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

Brief Title

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

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

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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Safety: Incidence of Events

Secondary Outcome

 Change from Baseline in Plasma Oxalate Concentration

Condition

Primary Hyperoxaluria

Intervention

DCR-PHXC

Study Arms / Comparison Groups

 Open-Label DCR-PHXC
Description:  Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

April 15, 2021

Completion Date

May 2025

Primary Completion Date

November 2022

Eligibility 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
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Alexandra Haagensen, MD, MBA, 617-621-8097, [email protected]

Location Countries

Spain

Location Countries

Spain

Administrative Informations


NCT ID

NCT04580420

Organization ID

DCR-PHXC-204


Responsible Party

Sponsor

Study Sponsor

Dicerna Pharmaceuticals, Inc.


Study Sponsor

Alexandra Haagensen, MD, MBA, Study Chair, Dicerna Pharmaceuticals, Inc.


Verification Date

July 2021