A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2

Kidney Diseases Clinical Trial

— PHYOX2  

Official title:

A Phase 2 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of DCR-PHXC Solution for Injection (Subcutaneous Use) in Patients With Primary Hyperoxaluria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03847909
• Other study ID #: DCR-PHXC-201
• Status: Completed
• Phase: Phase 2
• Start date: October 28, 2019
• Est. completion date: June 29, 2021

Study information

• Verified date: June 2022
• Source: Dicerna Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of DCR-PHXC in Children and Adults with Primary Hyperoxaluria Type 1 (PH1) and Primary Hyperoxaluria Type 2 (PH2)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 29, 2021
• Est. primary completion date: June 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Key Inclusion Criteria:

• Capable and willing to provide written informed consent or assent
• Documented diagnosis of PH1 or PH2, confirmed by genotyping
• Must meet the 24 hour urine oxalate excretion requirements
• Less than 20% variation between the two 24-hour urinary creatinine excretion values derived from the two 24-hour urine collections in the screening period
• Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 BSA

Key Exclusion Criteria:

• Renal or hepatic transplantation (prior or planned within the study period)
• Currently on dialysis or anticipated requirement for dialysis during the study period
• Plasma oxalate >30 µmol/L
• Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)
• Use of an RNA interference (RNAi) drug within the last 6 months
• Participation in any clinical study in which you received an investigational medicinal product (IMP) within 4 months before Screening
• Liver function test (LFT) abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) for age and gender
• Inability or unwillingness to comply with study procedures

Related Conditions & MeSH terms

• Genetic Disease
• Genetic Diseases, Inborn
• Hyperoxaluria, Primary
• Kidney Diseases
• Primary Hyperoxaluria Type 1 (PH1)
• Primary Hyperoxaluria Type 2 (PH2)
• Urologic Diseases

Intervention

Drug:
• DCR-PHXC
Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection
• Sterile Normal Saline (0.9% NaCl)
Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo

Locations

Country	Name	City	State
Australia	Clinical Trial Site	Parkville
Canada	Clinical Trial Site	Hamilton
France	Clinical Trial Site	Bron
France	Clinical Trial Site	Paris
Germany	Clinical Trial Site	Bonn
Germany	Clinical Trial Site	Heidelberg
Israel	Clinical Trial Site	Jerusalem
Italy	Clinical Trial Site	Roma
Japan	Clinical Trial Site	Nagoya
Japan	Clinical Trial Site	Tochigi
Japan	Clinical Trial Site	Tokyo
Lebanon	Clinical Trial Site	Beirut
Lebanon	Clinical Trial Site	Beirut
Netherlands	Clinical Trial Site	Amsterdam
New Zealand	Clinical Trial Site	Auckland
Poland	Clinical Trial Site	Bialystok
Romania	Clinical Trial Site	Bucharest
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Santa Cruz
United Kingdom	Clinical Trial Site	Birmingham
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Minneapolis	Minnesota
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Israel,  Italy,  Japan,  Lebanon,  Netherlands,  New Zealand,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve (AUC) of percent change from baseline in 24-hour urinary oxalate excretion between Day 90 and Day 180	Four measurements of percent change from baseline in 24-hour urinary oxalate are combined to determine a single AUC value	3 months (Last 3 months of the 6 month treatment period)
Secondary	Proportion of participants with a 24-hour Uox level < 0.46 mmol/24 hours or = 0.46 - < 0.60 mmol/24 hours (adjusted per 1.73 m2 BSA in participants aged <18 years) on at least two consecutive study visits commencing at Day 90 and ending at Day 180		3 months (Last 3 months of the 6 month treatment period)
Secondary	Percent change in the summed surface area and number of kidney stones identified via kidney ultrasound from baseline to Day 180		6 months
Secondary	Percent change from baseline to Day 180 in plasma oxalate (for adults only)	Four measurements of percent change from baseline in plasma oxalate are combined to determine a single AUC value	6 months
Secondary	Rate of change in eGFR from baseline to Day 180		6 months
Secondary	AE and SAE throughout the study		6 months
Secondary	Change from baseline in 12-lead ECG	Standard 12-lead ECGs will be performed in the supine position after the subject has rested comfortably for 10 minutes. The parameters assessed will be rhythm, ventricular rate, PR interval, QRS duration, QT interval, and corrected QT interval (QTcF, Fridericia correction). The Investigator or designee is responsible for reviewing the ECG(s) to assess whether the results are within normal limits and to determine the clinical significance of the results.; Standardized ECG acquisition equipment will be provided to all clinical trial sites at the start of the trial, to ensure parity across all sites.	6 months
Secondary	The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings	A full physical examination will include a complete review of body systems: eyes, ears, nose, and throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, and neurological. A full physical exam is done at Screening, Day 180 and if a participant ends the study early.; A brief physical examination will minimally include chest/respiratory, heart/cardiovascular, dermatological/skin, and gastrointestinal/liver. A brief physical examination will be performed may be performed at the Investigator's discretion at all other visits.	6 months
Secondary	The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs	Vital signs include blood pressure, pulse/heart rate, oral body temperature, and respiratory rate.; Parameters will be measured in the supine position, using an automated instrument or manually, after the participant has rested comfortably for 10 minutes. In the pediatric population, an age-appropriate cuff size should be used for blood pressure measurements.; Temperature will be obtained in degrees Celsius (°C), pulse rate will be counted for a full minute and recorded in beats per minute, and respirations will be counted for a full minute and recorded in breaths per minute.	6 months
Secondary	The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)	To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via the change from baseline and incidence of abnormal clinical laboratory tests.	6 months
Secondary	To characterize the PK of DCR-PHXC in PH patients	Maximum observed plasma concentration (Cmax)	6 months
Secondary	To characterize the PK of DCR-PHXC in PH patients	Area under the plasma concentration versus time curve (AUC)	6 months