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

NCT02795325 | Terminated Phase 1

• 1 other identifier: DCR-PH1-101
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 2

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)

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

Outcome Measures

Primary Outcomes (1)

• The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs)

  Through Day 29

Secondary Outcomes (8)

• Profile of pharmacokinetics (PK) of DCR-PH1 - Cmax

  Through Day 29

• Profile of pharmacokinetics (PK) of DCR-PH1 - tmax

  Through Day 29

• Profile of pharmacokinetics (PK) of DCR-PH1 - AUC

  Through Day 29

• Profile of pharmacokinetics (PK) of DCR-PH1 - t½

  Through Day 29

• The effect of DCR-PH1 on plasma glycolate levels

  Through Day 29

Study Arms (2)

PH Patients

EXPERIMENTAL

Drug: DCR-PH1

Healthy Volunteers

EXPERIMENTAL

Drug: DCR-PH1; Other: Placebo

Interventions

DCR-PH1 DRUG

IV infusion of DCR-PH1

Healthy Volunteers; PH Patients

Placebo OTHER

Healthy Volunteers

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 12 years of age
• Diagnosis of PH1, confirmed by genotyping
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (2)

Unknown Facility

Bonn, Germany

Location

Unknown Facility

Amsterdam, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 26689264 BACKGROUND

• 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.

  PMID: 27081720 BACKGROUND

• 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.

  PMID: 26758691 BACKGROUND

Related Links

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MeSH Terms

Conditions

Primary hyperoxaluria type 1; Kidney Calculi; Genetic Diseases, Inborn; Metabolic Diseases; Urologic Diseases; Hyperoxaluria

Condition Hierarchy (Ancestors)

Nephrolithiasis; Kidney Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: June 10, 2016
• Study Start: May 13, 2016
• Primary Completion: October 14, 2016
• Study Completion: October 14, 2016
• Last Updated: July 11, 2024

Record last verified: 2024-07

Locations

NL (1); DE (1)