A Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)

Primary Hyperoxaluria Type 1 Clinical Trial

Official title:

A Phase 1 Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02795325
• Other study ID #: DCR-PH1-101
• Status: Terminated
• Phase: Phase 1
• Start date: May 13, 2016
• Est. completion date: October 14, 2016

Study information

• Verified date: December 2017
• Source: Dicerna Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: October 14, 2016
• Est. primary completion date: October 14, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria Type 1

Intervention

Drug:
• DCR-PH1
IV infusion of DCR-PH1

Other:
• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Germany,  Netherlands, 

References & Publications (3)

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. — View 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. — View Citation

Milliner DS. siRNA Therapeutics for Primary Hyperoxaluria: A Beginning. Mol Ther. 2016 Apr;24(4):666-7. doi: 10.1038/mt.2016.50. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs)		Through Day 29
Secondary	Profile of pharmacokinetics (PK) of DCR-PH1 - Cmax		Through Day 29
Secondary	Profile of pharmacokinetics (PK) of DCR-PH1 - tmax		Through Day 29
Secondary	Profile of pharmacokinetics (PK) of DCR-PH1 - AUC		Through Day 29
Secondary	Profile of pharmacokinetics (PK) of DCR-PH1 - t½		Through Day 29
Secondary	The effect of DCR-PH1 on plasma glycolate levels		Through Day 29
Secondary	The effect of DCR-PH1 on urine glycolate levels		Through Day 29
Secondary	The effect of DCR-PH1 on plasma oxalate levels		Through Day 29
Secondary	The effect of DCR-PH1 on urine oxalate levels		Through Day 29

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