Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function

• Register: ClinicalTrials.gov
• Last refreshed on: 18 November 2024
• Main ID: NCT05001269
• Date of registration: 30/06/2021
• Prospective Registration: Yes
• Primary sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Public title: Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function PHYOX8
• Scientific title: A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 11Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function
• Date of first enrolment: February 22, 2022
• Target sample size: 25
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05001269
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, France, Germany, Italy, Japan, Lebanon, Morocco, Poland, Spain, Turkey, United Arab Emirates, United Kingdom, United States

Contacts

• Name: Medical Information

• Name: Sarb Shergill, PhD
• Affiliation: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Birth to 11 years of age inclusive, at the time of signing the informed consent.

2. Documented diagnosis of PH1 or PH2 or PH3 confirmed by genotyping (historically
available genotype information is acceptable for study eligibility).

3. 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 > 0.14 mol/mol in
participants from 5 to <7 years > 0.12 mol/mol in participants from 7 to 11
years

4. 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).

5. 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. Dose adjustments for
interval weight gain are acceptable.

6. Male or Female

Male participants:

A male participant with a female partner of childbearing potential must agree to use
contraception, as detailed in Section 10.5.2, 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.

Female participants:

A female participant is eligible to participate if she is not pregnant (see Section
10.5.1), not breastfeeding, and at least 1 of the following conditions applies:

Not a woman of childbearing potential (WOCBP) as defined in Section 10.5.1 OR A
WOCBP who agrees to follow the contraceptive guidance in Section 10.5.2 during the
treatment period and for at least 12 weeks after the last dose of study
intervention.

Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.

Note: If the childbearing potential changes after start of the study (e.g., a
premenarchal female participant experiences menarche) or the risk of pregnancy
changes (e.g., a female participant who is not heterosexually active becomes
active), the participant must discuss this with the Investigator, who should
determine if a female participant must begin a highly effective method of
contraception or a male participant must use a condom. If reproductive status is
questionable, additional evaluation should be considered.

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.

a. For children younger than 12 years of age, assent will be based on local
regulation. If assent is required, participant must be able to provide written
assent for participation.

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 detailed in Section 5.3.


Age minimum: N/A
Age maximum: 11 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Hyperoxaluria Type 2

Primary Hyperoxaluria Type 1

Primary Hyperoxaluria

Primary Hyperoxaluria Type 3

Intervention(s)

Drug: nedosiran

Primary Outcome(s)

Efficacy: Percent change in urinary oxalate to creatinine ratio [Time Frame: 180 days]

Efficacy: Absolute change in urinary oxalate to creatinine ratio [Time Frame: 180 days]

Secondary Outcome(s)

To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin). [Time Frame: 180 days]

Safety: Changes from baseline in ECG: PR interval [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Coagulation [Time Frame: 180 days]

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]

Safety: Changes from baseline in ECG: QRS duration [Time Frame: 180 days]

Safety: Changes from baseline in ECG: Rhythm [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Urine Oxalate [Time Frame: 180 days]

Safety: Incidence of Events [Time Frame: 180 days]

Safety: Changes from baseline in ECG: Ventricular Rate [Time Frame: 180 days]

To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax). [Time Frame: 180 days]

Safety: Changes from baseline in Vitals: blood pressure [Time Frame: 180 days]

Safety: Changes from baseline in Vitals: pulse rate [Time Frame: 180 days]

Safety: Changes from baseline in Vitals: respiratory rate [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Plasma Oxalate [Time Frame: 180 days]

Safety: Changes from baseline in Vitals: temperature [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Antibody [Time Frame: 180 days]

Efficacy: eGFR changes [Time Frame: 180 days]

Safety: Changes from baseline in ECG: QT interval [Time Frame: 180 days]

To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax). [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Clinical Chemistry [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Hematology [Time Frame: 180 days]

Safety: Changes from baseline: Labs - Urinalysis [Time Frame: 180 days]

Safety: Changes from baseline: Physical Exam [Time Frame: 180 days]

To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2). [Time Frame: 180 days]

Secondary ID(s)

DCR-PHXC-203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors