bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
- Patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus or hepatitis C virus
- Moderate to severe liver impairment
- Liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) > 2 times upper limit of normal (ULN)
- History of severe reaction to a liposomal product or a known hypersensitivity to lipid products.
- Unable to collect required study samples or follow study procedures
- No clinically significant health concerns
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
PH Patients
Healthy Volunteers
Arm Description
Outcomes
Primary Outcome Measures
The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs)
Secondary Outcome Measures
Profile of pharmacokinetics (PK) of DCR-PH1 - Cmax
Profile of pharmacokinetics (PK) of DCR-PH1 - tmax
Profile of pharmacokinetics (PK) of DCR-PH1 - AUC
Profile of pharmacokinetics (PK) of DCR-PH1 - t½
The effect of DCR-PH1 on plasma glycolate levels
The effect of DCR-PH1 on urine glycolate levels
The effect of DCR-PH1 on plasma oxalate levels
The effect of DCR-PH1 on urine oxalate levels
Full Information
NCT ID
NCT02795325
First Posted
May 18, 2016
Last Updated
October 1, 2018
Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
1. Study Identification
Unique Protocol Identification Number
NCT02795325
Brief Title
A Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)
Official Title
A Phase 1 Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Study Start Date
May 13, 2016 (Actual)
Primary Completion Date
October 14, 2016 (Actual)
Study Completion Date
October 14, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
4. Oversight
5. Study Description
Brief Summary
A phase 1 study of DCR-PH1 in patients with primary hyperoxaluria type 1 (PH1) to determine the safety, tolerability, pharmacokinetic (PK) and pharmacodynamics (PD) effects of DCR-PH1 administered via-intravenous infusion (IV)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperoxaluria Type 1
Keywords
Primary Hyperoxaluria Type 1, PH1, Calcium Oxalate Stones, Kidney Stones, Liver Enzyme Deficiency, Genetic Diseases, Inborn Kidney Diseases, Metabolic Diseases, Inborn Errors, Urological Diseases, Carbohydrate Metabolism, Hyperoxaluria, AGT, RNAi, siRNA, DCR-PH1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PH Patients
Arm Type
Experimental
Arm Title
Healthy Volunteers
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
DCR-PH1
Intervention Description
IV infusion of DCR-PH1
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs)
Time Frame
Through Day 29
Secondary Outcome Measure Information:
Title
Profile of pharmacokinetics (PK) of DCR-PH1 - Cmax
Time Frame
Through Day 29
Title
Profile of pharmacokinetics (PK) of DCR-PH1 - tmax
Time Frame
Through Day 29
Title
Profile of pharmacokinetics (PK) of DCR-PH1 - AUC
Time Frame
Through Day 29
Title
Profile of pharmacokinetics (PK) of DCR-PH1 - t½
Time Frame
Through Day 29
Title
The effect of DCR-PH1 on plasma glycolate levels
Time Frame
Through Day 29
Title
The effect of DCR-PH1 on urine glycolate levels
Time Frame
Through Day 29
Title
The effect of DCR-PH1 on plasma oxalate levels
Time Frame
Through Day 29
Title
The effect of DCR-PH1 on urine oxalate levels
Time Frame
Through Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, at least 12 years of age
Diagnosis of PH1, confirmed by genotyping
24-hour urine oxalate excretion as defined in the protocol
eGFR ≥ 40 mL/min normalized to 1.73 m2 BSA
Written informed consent for adults (≥18 years old, or per local regulatory requirement); written informed assent for adolescents (12 to <18 years old, or per local regulatory requirement)
Exclusion Criteria:
Prior renal and/or hepatic transplantation
Participation in any clinical study involving administration of any investigational drug within the 30 days before enrollment
Pregnancy or lactation at the time of screening or enrollment
Women of child-bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
Patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus or hepatitis C virus
Moderate to severe liver impairment
Liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) > 2 times upper limit of normal (ULN)
History of severe reaction to a liposomal product or a known hypersensitivity to lipid products.
Unable to collect required study samples or follow study procedures
No clinically significant health concerns
Facility Information:
City
Bonn
Country
Germany
City
Amsterdam
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
26689264
Citation
Martin-Higueras C, Luis-Lima S, Salido E. Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I. Mol Ther. 2016 Apr;24(4):719-25. doi: 10.1038/mt.2015.224. Epub 2015 Dec 22.
Results Reference
background
PubMed Identifier
27081720
Citation
Milliner DS. siRNA Therapeutics for Primary Hyperoxaluria: A Beginning. Mol Ther. 2016 Apr;24(4):666-7. doi: 10.1038/mt.2016.50. No abstract available.
Results Reference
background
PubMed Identifier
26758691
Citation
Dutta C, Avitahl-Curtis N, Pursell N, Larsson Cohen M, Holmes B, Diwanji R, Zhou W, Apponi L, Koser M, Ying B, Chen D, Shui X, Saxena U, Cyr WA, Shah A, Nazef N, Wang W, Abrams M, Dudek H, Salido E, Brown BD, Lai C. Inhibition of Glycolate Oxidase With Dicer-substrate siRNA Reduces Calcium Oxalate Deposition in a Mouse Model of Primary Hyperoxaluria Type 1. Mol Ther. 2016 Apr;24(4):770-8. doi: 10.1038/mt.2016.4. Epub 2016 Jan 13.
Results Reference
background
Links:
URL
http://www.dicerna.com
Description
Related Info
URL
http://www.rarekidneystones.org
Description
Related Info
URL
http://www.ohf.org
Description
Related Info
URL
http://www.nord.org
Description
Related Info
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A Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)
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