Back to results

Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients (PHYOX4)

Primary Purpose

Primary Hyperoxaluria Type 3

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

DCR-PHXC

Sterile Normal Saline (0.9% NaCl)

About this trial

This is an interventional treatment trial for Primary Hyperoxaluria Type 3 focused on measuring primary hyperoxaluria, primary hyperoxaluria type 3, primary hyperoxaluria 3, PH, PH type 3, PH3, RNAi, RNAi therapeutic, LDHA, LDH, GalNAc, siRNA, nedosiran, DCR-PHXC

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Genetically confirmed PH3
24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 body surface area [BSA] in participants < 18 years of age) on both assessments conducted in the screening period
Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period
Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m^2 BSA
History of at least one stone event within the last 12 months. Stone events are defined as any of the following:
- renal stone requiring medical intervention, e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications;
- stone passage with or without hematuria; or
- renal colic requiring medication.

Key Exclusion Criteria:

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)
Plasma oxalate > 30 μmol/L

Sites / Locations

Clinical Trial Site
Clinical Trial Site
Clinical Trial Site
Clinical Trial Site
Clinical Trial Site
Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DCR-PHXC

Sterile Normal Saline (0.9% NaCl)

Arm Description

Participants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection.

Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo.

Outcomes

Primary Outcome Measures

Safety profile of a single dose of DCR-PHXC in PH3 Patients

Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings

Secondary Outcome Measures

Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients

Measure maximum plasma concentration of DCR-PHXC

The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits

Participants must maintain at least a 30% decrease from the average of 2 screening 24-hour Uox values to be considered "responders" to treatment. The proportion of responders to non-responders will be utilize to assess the efficacy of a single dose of DCR-PHXC in PH3 patients.

Full Information

NCT ID

NCT04555486

First Posted

September 2, 2020

Last Updated

September 9, 2021

Sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

1. Study Identification

Unique Protocol Identification Number

NCT04555486

Brief Title

Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients

Acronym

PHYOX4

Official Title

A Phase 1 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of DCR-PHXC in Patients With Primary Hyperoxaluria Type 3

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

September 14, 2020 (Actual)

Primary Completion Date

September 7, 2021 (Actual)

Study Completion Date

September 7, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function.

Detailed Description

Potential participants are screened over an up-to-35-day period (with an extra 7-day period for participants who are required to repeat screening 24-hour urine collections or initially unanalyzable screening laboratory assessment samples) prior to randomization. Eligible participants will receive a single dose of DCR-PHXC or placebo on Day 1. In order to maintain the treatment blind, 24-hour urine oxalate (Uox) results that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded. It is expected that approximately 10 participants will be screened in order to randomize 6 participants (2:1 randomization; 4 nedosiran:2 placebo) to the study. Following the up-to-6-week screening period, participants will return to the clinic for interim visits up to Day 85. Visits occurring between the Day 1 and the Day 85 visit may be conducted as at-home telemedicine visits at the discretion of the Investigator. The total time on study for each participant is approximately 18 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Hyperoxaluria Type 3

Keywords

primary hyperoxaluria, primary hyperoxaluria type 3, primary hyperoxaluria 3, PH, PH type 3, PH3, RNAi, RNAi therapeutic, LDHA, LDH, GalNAc, siRNA, nedosiran, DCR-PHXC

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Participants are randomly assigned to one of two interventions: the study drug DCR-PHXC (also known as nedosiran) or the placebo comparator Sterile Normal Saline. For every 2 participants that receive DCR-PHXC, 1 participant will receive placebo. Thus, 4 participants are expected to receive DCR-PHXC, and 2 participants are expected to receive placebo.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DCR-PHXC

Arm Type

Experimental

Arm Description

Arm Title

Sterile Normal Saline (0.9% NaCl)

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo.

Intervention Type

Drug

Intervention Name(s)

DCR-PHXC

Other Intervention Name(s)

Nedosiran

Intervention Description

Intervention, drug, DCR-PHXC

Intervention Type

Drug

Intervention Name(s)

Sterile Normal Saline (0.9% NaCl)

Intervention Description

Placebo comparator

Primary Outcome Measure Information:

Title

Safety profile of a single dose of DCR-PHXC in PH3 Patients

Description

Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings

Time Frame

Screening through Day 85

Secondary Outcome Measure Information:

Title

Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients

Description

Measure maximum plasma concentration of DCR-PHXC

Time Frame

Day 1 (dosing) through Day 29

Title

The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits

Description

Time Frame

After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Genetically confirmed PH3 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 body surface area [BSA] in participants < 18 years of age) on both assessments conducted in the screening period Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m^2 BSA History of at least one stone event within the last 12 months. Stone events are defined as any of the following: renal stone requiring medical intervention, e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications; stone passage with or without hematuria; or renal colic requiring medication. Key Exclusion Criteria: 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) Plasma oxalate > 30 μmol/L

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexandra Haagensen, MD, MBA

Organizational Affiliation

Dicerna Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Trial Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Clinical Trial Site

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Clinical Trial Site

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Clinical Trial Site

City

Bonn

ZIP/Postal Code

53127

Country

Germany

Facility Name

Clinical Trial Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Clinical Trial Site

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients

We'll reach out to this number within 24 hrs