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

Study Overview
=================
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)

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

Conditions
-----------------
Primary Hyperoxaluria Type 1

Intervention / Treatment
-----------------
* Drug: DCR-PH1
* Other: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PH Patients<br> | Drug: DCR-PH1<br>* IV infusion of DCR-PH1<br>|
| Experimental: Healthy Volunteers<br> | Drug: DCR-PH1<br>* IV infusion of DCR-PH1<br>Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of DCR-PH1 evaluated by the proportion of subjects that experience adverse events (AEs) |  | Through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| The effect of DCR-PH1 on urine glycolate levels |  | Through Day 29 | 
| The effect of DCR-PH1 on plasma oxalate levels |  | Through Day 29 | 
| The effect of DCR-PH1 on urine oxalate levels |  | Through Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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