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

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ClinicalTrials.gov Identifier: NCT03392896
Recruitment Status : Active, not recruiting
First Posted : January 8, 2018
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Dicerna Pharmaceuticals, Inc.

Brief Summary:
This is a double-blind, placebo-controlled, dose escalation trial of DCR-PHXC in Normal Healthy Volunteers (NHVs) and patients with Primary Hyperoxaluria (PH). Once safety has been established in NHV, 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 NHV at that dose level. The study will be conducted in two parts: Part A: Single ascending dose (SAD) in NHV; Part B: SAD in patients with PH1 and PH2 (lagging Part A by 1 dose level cohort).

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Drug: DCR-PHXC Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two-arm (active and placebo), single-blind, SAD period (Group A, NHVs) followed by open-label, SAD period (Group B, PH1 and PH2 patients).
Masking: Double (Participant, Investigator)
Masking Description: SAD period in NHV 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.
Primary Purpose: Treatment
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)
Actual Study Start Date : December 6, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A Active (DCR-PHXC)
NHVs, single ascending doses of DCR-PHXC.
Drug: DCR-PHXC
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.

Placebo Comparator: Group A Placebo
NHVs, normal saline 0.9% injection to match active doses.
Drug: Placebo
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.

Experimental: Group B Active (DCR-PHXC)
PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.
Drug: DCR-PHXC
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.




Primary Outcome Measures :
  1. Number of patients with Treatment-Related Adverse Events (TEAEs) as assessed by CTCAE v4.03 [ Time Frame: Part A (SAD in NHVs) screening through Day 29; Part B (SAD in PH patients) screening through Day 57 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Group A (NHVs) 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 (NHVs) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03392896


Locations
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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
France
Centre d'Investigation Clinique - CIC 1407 - Hospices Civils de Lyon
Bron, France, 69677
Germany
Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie
Bonn, Germany, 53127
Netherlands
University of Amsterdam
Amsterdam, Netherlands, 1012 WX
United Kingdom
Queen Elizabeth Hospital Birmingham
Birmingham, United Kingdom, B15 2GW
Birmingham Children's Hospital NHS Trust
Birmingham, United Kingdom, B4 6NH
Clinical Trial Site
Wales, United Kingdom, CF484DR
Sponsors and Collaborators
Dicerna Pharmaceuticals, Inc.

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Responsible Party: Dicerna Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03392896     History of Changes
Other Study ID Numbers: DCR-PHXC-101
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Additional relevant MeSH terms:
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Hyperoxaluria, Primary
Hyperoxaluria
Kidney Diseases
Urologic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases