E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Primary Hyperoxaluria is where the liver overproduces oxalate. As a result calcium-oxalate crystals form in the urinary system and lead to the formation of kidney stones and impaired kidney function. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020703 |
E.1.2 | Term | Hyperoxaluria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of nedosiran in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the safety of nedosiran in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine 2. To characterize the PK of nedosiran in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine 3. To assess the efficacy of nedosiran in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine 4. To evaluate the effect of nedosiran on eGFR in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Estimated glomerular filtration rate (eGFR) at Screening ≥ 30 mL/min normalized to 1.73 m2 body surface area (BSA). 2. Average spot Uox-to-creatinine ratio at Screening above 2 times the 95th percentile for age based on 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 < 5 years > 0.14 mol/mol in participants from 5 to < 7 years > 0.12 mol/mol in participants from 7 to 11 years
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E.4 | Principal exclusion criteria |
1. Renal or hepatic transplantation (prior or planned within the study period) 2. Plasma oxalate (Pox) > 30 µmol/L at Screening 3.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)
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent and absolute change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 participant subgroups
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The percent and absolute change in average spot urinary oxalate-to creatinine ratio from Baseline to Day 180 will be summarized |
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E.5.2 | Secondary end point(s) |
1. The incidence and nature of TEAEs and SAEs Change from Baseline in 12-lead ECG, physical examination findings, vital sign assessments, and clinical laboratory tests 2. Plasma PK parameters for nedosiran and/or its metabolites, including Cmax, AUCt and AUC∞ (if estimable) 3. Percentage of participants with spot urinary oxalate-to-creatinine ratio ≤ the ULN or ≤ 1.5 x ULN at any time point through Month 6 in PH1, PH2, or PH3 participant subgroups 4. Change from Baseline in eGFR at Month 6 (only in participants ≥ 12 Months of age at Screening) in PH1, PH2, or PH3 participant subgroups |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Descriptive statistics will be provided for absolute values and changes from baseline in physical examination findings, vital sign measurements,ECGs, and clinical laboratory results at each timepoint 2. Pharmacokinetic analyses will be described in the SAP finalized before database lock. The population PK analysis will be presented separately from the main CSR 3. The percentage of participants with spot urinary oxalate-to-creatinine ratio ≤ the ULN and ≤ 1.5 x ULN at any time point through Month 6 will be summarized. 4. The percent change from baseline in eGFR at Month 6 (only in participants ≥ 12 Months of age at Screening) will be summarized. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Japan |
Lebanon |
Morocco |
United States |
France |
Poland |
Spain |
Germany |
Italy |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A participant is considered to have completed the study if he or she has completed all phases of the study, including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), Section 1.3. The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial globally. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |