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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.

Tracking Information
First Submitted Date  ICMJE December 21, 2017
First Posted Date  ICMJE January 8, 2018
Last Update Posted Date February 18, 2019
Actual Study Start Date  ICMJE December 6, 2017
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03392896 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of DCR-PHXC-101 in Normal Healthy Volunteers and Patients With Primary Hyperoxaluria
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Primary Hyperoxaluria
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: Group A Active (DCR-PHXC)
    NHVs, single ascending doses of DCR-PHXC.
    Intervention: Drug: DCR-PHXC
  • Placebo Comparator: Group A Placebo
    NHVs, normal saline 0.9% injection to match active doses.
    Intervention: Drug: Placebo
  • Experimental: Group B Active (DCR-PHXC)
    PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.
    Intervention: Drug: DCR-PHXC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 2, 2018)
41
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 55 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03392896
Other Study ID Numbers  ICMJE DCR-PHXC-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dicerna Pharmaceuticals, Inc.
Study Sponsor  ICMJE Dicerna Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Dicerna Pharmaceuticals, Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP