An Early Phase Study of DCR-PH1 in Patients with an Inherited Disorder Resulting in Overproduction of Oxalate

Phase 1

• Conditions: Primary Hyperoxaluria Type 1; MedDRA version: 18.0 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2015-003142-51-GB
• Lead Sponsor: Dicerna Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-06
• Study Completion: 2016-10-14
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

1. Male or female, at least 12 years of age at the time of obtaining informed consent.
2. Diagnosis of PH1, confirmed by genotyping for homozygosity or compound heterozygosity in the AGXT gene (historically available genotype information is acceptable for study eligibility).
3. 24-hour urine oxalate excretion = 0.7 mmol per 1.73 m2 BSA.
4. eGFR = 40 mL/min normalized to 1.73 m2 BSA calculated using the Modification of Diet in Renal Disease (MDRD) formula in adults (age = 18 years), or the formula by Schwartz in patients 12 to < 18 years old [Levey et al, 1999; Schwartz et al, 1976; National Kidney Foundation, 2002].
5. Resting pulse oximetry reading of = 92% and resting systolic blood pressure = 100 mm Hg.
6. All patients must have at least three 24-hour urine oxalate measurements done by a central laboratory prior to receiving study drug.
a. Patients who did not participate in PHYOS observational study will be required to have at least three 24-hour urine oxalate measurements during the screening period.
b. Patients who participated in PHYOS but had less than three 24-hour urine oxalate measurements done by a central laboratory, should have the remaining 24-hour urine oxalate assessments during the screening period.
7. Adults must be able to understand and give written informed consent for participation in this study, including all evaluations and procedures as specified by this protocol. Minors (patients <18 years of age, or younger than the age of majority, according to local regulations) must have a parent or guardian who is able to understand and give written informed consent for participation in this study, including all evaluations and procedures as specified by this protocol. Adolescents (12 to < 18 years of age, or older than 12 years but younger than the age of majority, according to local regulations) must be able to provide written assent for participation.

Are the trial subjects under 18? yes
Number of subjects for this age range: 21
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior renal and/or hepatic transplantation.
2. History of clinical signs and symptoms of systemic oxalosis other than nephrolithiasis or nephrocalcinosis.
3. Participation in any clinical study involving administration of any investigational drug within the 30 days before enrollment (NOTE: participation in PHYOS observational study is allowed).
4. Pregnancy or lactation at the time of screening or enrollment.
5. Sexually active females of childbearing potential (FOCBP) who are not using a highly effective contraception method and men with a fertile FOCBP partner who are unable or unwilling to use a highly effective contraception method (see Section 8.4).
6. Patients with a known history of human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus.
7. Moderate or severe hepatic impairment (Child-Pugh class B or C)
8. Liver function test abnormalities: alanine transaminase (ALT) and/or aspartate transaminase (AST) > 2 times upper limit of normal (ULN).
9. Active alcohol or substance abuse within 60 days prior to enrollment.
10. Prolonged QTc = 450 msec for males or QTc = 470 msec for females, at baseline as assessed by either Bazett’s or Fredericia’s correction methods.
11. Clinically significant prior cardio-respiratory disease, such as myocardial infarction within 6 months due to obstructive coronary artery disease, third degree atrioventricular block or uncontrolled rhythm disturbances, active cardiomyopathy (i.e., symptomatic left ventricular dysfunction), or chronic heart failure (CHF) New York Heart Association (NYHA) Class =III, or documented moderate or more severe chronic obstructive pulmonary disease (COPD) (ie forced expiratory volume in during the first second [FEV1] < 80% predicted).
12. Major surgery or interventional procedure within 30 days prior to study entry, or patients with an inadequate recovery from any surgical or interventional procedure.
13. History of severe reaction to a liposomal product or a known hypersensitivity to lipid products. For Part B (MAD portion), patients with a Grade 3 or higher adverse reaction during Part A (SAD portion) will not be eligible to participate.
14. Unable to collect 24-hour urine samples or follow other study procedures.
15. Any disorder or alteration in mental status that would preclude understanding of the informed consent process and/or completion of the study-related evaluations.
16. Any significant illness, organ system dysfunction, or other condition that, in the opinion of the Investigator, would interfere with the patient’s ability to comply with the protocol requirements, including the ability to attend all visits and undergo all assessments.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified