Nedosiran in Pediatric Patients From Birth to 5 Years of Age With PH and Relatively Intact Renal Function

Brief Title

Nedosiran in Pediatric Patients From Birth to 5 Years of Age With PH and Relatively Intact Renal Function

Official Title

A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 5 Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function

Brief Summary

      The aim of this study is to evaluate nedosiran in participants 5 years of age and younger who
      have Primary Hyperoxaluria with relatively intact renal function.
    

Detailed Description

      This is an open-label, repeat-dose, Phase 2 study of nedosiran in participants 5 years of age
      or younger who have PH with relatively intact renal function.

      Following the up-to-35- day screening period, participants will return to the clinic for
      monthly dosing visits through Day 180.

      The total duration of this study is approximately 15 months from first participant, first
      visit, until last participant, last visit.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Efficacy: Percent change in urinary oxalate to creatinine ratio

Secondary Outcome

 Safety: Incidence of Events

Condition

Primary Hyperoxaluria

Intervention

nedosiran

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

10

Start Date

October 2021

Completion Date

December 2022

Primary Completion Date

October 2022

Eligibility Criteria

        Inclusion Criteria:

          1. Documented diagnosis of PH1 or PH2 confirmed by genotyping (historically available
             genotype information is acceptable for study eligibility).

          2. Average spot Uox to creatinine ratio at Screening above 2 times the 95th percentile
             for age (Matos et al, 1999):

               -  > 0.44 mol/mol in participants < 6 months

               -  > 0.34 mol/mol in participants from 6 months to < 12 months

               -  > 0.26 mol/mol in participants 12 months to < 2 years

               -  > 0.20 mol/mol in participants from 2 to < 3 years and

               -  > 0.16 mol/mol in participants from 3 to 5 years

          3. Estimated GFR at Screening ≥ 30 mL/min normalized to 1.73 m2 BSA. See Section 8.2.6.1
             for equations. For infants aged less than 12 months, serum creatinine below the 97th
             percentile of a healthy population (Boer et al., 2010).

          4. Participants must have been on a stable treatment regimen for PH for 3 months prior to
             Day 1 and parent(s)/legal guardian should be willing to ensure participant remains on
             the same stable treatment regimen during the study.

          5. Body weight >10 kg

          6. Male or Female

          7. Participant's parent or legal guardian is capable of giving signed informed consent,
             which includes compliance with the requirements and restrictions listed in the ICF and
             in this protocol.

          8. A legal guardian or primary caregiver must be available to help the study-site
             personnel ensure follow up; accompany the participant to the study site on each
             assessment day according to the SoA (e.g., able to comply with scheduled visits,
             treatment plan, laboratory tests and other study procedures); consistently and
             consecutively be available to provide information on the participant using the rating
             scales during the scheduled study visits; accurately and reliably dispense study
             intervention as directed.

          9. Affiliated with or is a beneficiary of a health insurance system (if applicable per
             national regulations)

        Exclusion Criteria:

          1. Prior renal or hepatic transplantation; or planned transplantation within the study
             period

          2. Currently receiving dialysis or anticipating requirement for dialysis during the study
             period

          3. Plasma oxalate (Pox) > 30 μmol/L at Screening

          4. Documented evidence of clinical manifestations of severe systemic oxalosis (including
             preexisting retinal, heart, or skin calcifications, or history of severe bone pain,
             pathological fractures, or bone deformations)

          5. Presence of any condition or comorbidities that would interfere with study compliance
             or data interpretation or potentially impact participant's safety including, but not
             restricted to:

               1. Severe intercurrent illness

               2. Known causes of active liver disease/injury or transaminase elevation (e.g.,
                  alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis
                  [NAFLD/NASH])

               3. History of serious mental illness that includes, but is not limited to,
                  schizophrenia, bipolar disorder, or severe depression requiring hospitalization
                  or pharmacological intervention

               4. Clinically relevant history or presence of cardiovascular, respiratory,
                  gastrointestinal, hematological, lymphatic, neurological, musculoskeletal,
                  genitourinary, immunological diseases, including dermatological including rash,
                  severe eczema or dermatitis, or connective tissue diseases or disorders

          6. Use of an RNAi drug within the last 6 months

          7. History of 1 or more of the following reactions to an oligonucleotide-based therapy:

               1. Severe thrombocytopenia (platelet count ≤ 100,000/μL)

               2. Hepatotoxicity, defined as ALT or AST > 3 times the upper ULN and total bilirubin
                  > 2 × ULN or INR > 1.5

               3. Severe flu-like symptoms leading to discontinuation of therapy

               4. Localized skin reaction from the injection (graded severe) leading to
                  discontinuation of therapy

               5. Coagulopathy/clinically significant prolongation of clotting time

          8. Participation in any clinical study in which they received an IMP within 4 months or 5
             times the half-life of the drug (whichever is longer) before Screening

             a. For IMPs with the potential to reduce urine and/or plasma oxalate concentrations,
             these concentrations must have returned to historical baseline levels prior to
             Screening

          9. Liver function test (LFT) abnormalities: ALT and/or AST > 1.5 × ULN for age and gender

         10. Known hypersensitivity to nedosiran, 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 - 5 Years

Accepts Healthy Volunteers

No

Contacts

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



Administrative Informations


NCT ID

NCT05001269

Organization ID

DCR-PHXC-203


Responsible Party

Sponsor

Study Sponsor

Dicerna Pharmaceuticals, Inc.


Study Sponsor

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


Verification Date

September 2021