Clinical trial NCT02795325: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-06-10
Enrollment: 41
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs)
timeFrame: Through Day 29
Secondary outcomes:
measure: Profile of pharmacokinetics (PK) of DCR-PH1 - Cmax
timeFrame: Through Day 29
measure: Profile of pharmacokinetics (PK) of DCR-PH1 - tmax
timeFrame: Through Day 29
measure: Profile of pharmacokinetics (PK) of DCR-PH1 - AUC
timeFrame: Through Day 29
measure: Profile of pharmacokinetics (PK) of DCR-PH1 - t½
timeFrame: Through Day 29
measure: The effect of DCR-PH1 on plasma glycolate levels
timeFrame: Through Day 29
measure: The effect of DCR-PH1 on urine glycolate levels
timeFrame: Through Day 29
measure: The effect of DCR-PH1 on plasma oxalate levels
timeFrame: Through Day 29
measure: The effect of DCR-PH1 on urine oxalate levels
timeFrame: Through Day 29
Other outcomes:
Locations:
city: Bonn
country: Germany
city: Amsterdam
country: Netherlands
Study officials:
References:
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.
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.
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.