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Study of DCR-PHXC-101 in Normal Healthy Volunteers and Patients With Primary Hyperoxaluria

Primary Purpose

Primary Hyperoxaluria

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DCR-PHXC
Placebo
Sponsored by
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Hyperoxaluria

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Group A (HVs) Major Inclusion Criteria:

  • Willing and able to provide informed consent and comply with study requirements.
  • Male or female subjects between 18 and 55 years of age, inclusive.
  • Subject must have a body mass index (BMI) 19.0 to 32 kg/m2, inclusive.
  • Non-smokers, at least 1-month tobacco free, and willing to remain tobacco free through end of study (EOS).
  • Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.

Group A (HVs) Major Exclusion Criteria:

  • Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease.
  • Routine or chronic use of more than 3 grams of acetaminophen (Tylenol) daily.
  • History of kidney stones.
  • Use of any investigational agent within 90 days before the first dose of study medication.
  • History of donation of more than 450 mL of blood within 90 days prior to dosing in the clinical research center or planned donation less than 30 days after receiving Investigational Medicinal Product (IMP).
  • Plasma or platelet donation within 7 days of dosing and through EOS.
  • History of reactions to an oligonucleotide-based therapy.
  • Males with female partners who are planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP.
  • Plasma or platelet donation within 7 days of dosing and through EOS.

Group B (PH1 and PH2 patients) Major Inclusion Criteria:

  • Willing and able to provide informed consent and comply with study requirements.
  • Male or female, at least 6 years of age.
  • Minimum body weight of 25 kg.
  • Genetic confirmation of PH1 and PH2 disease.
  • Meet the 24 hour urine oxalate excretion requirements.
  • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.
  • If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 4 weeks.

Group B (PH1 and PH2 patients) Major Exclusion Criteria:

  • Prior renal and/or hepatic transplantation.
  • Currently receiving dialysis.
  • Participation in any clinical study where they received an investigational agent within 4 months before enrollment.
  • Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease.
  • Liver function test (LFT) abnormalities.
  • History of reactions to an oligonucleotide-based therapy.

Sites / Locations

  • Boston Children's Hospital
  • Centre d'Investigation Clinique - CIC 1407 - Hospices Civils de Lyon
  • Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie
  • University of Amsterdam
  • Queen Elizabeth Hospital Birmingham
  • Birmingham Children's Hospital NHS Trust
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Group A Active (DCR-PHXC)

Group A Placebo

Group B Active (DCR-PHXC)

Arm Description

HVs, single ascending doses of DCR-PHXC.

HVs, normal saline 0.9% injection to match active doses.

PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.

Outcomes

Primary Outcome Measures

Number of patients with Treatment-Related Adverse Events (TEAEs)

Secondary Outcome Measures

Full Information

First Posted
December 21, 2017
Last Updated
January 17, 2020
Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
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1. Study Identification

Unique Protocol Identification Number
NCT03392896
Brief Title
Study of DCR-PHXC-101 in Normal Healthy Volunteers and Patients With Primary Hyperoxaluria
Official Title
A Placebo-Controlled, Single-Blind, Single-Center Phase 1 Study in Normal Healthy Volunteers and Open-Label Multi-Center Study in Patients With Primary Hyperoxaluria to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of DCR-PHXC Solution for Injection (Subcutaneous Use)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 6, 2017 (Actual)
Primary Completion Date
November 19, 2019 (Actual)
Study Completion Date
November 19, 2019 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a double-blind, placebo-controlled, dose escalation trial of DCR-PHXC in Healthy Volunteers (HVs) and patients with Primary Hyperoxaluria (PH). Once safety has been established in HV, PH patients with a confirmed diagnosis of PH1 and PH2 will be enrolled across multiple dosing cohorts. The study design will allow enrollment of PH patient cohorts at a given dose level once safety has been demonstrated in HV at that dose level. The study will be conducted in two parts: Part A: Single ascending dose (SAD) in HV; Part B: SAD in patients with PH1 and PH2 (lagging Part A by 1 dose level cohort).

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Two-arm (active and placebo), single-blind, SAD period (Group A, HVs) followed by open-label, SAD period (Group B, PH1 and PH2 patients).
Masking
ParticipantInvestigator
Masking Description
SAD period in HV is single-blind (unblinded clinical site staff member who is not a member of study team administers dose). SAD period in Group B (PH1 and PH2 patients) is open-label.
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A Active (DCR-PHXC)
Arm Type
Experimental
Arm Description
HVs, single ascending doses of DCR-PHXC.
Arm Title
Group A Placebo
Arm Type
Placebo Comparator
Arm Description
HVs, normal saline 0.9% injection to match active doses.
Arm Title
Group B Active (DCR-PHXC)
Arm Type
Experimental
Arm Description
PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.
Intervention Type
Drug
Intervention Name(s)
DCR-PHXC
Intervention Description
DCR-PHXC is a novel, potent, and long-acting small interference ribonucleic acid (siRNA) molecule conjugated to N-acteylgalactosamine (GalNAc) that is designed to decrease liver oxalate production. DCR-PHXC is delivered via subcutaneous (SC) injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single SC administration of placebo, which will be a sterile, preservative-free normal saline 0.9% solution for SC injection, which is of similar osmolality to the DCR-PHXC formulation.
Primary Outcome Measure Information:
Title
Number of patients with Treatment-Related Adverse Events (TEAEs)
Time Frame
Part A (SAD in HVs) screening through Day 29; Part B (SAD in PH patients) screening through Day 57

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Group A (HVs) Major Inclusion Criteria: Willing and able to provide informed consent and comply with study requirements. Male or female subjects between 18 and 55 years of age, inclusive. Subject must have a body mass index (BMI) 19.0 to 32 kg/m2, inclusive. Non-smokers, at least 1-month tobacco free, and willing to remain tobacco free through end of study (EOS). Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Group A (HVs) Major Exclusion Criteria: Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease. Routine or chronic use of more than 3 grams of acetaminophen (Tylenol) daily. History of kidney stones. Use of any investigational agent within 90 days before the first dose of study medication. History of donation of more than 450 mL of blood within 90 days prior to dosing in the clinical research center or planned donation less than 30 days after receiving Investigational Medicinal Product (IMP). Plasma or platelet donation within 7 days of dosing and through EOS. History of reactions to an oligonucleotide-based therapy. Males with female partners who are planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP. Plasma or platelet donation within 7 days of dosing and through EOS. Group B (PH1 and PH2 patients) Major Inclusion Criteria: Willing and able to provide informed consent and comply with study requirements. Male or female, at least 6 years of age. Minimum body weight of 25 kg. Genetic confirmation of PH1 and PH2 disease. Meet the 24 hour urine oxalate excretion requirements. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 4 weeks. Group B (PH1 and PH2 patients) Major Exclusion Criteria: Prior renal and/or hepatic transplantation. Currently receiving dialysis. Participation in any clinical study where they received an investigational agent within 4 months before enrollment. Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease. Liver function test (LFT) abnormalities. History of reactions to an oligonucleotide-based therapy.
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Centre d'Investigation Clinique - CIC 1407 - Hospices Civils de Lyon
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
University of Amsterdam
City
Amsterdam
ZIP/Postal Code
1012 WX
Country
Netherlands
Facility Name
Queen Elizabeth Hospital Birmingham
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
Birmingham Children's Hospital NHS Trust
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Wales
ZIP/Postal Code
CF484DR
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of DCR-PHXC-101 in Normal Healthy Volunteers and Patients With Primary Hyperoxaluria

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