Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT04580420
Previous Study | Return to List | Next Study

Safety & Efficacy of DCR-PHXC in Patients With PH1/2 and ESRD (PHYOX7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04580420
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Dicerna Pharmaceuticals, Inc.

Brief Summary:
The aim of this study is to evaluate DCR-PHXC in participants with PH1 or PH2 and severe renal impairment, with or without dialysis.

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Primary Hyperoxaluria Type 2 End Stage Renal Disease Drug: DCR-PHXC Phase 2

Detailed Description:

This is an open-label, repeat-dose, Phase 2 study of DCR-PHXC in participants with PH1 or PH2 and severe renal impairment, with or without dialysis.

Following the up-to-35- day screening period, participants will return to the clinic for monthly dosing visits through Day 180. Participants successfully completing the Day 180 visit will continue on to an extended follow-up period and receive open-label DCR-PHXC for an additional 3 years, or until DCR-PHXC is commercially available, whichever comes first. As participants in this extended treatment period will return to the clinic only every 3 months, participants and/or their caregivers will be trained in the at-home administration of DCR-PHXC.

The total duration of the study is approximately 2 years from first participant, first visit, to last participant, last Day 180 visit, with up to an additional 3 years of extended follow-up.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study to Evaluate the Safety and Efficacy of DCR-PHXC in Patients With Primary Hyperoxaluria Type 1 or 2 and Severe Renal Impairment, With or Without Dialysis
Actual Study Start Date : April 15, 2021
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : May 2025


Arm Intervention/treatment
Experimental: Open-Label DCR-PHXC
Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.
Drug: DCR-PHXC
Monthly dosing throughout study period
Other Name: Nedosiran




Primary Outcome Measures :
  1. Safety: Incidence of Events [ Time Frame: 180 days ]
    Characterize the safety of DCR-PHXC in participants with PH1 or PH2 and severe renal impairment, with or without dialysis.


Secondary Outcome Measures :
  1. Change from Baseline in Plasma Oxalate Concentration [ Time Frame: 180 Days ]
    To evaluate the effect of DCR-PHXC on Plasma Oxalate concentration from Baseline to day 180

  2. To characterize the PK of DCR PHXC in patients with PH by observing secondary parameters of the area under the curve. [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including secondary parameters of area under the curve (AUC)

  3. To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including maximum observed concentration (Cmax)

  4. To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including minimum observed concentration (Cmin)

  5. To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including time to maximum concentration (Tmax)

  6. To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including terminal elimination half-life (t1/2)

  7. Change in Frequency of Dialysis [ Time Frame: 180 days ]
    Change from Baseline in the frequency of dialysis over 180 days

  8. Change in Duration of Dialysis [ Time Frame: 180 days ]
    Change from Baseline in the duration of dialysis over 180 days


Other Outcome Measures:
  1. Change from Baseline in the Short Form (36) Health Survey (SF-36®) in adults [ Time Frame: 180 days ]

    To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.

    The SF 36 is a set of generic, coherent, and easily administered quality-of-life measures that taps 8 health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The 36 items are identical to the MOS SF 36 described in Ware and Sherbourne (1992). Participants respond to each item on a categorical scale. Categorical answers are transformed to a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state


  2. Change from Baseline in the EQ-5D-5L™ in adults [ Time Frame: 180 days ]

    To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.

    The EQ-5D-5L consists of the EQ 5D descriptive system and the EQ visual analogue scale (EQ VAS).

    The descriptive system has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the 5 dimensions can be combined into a 5-digit number that describes the participant's health state.

    The EQ VAS records the participant's self-rated health on a 20-cm vertical VAS, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine.' Participants are asked to place an "X" on the line that represents their health on that day.


  3. Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children [ Time Frame: 180 days ]

    To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.

    The 23-item PedsQL is comprised of 5 items in the Emotional, Social, and School Functioning dimensions (Psychosocial Health) and 8 items in the Physical Functioning (Physical Health) dimension. Items are reverse-scored on a 0 to 4 Likert scale and linearly transformed to a 0 to 100 scale, so that higher scores indicate better functioning and HRQOL. Scale Scores are the sum of the items in each dimension, divided by the number of items answered.


  4. Changes from Baseline number of kidney stones [ Time Frame: 180 days ]
    Evaluate the effect of DCR-PHXC on stone burden in participants with PH1 or PH2 and severe renal impairment through Kidney Ultrasound

  5. Changes from Baseline size of kidney stones [ Time Frame: 180 days ]
    Evaluate the effect of DCR-PHXC on stone burden in participants with PH1 or PH2 and severe renal impairment through Kidney Ultrasound



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Documented diagnosis of PH1 or PH2, confirmed by genotyping
  2. Estimated GFR at Screening <30mL/min normalized to 1.73m^2 BSA
  3. Plasma Oxalate >30μmol/L
  4. For participants receiving dialysis, total duration must be less than 18 months
  5. Male or Female

    1. Male participants:

      • A male participant with a female partner of childbearing potential must agree to use contraception during the treatment period and for at least 12 weeks after the last dose of study intervention and refrain from donating sperm during this period.
    2. Female participants:

      • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

      Not a woman of childbearing potential (WOCBP).

      • OR
      • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 12 weeks after the last dose of study intervention.
    3. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  6. Participant (and/or participant's parent or legal guardian if participant is a minor [defined as patient <18 years of age, or younger than the age of majority according to local regulations]) is capable of giving signed informed consent, which includes compliance with the requirement and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion Criteria:

  1. Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Prior renal transplantation is allowed.
  2. Documented evidence of severe systemic oxalosis, defined as overt signs of bone oxalate deposition in a plain x-ray of the left hand, as evidenced by large diffuse metaphyseal bands
  3. Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact patient safety
  4. Use of an RNAi drug, other DCR-PHXC, within the last 6 months
  5. History of reactions to an oligonucleotide-based therapy
  6. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months before Screening.
  7. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender
  8. Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody test at Screening
  9. Positive urine drug screen (to include at minimum: amphetamines, barbiturates, cocaine, opiates, and benzodiazepines). Urine drug screening is not required for participants ≤ 12 years of age. Exclusion for a positive screen is at the discretion of the Investigator.
  10. Known hypersensitivity to DCR-PHXC or any of its ingredients
  11. Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations

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): NCT04580420


Contacts
Layout table for location contacts
Contact: Medical Information 617-621-8097 medicalinfo@dicerna.com

Locations
Layout table for location information
United States, Minnesota
Clinical Trial Site Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trial Coordinator         
United States, New York
Clinical Trial Site Recruiting
New York, New York, United States, 10016
Contact: Clinical Trial Coordinator         
Spain
Clinical Trial Site Recruiting
Barcelona, Spain, 08035
Contact: Clinical Trial Coordinator         
Clinical Trial Site Recruiting
Santa Cruz De Tenerife, Spain, 38320
Contact: Clinical Trial Coordinator         
United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom, NWG 2Q3
Contact: Clinical Trial Coordinator         
Sponsors and Collaborators
Dicerna Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Chair: Alexandra Haagensen, MD, MBA Dicerna Pharmaceuticals, Inc.
Layout table for additonal information
Responsible Party: Dicerna Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04580420    
Other Study ID Numbers: DCR-PHXC-204
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dicerna Pharmaceuticals, Inc.:
PH1
PH2
ESRD
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Failure, Chronic
Hyperoxaluria, Primary
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Hyperoxaluria
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases