A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 - Clinical Trial for Primary Hyperoxaluria Type 1 (PH1) | NCT03847909

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Primary Purpose

Status

Completed

Phase

Phase 2

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 1 (PH1) focused on measuring PH1, PH2, Primary Hyperoxaluria, RNAi, RNAi therapeutic, GalNAc, LDHA gene, LDH, siRNA

Eligibility Criteria

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

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DCR-PHXC

Placebo - Sterile Normal Saline (0.9% NaCl)

Arm Description

Intervention, drug, DCR-PHXC

Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Percent change in the summed surface area and number of kidney stones identified via kidney ultrasound from baseline to Day 180

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

Rate of change in eGFR from baseline to Day 180

AE and SAE throughout the study

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.

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.

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.

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.

To characterize the PK of DCR-PHXC in PH patients

Maximum observed plasma concentration (Cmax)

To characterize the PK of DCR-PHXC in PH patients

Area under the plasma concentration versus time curve (AUC)

Full Information

NCT ID

NCT03847909

First Posted

February 15, 2019

Last Updated

June 20, 2022

Sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

1. Study Identification

Unique Protocol Identification Number

NCT03847909

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

October 28, 2019 (Actual)

Primary Completion Date

June 21, 2021 (Actual)

Study Completion Date

June 29, 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

No

Data Monitoring Committee

Yes

5. Study Description

Brief 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)

6. Conditions and Keywords

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

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

Keywords

PH1, PH2, Primary Hyperoxaluria, RNAi, RNAi therapeutic, GalNAc, LDHA gene, LDH, siRNA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DCR-PHXC

Arm Type

Experimental

Arm Description

Intervention, drug, DCR-PHXC

Arm Title

Placebo - Sterile Normal Saline (0.9% NaCl)

Arm Type

Placebo Comparator

Arm Description

Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection

Intervention Type

Drug

Intervention Name(s)

DCR-PHXC

Other Intervention Name(s)

nedosiran

Intervention Description

Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection

Intervention Type

Drug

Intervention Name(s)

Sterile Normal Saline (0.9% NaCl)

Intervention Description

Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo

Primary Outcome Measure Information:

Title

Area under the curve (AUC) of percent change from baseline in 24-hour urinary oxalate excretion between Day 90 and Day 180

Description

Four measurements of percent change from baseline in 24-hour urinary oxalate are combined to determine a single AUC value

Time Frame

3 months (Last 3 months of the 6 month treatment period)

Secondary Outcome Measure Information:

Title

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

Time Frame

3 months (Last 3 months of the 6 month treatment period)

Title

Percent change in the summed surface area and number of kidney stones identified via kidney ultrasound from baseline to Day 180

Time Frame

6 months

Title

Percent change from baseline to Day 180 in plasma oxalate (for adults only)

Description

Four measurements of percent change from baseline in plasma oxalate are combined to determine a single AUC value

Time Frame

6 months

Title

Rate of change in eGFR from baseline to Day 180

Time Frame

6 months

Title

AE and SAE throughout the study

Time Frame

6 months

Title

Change from baseline in 12-lead ECG

Description

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.

Time Frame

6 months

Title

The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings

Description

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.

Time Frame

6 months

Title

The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs

Description

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.

Time Frame

6 months

Title

The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)

Description

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.

Time Frame

6 months

Title

To characterize the PK of DCR-PHXC in PH patients

Description

Maximum observed plasma concentration (Cmax)

Time Frame

6 months

Title

To characterize the PK of DCR-PHXC in PH patients

Description

Area under the plasma concentration versus time curve (AUC)

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexandra Haagensen, MD

Organizational Affiliation

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

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

Minneapolis

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

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Clinical Trial Site

City

Parkville

ZIP/Postal Code

3052

Country

Australia

Facility Name

Clinical Trial Site

City

Hamilton

Country

Canada

Facility Name

Clinical Trial Site

City

Bron

Country

France

Facility Name

Clinical Trial Site

City

Paris

ZIP/Postal Code

75019

Country

France

Facility Name

Clinical Trial Site

City

Bonn

ZIP/Postal Code

53127

Country

Germany

Facility Name

Clinical Trial Site

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Clinical Trial Site

City

Jerusalem

ZIP/Postal Code

9103102

Country

Israel

Facility Name

Clinical Trial Site

City

Roma

ZIP/Postal Code

00165

Country

Italy

Facility Name

Clinical Trial Site

City

Nagoya

ZIP/Postal Code

467-8601

Country

Japan

Facility Name

Clinical Trial Site

City

Tochigi

ZIP/Postal Code

329-0431

Country

Japan

Facility Name

Clinical Trial Site

City

Tokyo

ZIP/Postal Code

183-8561

Country

Japan

Facility Name

Clinical Trial Site

City

Beirut

ZIP/Postal Code

2807

Country

Lebanon

Facility Name

Clinical Trial Site

City

Beirut

Country

Lebanon

Facility Name

Clinical Trial Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Clinical Trial Site

City

Auckland

Country

New Zealand

Facility Name

Clinical Trial Site

City

Białystok

Country

Poland

Facility Name

Clinical Trial Site

City

Bucharest

Country

Romania

Facility Name

Clinical Trial Site

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Clinical Trial Site

City

Santa Cruz

ZIP/Postal Code

38320

Country

Spain

Facility Name

Clinical Trial Site

City

Birmingham

Country

United Kingdom

Facility Name

Clinical Trial Site

City

London

ZIP/Postal Code

WCIN 3JH

Country

United Kingdom

Facility Name

Clinical Trial Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

No

A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (PHYOX2)

Primary Hyperoxaluria Type 1 (PH1), Primary Hyperoxaluria Type 2 (PH2), Kidney Diseases

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial