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Clinical Trial Results:
A Phase 2 Open-Label Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Nedosiran in Pediatric Patients from Birth to 11 Years of Age with Primary Hyperoxaluria and Relatively Intact Renal Function

Summary
EudraCT number	2021-001083-16
Trial protocol	DE ES PL IT
Global end of trial date	05 Feb 2025

Results information
Results version number	v1(current)
This version publication date	22 Aug 2025
First version publication date	22 Aug 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

DCR-PHXC-203

ISRCTN number

US NCT number

NCT05001269

WHO universal trial number (UTN)

Sponsor organisation name

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Sponsor organisation address

Novo Nordisk, Novo Allé, Bagsvaerd, Denmark, 2880

Public contact

Clinical Reporting Office (2834), Dicerna Pharmaceuticals, Inc., a Novo Nordisk company, clinicaltrials@novonordisk.com

Scientific contact

Clinical Reporting Office (2834), Dicerna Pharmaceuticals, Inc., a Novo Nordisk company, clinicaltrials@novonordisk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002493-PIP01-18

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

15 May 2025

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Feb 2025

Was the trial ended prematurely?

Main objective of the trial

Main objective of the study trial is to assess the efficacy of nedosiran in neonates, infants, and children with PH and relatively intact renal function based upon eGFR and serum creatinine

Protection of trial subjects

This study will be conducted in accordance with the protocol and with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and CIOMS International Ethical Guidelines (CIOMS VI, 2005); applicable International Conference on Harmonisation (ICH) Good Clinical practices (GCP) guidelines, and applicable laws and regulations, including privacy laws. With regard to paediatric participants, the ICH Harmonised Tripartite Guideline: Clinical Investigation of Medicinal Products in the Paediatric Population (E11, 20 July 2000) and the European Commission Ethical Considerations for Clinical Trials on Medicinal Products Conducted with Minors (18 September 2017) were considered during the design of the trial, and blood volume minimized where possible.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Feb 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 5

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

Japan: 1

Country: Number of subjects enrolled

Lebanon: 9

Country: Number of subjects enrolled

Türkiye: 3

Country: Number of subjects enrolled

United Arab Emirates: 2

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 13 sites in 9 countries.

Screening details

This is Phase 2, open-label, single-arm uncontrolled study in paediatric subjects with genetically confirmed primary hyperoxaluria (PH), with relatively intact renal function based upon estimated glomerular filtration rate (eGFR) and serum creatinine. A total of 27 subjects were enrolled in the study and all of them completed the study.

Period 1 title

Overall Period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Children 0 to <2 years

Arm description

All subjects that included neonates (0 to less than [<] 2 years) with primary hyperoxaluria (PH) and relatively intact renal function based upon eGFR and serum creatinine, received monthly dose of nedosiran (3.5 milligrams per kilogram [mg/kg], not to exceed 170 milligrams [mg]), subcutaneously from Day 1 though Month 6.

Arm type

Experimental

Investigational medicinal product name

Nedosiran

Investigational medicinal product code

DCR-PHXC

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Subcutaneous use

Dosage and administration details

Subject were administered a sterile formulation of drug substance (nedosiran sodium) in water for injection, intended for subcutaneous administration. Total monthly dose (3.5 mg/kg, not to exceed 170 mg) was calculated based upon body weight on Day 1 of the study that remained constant throughout the study.

Children 2 to <6 years

Arm description

All subjects that included infants (2 to <6 years) with PH and relatively intact renal function based upon eGFR and serum creatinine, received monthly dose of nedosiran (3.5 mg/kg, not to exceed 170 mg), subcutaneously from Day 1 though Month 6.

Arm type

Experimental

Investigational medicinal product name

Nedosiran

Investigational medicinal product code

DCR-PHXC

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Subcutaneous use

Dosage and administration details

Children 6 to 11 years

Arm description

All subjects that included children (6 to 11 years) with PH and relatively intact renal function based upon eGFR and serum creatinine, received monthly dose of nedosiran (3.5 mg/kg, not to exceed 170 mg), subcutaneously from Day 1 though Month 6.

Arm type

Experimental

Investigational medicinal product name

Nedosiran

Investigational medicinal product code

DCR-PHXC

Other name

Pharmaceutical forms

Sterile concentrate

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Started	5	13	9
Modified Intent-To-Treat (MITT)	3 ^[1]	9 ^[2]	8 ^[3]
‌Safety	5	13	9
Completed	5	13	9

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This milestone reports MITT population with 3 subjects reported under 0 to <2 years age group.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This milestone reports MITT population with 9 subjects reported under 2 to <6 years age group.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This milestone reports MITT population with 3 subjects reported under 6 to 11 years age group.

Baseline characteristics

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Reporting group title

Children 0 to <2 years

Reporting group description

Reporting group title

Children 2 to <6 years

Reporting group description

Reporting group title

Children 6 to 11 years

Reporting group description

Reporting group values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years	Total
Number of subjects	5	13	9	27
Age Categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	5	0	0	5
Children (2-11 years)	0	13	9	22
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	1.30 ( 0.529 )	3.54 ( 1.198 )	7.78 ( 1.093 )	-
Gender Categorical
Units: Subjects
Female	1	6	4	11
Male	4	7	5	16

End points

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Reporting group title

Children 0 to <2 years

Reporting group description

Reporting group title

Children 2 to <6 years

Reporting group description

Reporting group title

Children 6 to 11 years

Reporting group description

Primary: Percent change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

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End point title

Percent change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups ^[1]

End point description

This endpoint reported percent change from baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in paediatric subjects (birth to 11 years of age) with genetically confirmed primary hyperoxaluria type 1 (PH1), primary hyperoxaluria type 2 (PH2), or primary hyperoxaluria type 3 (PH3) subgroups. The MITT Population included all subjects who received at least 1 dose of study intervention and have at least 1 post-baseline spot urinary oxalate to creatinine ratio. Here 'Number of subject analysed' signified 'Overall number of subjects analysed' and 'n' signified 'Number Analysed' that is number of subjects with available data for particular timepoint, for the respective arms; and "99999" signifies that data for these categories were not evaluable as the number of subject for the respective category was 0.

End point type

Primary

End point timeframe

Baseline (Week 0), Month 6

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypotheses confirmatory testing was planned in this study. The endpoint is descriptive in nature.

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Percent change
arithmetic mean (standard deviation)
PH1 (n=3,9,8)	-74.06 ( 13.193 )	-68.34 ( 8.574 )	-61.44 ( 24.565 )
PH2 (n=0,4,1)	99999 ( 99999 )	-17.98 ( 37.847 )	-16.10 ( 0 )
PH3 (n=2,0,0)	-41.43 ( 13.633 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Primary: Absolute change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

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End point title

Absolute change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups ^[2]

End point description

This endpoint reported absolute change from baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in paediatric subjects (birth to 11 years of age) with genetically confirmed PH1, PH2, or PH3 subgroups. The MITT Population included all subjects who received at least 1 dose of study intervention and have at least 1 post-baseline spot urinary oxalate to creatinine ratio. Here 'Number of subject analysed' signified 'Overall number of subjects analysed' and 'n' signified 'Number Analysed' that is number of subjects with available data for particular timepoint, for the respective arms; and "99999" signifies that data for these categories were not evaluable as the number of subject for the respective category was 0.

End point type

Primary

End point timeframe

Baseline (Week 0), Month 6

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypotheses confirmatory testing was planned in this study. The endpoint is descriptive in nature.

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: micromole/millimole
arithmetic mean (standard deviation)
PH1 (n=3,9,8)	-563.972 ( 378.3308 )	-316.344 ( 150.6332 )	-189.106 ( 120.5939 )
PH2 (n=0,4,1)	99999 ( 99999 )	-64.458 ( 92.5196 )	-27.583 ( 0 )
PH3 (n=2,0,0)	-135.283 ( 17.1591 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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End point title

Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

End point description

This endpoint reported number of incidents of TEAEs and SAEs. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, and medical events. An AE will be defined as treatment emergent if they have an onset or worsen in severity after a subject receives the study intervention. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

From baseline (Week 0) up to Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Events
TEAEs	37	66	38
SAEs	1	4	2

No statistical analyses for this end point

Secondary: Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature

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End point title

Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature

End point description

This endpoint reported nature of TEAEs and SAEs. An AE is any untoward medical occurrence in clinical study subject, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent disability/incapacity, is a congenital anomaly/birth defect, and medical events. An AE is treatment emergent if they have an onset or worsen in severity after a subject receives the study drug. TEAEs are considered as leading to discontinuation if the action taken is marked as “drug withdrawn” on the case report form. TEAEs of special interest include injection site reactions, muscle pain and weakness, and kidney stone events. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

From baseline (Week 0) up to Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Events
Treatment Related TEAE	2	7	4
TEAE Leading to Treatment Interruption	1	0	0
TEAE Leading to Treatment Discontinuation	0	0	0
Serious Treatment Related TEAE	0	0	0
Fatal TEAE	0	0	0
TEAE of Special Interest	7	8	8

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead ECG- RR Interval

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End point title

Change from Baseline in 12-lead ECG- RR Interval

End point description

This endpoint reported change from baseline to Month 6 in RR Interval. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: seconds
arithmetic mean (standard deviation)	0.1 ( 0.16 )	0.0 ( 0.10 )	-0.1 ( 0.12 )

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate

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End point title

Change from Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate

End point description

This endpoint reported change from baseline to Month 6 in ECG mean heart rate. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: beats/minute
arithmetic mean (standard deviation)	-11.6 ( 32.34 )	-4.2 ( 15.73 )	6.2 ( 16.98 )

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead ECG-QTcF Interval, Aggregate

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End point title

Change from Baseline in 12-lead ECG-QTcF Interval, Aggregate

End point description

This endpoint reported change from baseline to Month 6 in aggregate QTcF Interval. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: milliseconds
arithmetic mean (standard deviation)	21.0 ( 17.68 )	4.5 ( 14.88 )	1.8 ( 13.29 )

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead ECG-QT Interval, Aggregate

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End point title

Change from Baseline in 12-lead ECG-QT Interval, Aggregate

End point description

This endpoint reported change from baseline to Month 6 in aggregate QT Interval. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: milliseconds
arithmetic mean (standard deviation)	28.0 ( 30.60 )	8.2 ( 20.46 )	-6.7 ( 23.69 )

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead ECG-QRS Duration, Aggregate

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End point title

Change from Baseline in 12-lead ECG-QRS Duration, Aggregate

End point description

This endpoint reported change from baseline to Month 6 in aggregate QRS Interval. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: milliseconds
arithmetic mean (standard deviation)	3.2 ( 5.45 )	0.5 ( 6.44 )	1.7 ( 3.24 )

No statistical analyses for this end point

Secondary: Change from Baseline in 12-lead ECG-PR Interval, Aggregate

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End point title

Change from Baseline in 12-lead ECG-PR Interval, Aggregate

End point description

This endpoint reported change from baseline to Month 6 in aggregate PR Interval. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: milliseconds
arithmetic mean (standard deviation)	3.6 ( 8.56 )	1.8 ( 6.39 )	-1.0 ( 8.75 )

No statistical analyses for this end point

Secondary: Change from Baseline in Subjects with Significant Findings- Physical Examination

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End point title

Change from Baseline in Subjects with Significant Findings- Physical Examination

End point description

This endpoint reported change from baseline to Month 6 in number of subjects with significant findings (physical examination). Change from baseline was calculated using formula: value at current time point – baseline value. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: subjects
number (not applicable)	0	0	-1

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Body Mass Index

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End point title

Change from Baseline in vital sign assessment-Body Mass Index

End point description

This endpoint reported change from baseline to Month 6 in subject's BMI. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Kilograms per metre square (kg/m^2)
arithmetic mean (standard deviation)	-0.668 ( 0.8318 )	0.152 ( 0.9265 )	0.608 ( 0.9316 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Weight

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End point title

Change from Baseline in vital sign assessment-Weight

End point description

This endpoint reported change from baseline to Month 6 in subject's weights. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: kilograms (kg)
arithmetic mean (standard deviation)	1.130 ( 0.3033 )	1.488 ( 1.2636 )	2.411 ( 1.4575 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment- Height

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End point title

Change from Baseline in vital sign assessment- Height

End point description

This endpoint reported change from baseline to Month 6 in subject's heights. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: centimetres
arithmetic mean (standard deviation)	6.24 ( 2.220 )	4.01 ( 1.237 )	2.76 ( 1.548 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Oral Body Temperature

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End point title

Change from Baseline in vital sign assessment-Oral Body Temperature

End point description

This endpoint reported change from baseline to Month 6 in subject's oral body temperature. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: degree celcius (˚C)
arithmetic mean (standard deviation)	0.36 ( 0.555 )	-0.01 ( 0.441 )	-0.00 ( 0.339 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Respiratory Rate

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End point title

Change from Baseline in vital sign assessment-Respiratory Rate

End point description

This endpoint reported change from baseline to Month 6 in subject's respiratory rate. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: breaths/minute
arithmetic mean (standard deviation)	-1.4 ( 6.77 )	-1.8 ( 4.17 )	0.8 ( 2.44 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Heart Rate

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End point title

Change from Baseline in vital sign assessment-Heart Rate

End point description

This endpoint reported change from baseline to Month 6 in subject's heart rate. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: beats/minute
arithmetic mean (standard deviation)	6.2 ( 14.13 )	-1.5 ( 12.52 )	4.7 ( 16.96 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Haemoglobin

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End point title

Change from Baseline in Haematology assessment: Haemoglobin

End point description

This endpoint reported change from baseline to Month 6 in subject's haemoglobin. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Grams per decilitre (g/dL)
arithmetic mean (standard deviation)	0.575 ( 0.7632 )	0.155 ( 0.8092 )	0.250 ( 0.7051 )

No statistical analyses for this end point

Secondary: Change from Baseline in vital sign assessment-Systolic Blood Pressure and Diastolic Blood Pressure

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End point title

Change from Baseline in vital sign assessment-Systolic Blood Pressure and Diastolic Blood Pressure

End point description

This endpoint reported change from baseline to Month 6 in subject's systolic and diastolic blood pressure. Safety population included all subjects who received at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Millimetres of Mercury (mmHg)
arithmetic mean (standard deviation)
Systolic Blood Pressure	6.8 ( 22.20 )	-6.8 ( 17.21 )	2.8 ( 7.95 )
Diastolic Blood Pressure	7.6 ( 17.84 )	1.1 ( 13.62 )	2.8 ( 4.27 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Erythrocytes

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End point title

Change from Baseline in Haematology assessment: Erythrocytes

End point description

This endpoint reported change from baseline to Month 6 in subject's erythrocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Tera cells per litre (10^12 cells /L)
arithmetic mean (standard deviation)	0.195 ( 0.3375 )	0.173 ( 0.2765 )	0.055 ( 0.2076 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Haematocrit

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End point title

Change from Baseline in Haematology assessment: Haematocrit

End point description

This endpoint reported change from baseline to Month 6 in subject's haematocrit. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Haematocrit
arithmetic mean (standard deviation)	0.01 ( 0.025 )	0.01 ( 0.019 )	0.00 ( 0.023 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Volume

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End point title

Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Volume

End point description

This endpoint reported change from baseline to Month 6 in subject's erythrocytes mean corpuscular volume. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Femtolitre (fL)
arithmetic mean (standard deviation)	1.70 ( 3.818 )	-1.25 ( 2.393 )	-0.05 ( 2.530 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Haemoglobin

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End point title

Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Haemoglobin

End point description

This endpoint reported change from baseline to Month 6 in subject's erythrocytes mean corpuscular haemoglobin. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: picograms
arithmetic mean (standard deviation)	0.25 ( 0.624 )	-0.48 ( 1.244 )	0.18 ( 0.738 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology Assessment: Erythrocytes Mean Corpuscular Haemoglobin Concentration

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End point title

Change from Baseline in Haematology Assessment: Erythrocytes Mean Corpuscular Haemoglobin Concentration

End point description

This endpoint reported change from baseline to Month 6 in subject's erythrocytes mean corpuscular heamoglobin concentration. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: g/dL
arithmetic mean (standard deviation)	-0.42 ( 1.754 )	-0.09 ( 1.691 )	0.19 ( 0.783 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Reticulocytes

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End point title

Change from Baseline in Haematology assessment: Reticulocytes

End point description

This endpoint reported change from baseline to Month 6 in subject's reticulocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Percentage of Reticulocytes
arithmetic mean (standard deviation)	0.15 ( 0.208 )	0.14 ( 0.781 )	-0.08 ( 0.443 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Platelets

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End point title

Change from Baseline in Haematology assessment: Platelets

End point description

This endpoint reported change from baseline to Month 6 in subject's platelets. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	7
Units: Giga cells per litre (10^9 cells /L)
arithmetic mean (standard deviation)	-1.8 ( 40.87 )	-18.6 ( 62.25 )	-27.7 ( 102.53 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Leukocytes

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End point title

Change from Baseline in Haematology assessment: Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in subject's leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	-1.460 ( 2.1985 )	0.383 ( 2.3556 )	-0.625 ( 2.2732 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Lymphocytes

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End point title

Change from Baseline in Haematology assessment: Lymphocytes

End point description

This endpoint reported change from baseline to Month 6 in subject's lymphocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	-1.808 ( 2.3547 )	0.429 ( 1.1896 )	-0.577 ( 0.9109 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Monocytes

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End point title

Change from Baseline in Haematology assessment: Monocytes

End point description

This endpoint reported change from baseline to Month 6 in subject's monocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	-0.013 ( 0.2295 )	-0.024 ( 0.1306 )	-0.038 ( 0.1288 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Mean Platelet Volume

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End point title

Change from Baseline in Haematology assessment: Mean Platelet Volume

End point description

This endpoint reported change from baseline to Month 6 in subject's mean platelet volume. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	7
Units: fL
arithmetic mean (standard deviation)	0.05 ( 0.507 )	-0.10 ( 0.610 )	0.03 ( 0.553 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Basophils

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End point title

Change from Baseline in Haematology assessment: Basophils

End point description

This endpoint reported change from baseline to Month 6 in subject's basophils. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	0.035 ( 0.0545 )	-0.008 ( 0.0606 )	-0.014 ( 0.0320 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Eosinophils

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End point title

Change from Baseline in Haematology assessment: Eosinophils

End point description

This endpoint reported change from baseline to Month 6 in subject's eosinophils. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	0.078 ( 0.1441 )	0.029 ( 0.1495 )	0.106 ( 0.3064 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Neutrophils

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End point title

Change from Baseline in Haematology assessment: Neutrophils

End point description

This endpoint reported change from baseline to Month 6 in subject's neutrophils. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: 10^9 cells /L
arithmetic mean (standard deviation)	-0.165 ( 2.1021 )	-0.073 ( 1.4642 )	-0.106 ( 1.3720 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Eosinophils/Leukocytes

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End point title

Change from Baseline in Haematology assessment: Eosinophils/Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in the ratio of eosinophils/leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Eosinophils/Leukocytes
arithmetic mean (standard deviation)	1.33 ( 1.531 )	0.22 ( 1.829 )	1.29 ( 3.061 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Monocytes/Leukocytes

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End point title

Change from Baseline in Haematology assessment: Monocytes/Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in the ratio of monocytes/leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Lymphocytes/Leukocytes
arithmetic mean (standard deviation)	0.70 ( 2.534 )	-0.45 ( 1.109 )	-0.14 ( 1.255 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Lymphocytes/Leukocytes

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End point title

Change from Baseline in Haematology assessment: Lymphocytes/Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in the ratio of lymphocytes/leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Lymphocytes/Leukocytes
arithmetic mean (standard deviation)	-10.25 ( 16.801 )	2.20 ( 9.901 )	-2.51 ( 13.862 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Neutrophils/Leukocytes

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End point title

Change from Baseline in Haematology assessment: Neutrophils/Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in the ratio of neutrophils/leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Neutrophils/Leukocytes
arithmetic mean (standard deviation)	7.63 ( 14.717 )	-2.31 ( 9.655 )	1.50 ( 12.398 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase

End point description

This endpoint reported change from baseline to Month 6 in alanine aminotransferase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: Units per litre (U/L)
arithmetic mean (standard deviation)	-1.8 ( 4.44 )	14.9 ( 24.68 )	5.1 ( 4.61 )

No statistical analyses for this end point

Secondary: Change from Baseline in Haematology assessment: Basophils/Leukocytes

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End point title

Change from Baseline in Haematology assessment: Basophils/Leukocytes

End point description

This endpoint reported change from baseline to Month 6 in the ratio of basophils/leukocytes. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	11	8
Units: Ratio of Basophils/Leukocytes
arithmetic mean (standard deviation)	0.55 ( 0.777 )	-0.01 ( 0.517 )	-0.09 ( 0.606 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase

End point description

This endpoint reported change from baseline to Month 6 in aspartate aminotransferase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: U/L
arithmetic mean (standard deviation)	-4.0 ( 11.94 )	6.4 ( 13.83 )	7.1 ( 6.94 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase

End point description

This endpoint reported change from baseline to Month 6 in lactate dehydrogenase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	4	12	7
Units: U/L
arithmetic mean (standard deviation)	-29.3 ( 17.29 )	19.5 ( 67.20 )	1.6 ( 23.44 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Glutamate Dehydrogenase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Glutamate Dehydrogenase

End point description

This endpoint reported change from baseline to Month 6 in glutamate dehydrogenase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	12	8
Units: U/L
arithmetic mean (standard deviation)	0.00 ( 0.000 )	0.28 ( 0.601 )	0.06 ( 0.316 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Gamma Glutamyl Transferase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Gamma Glutamyl Transferase

End point description

This endpoint reported change from baseline to Month 6 in gamma glutamyl transferase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: U/L
arithmetic mean (standard deviation)	-0.4 ( 4.45 )	1.4 ( 1.89 )	1.6 ( 0.92 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase

End point description

This endpoint reported change from baseline to Month 6 in alkaline phosphatase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: U/L
arithmetic mean (standard deviation)	-6.6 ( 19.65 )	14.6 ( 37.61 )	-8.4 ( 14.88 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Bilirubin and Direct Bilirubin

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End point title

Change from Baseline in Clinical Chemistry Parameter: Bilirubin and Direct Bilirubin

End point description

This endpoint reported change from baseline to Month 6 in bilirubin and direct bilirubin. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subject analysed' signified 'Overall number of subjects analysed' and 'n' signified 'Number Analyzed' that is number of subjects with available data for particular timepoint, for the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: micromole per litre (umol/L)
arithmetic mean (standard deviation)
Bilirubin (n=5,13,8)	-0.46 ( 1.389 )	1.62 ( 3.467 )	1.23 ( 2.355 )
Direct Bilirubin (n=4,12,7)	-0.07 ( 0.096 )	0.20 ( 1.224 )	-0.03 ( 0.588 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Protein

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End point title

Change from Baseline in Clinical Chemistry Parameter: Protein

End point description

This endpoint reported change from baseline to Month 6 in protein. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: Grams per litre (g/L)
arithmetic mean (standard deviation)	-0.8 ( 6.76 )	0.6 ( 3.71 )	-2.0 ( 5.55 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Albumin

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End point title

Change from Baseline in Clinical Chemistry Parameter: Albumin

End point description

This endpoint reported change from baseline to Month 6 in albumin. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: g/L
arithmetic mean (standard deviation)	-0.2 ( 2.17 )	1.2 ( 2.79 )	-0.2 ( 2.64 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Creatine Kinase

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End point title

Change from Baseline in Clinical Chemistry Parameter: Creatine Kinase

End point description

This endpoint reported change from baseline to Month 6 in creatine kinase. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: U/L
arithmetic mean (standard deviation)	-45.6 ( 58.24 )	9.5 ( 37.12 )	5.0 ( 20.34 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Sodium

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End point title

Change from Baseline in Clinical Chemistry Parameter: Sodium

End point description

This endpoint reported change from baseline to Month 6 in sodium. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: millimole per litre (mmol/L)
arithmetic mean (standard deviation)	-0.4 ( 2.51 )	-0.6 ( 2.79 )	-0.2 ( 2.91 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Potassium

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End point title

Change from Baseline in Clinical Chemistry Parameter: Potassium

End point description

This endpoint reported change from baseline to Month 6 in potassium. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: mmol/L
arithmetic mean (standard deviation)	-0.42 ( 0.356 )	-0.11 ( 0.571 )	-0.15 ( 0.411 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Chloride

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End point title

Change from Baseline in Clinical Chemistry Parameter: Chloride

End point description

This endpoint reported change from baseline to Month 6 in chloride. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: mmol/L
arithmetic mean (standard deviation)	-1.0 ( 1.22 )	0.4 ( 2.93 )	-0.9 ( 2.64 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Creatinine

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End point title

Change from Baseline in Clinical Chemistry Parameter: Creatinine

End point description

This endpoint reported change from baseline to Month 6 in creatinine. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: umol/L
arithmetic mean (standard deviation)	0.66 ( 5.062 )	1.10 ( 6.327 )	1.26 ( 1.965 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Plasma Oxalate

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End point title

Change from Baseline in Clinical Chemistry Parameter: Plasma Oxalate

End point description

This endpoint reported change from baseline to Month 6 in plasma oxalate. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subject analysed' signifies 'Overall number of subjects analysed'; 'n' signifies 'Number Analyzed' that is number of subjects with available data for particular timepoint, for the respective arms; and "99999" signifies that data for these categories were not evaluable as the number of subject for the respective category was 0.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	8	5
Units: umol/L
arithmetic mean (standard deviation)
PH1 (n=3,6,5)	-9.000 ( 10.5830 )	-5.667 ( 2.6583 )	-4.400 ( 4.3932 )
PH2 (n=0,2,0)	99999 ( 99999 )	-2.500 ( 0.7071 )	99999 ( 99999 )
PH3 (n=2,0,0)	-2.000 ( 1.4142 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Blood Urea Nitrogen

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End point title

Change from Baseline in Clinical Chemistry Parameter: Blood Urea Nitrogen

End point description

This endpoint reported change from baseline to Month 6 in blood urea nitrogen. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	8
Units: mmol/L
arithmetic mean (standard deviation)	0.56 ( 2.016 )	0.06 ( 1.999 )	-0.11 ( 1.082 )

No statistical analyses for this end point

Secondary: Change from Baseline in Clinical Chemistry Parameter: Cystatin C

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End point title

Change from Baseline in Clinical Chemistry Parameter: Cystatin C

End point description

This endpoint reported change from baseline to Month 6 in cystatin C. Safety population included all subjects who received at least 1 dose of study intervention. Here 'Number of subjects analysed' signified number of subject with available data for particular timepoint, in the respective arms.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	12	9
Units: milligrams per litre (mg/L)
arithmetic mean (standard deviation)	-0.120 ( 0.1595 )	-0.026 ( 0.1962 )	0.024 ( 0.1283 )

No statistical analyses for this end point

Secondary: Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)

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End point title

Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)

End point description

This endpoint was expected to report Cmax which is defined as maximum observed concentration. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples collected in paediatric subjects per protocol, hence these PK parameters were not estimated. The PK population included all subjects who had received at least 1 dose of study intervention (without major dosing violations) and had at least 1 evaluable postdose PK assessment.

End point type

Secondary

End point timeframe

Day 1: Postdose 0- to 4-hour and 4- to 24-hour, Days 2, 30, and 90: post dose, Day 150: predose and Day 150: postdose: 0- to 4-hour and 4- to 24-hour

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	0 ^[3]	0 ^[4]	0 ^[5]
Units: nanograms per millilitre (ng/mL)
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[3] - Cmax was not estimable due to limited sample collection.
[4] - Cmax was not estimable due to limited sample collection.
[5] - Cmax was not estimable due to limited sample collection.

No statistical analyses for this end point

Secondary: Plasma PK Parameters: Area Under the Concentration-time Curve Calculated to the Last Observable concentration at time t (AUCt)

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End point title

Plasma PK Parameters: Area Under the Concentration-time Curve Calculated to the Last Observable concentration at time t (AUCt)

End point description

This endpoint was expected to report AUCt which is defined as area under the concentration-time curve calculated to the last observable concentration at time t. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples collected in paediatric subjects per protocol, hence these PK parameters were not estimated. The PK population included all subjects who had received at least 1 dose of study intervention (without major dosing violations) and had at least 1 evaluable postdose PK assessment.

End point type

Secondary

End point timeframe

Day 1: Postdose 0- to 4-hour and 4- to 24-hour, Days 2, 30, and 90: post dose, Day 150: predose and Day 150: postdose: 0- to 4-hour and 4- to 24-hour

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	0 ^[6]	0 ^[7]	0 ^[8]
Units: hour*nanograms per millilitre
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[6] - AUCt was not estimable due to limited sample collection.
[7] - AUCt was not estimable due to limited sample collection.
[8] - AUCt was not estimable due to limited sample collection.

No statistical analyses for this end point

Secondary: Plasma PK Parameters: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞)

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End point title

Plasma PK Parameters: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞)

End point description

This endpoint was expected to report AUC∞ which is defined as area under the concentration-time curve from time zero to infinity. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples collected in paediatric subjects per protocol, hence these PK parameters were not estimated. The PK population included all subjects who had received at least 1 dose of study intervention (without major dosing violations) and had at least 1 evaluable postdose PK assessment.

End point type

Secondary

End point timeframe

Day 1: Postdose 0- to 4-hour and 4- to 24-hour, Days 2, 30, and 90: post dose, Day 150: predose and Day 150: postdose: 0- to 4-hour and 4- to 24-hour

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	0 ^[9]	0 ^[10]	0 ^[11]
Units: hour*nanograms per millilitre
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[9] - AUC∞ was not estimable due to limited sample collection.
[10] - AUC∞ was not estimable due to limited sample collection.
[11] - AUC∞ was not estimable due to limited sample collection.

No statistical analyses for this end point

Secondary: Percentage of Subjects with Spot Urinary Oxalate-to-Creatinine Ratio <=Upper Limit of Normal (ULN) or <=1.5*ULN at any time point through Month 6 in PH1, PH2, or PH3 Subject Subgroups

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End point title

Percentage of Subjects with Spot Urinary Oxalate-to-Creatinine Ratio <=Upper Limit of Normal (ULN) or <=1.5*ULN at any time point through Month 6 in PH1, PH2, or PH3 Subject Subgroups

End point description

This endpoint reported percentage of subjects from baseline to Month 6 Oxalate-to-creatinine Ratio less than and equal to (<=) upper limit of normal (ULN) or <=1.5*ULN at any time point through Month 6 in paediatric subjects (birth to 11 years of age) with genetically confirmed PH1, PH2, or PH3 subgroups. The MITT Population included all subjects who received at least 1 dose of study intervention and have at least 1 post-baseline spot urinary oxalate to creatinine ratio. Here 'Number of subject analysed' signifies 'Overall number of subjects analysed'; 'n' signifies 'Number Analyzed' that is number of subjects with available data for particular timepoint, for the respective arms; and "99999" signifies that data for these categories were not evaluable as the number of subject for the respective category was 0.

End point type

Secondary

End point timeframe

From baseline (week 0) through Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	13	9
Units: Percentage of subjects
number (not applicable)
PH1: <= 1.0 * ULN (n=3,9,8)	66.7	44.4	62.5
PH1: <= 1.5 * ULN (n=3,9,8)	100	88.9	100
PH2: <= 1.0 * ULN (n=0,4,1)	99999	50.0	0
PH2: <= 1.5 * ULN (n=0,4,1)	99999	75.0	100
PH3: <= 1.0 * ULN (n=2,0,0)	50.0	99999	99999
PH3: <= 1.5 * ULN (n=2,0,0)	100	99999	99999

No statistical analyses for this end point

Secondary: Change from Baseline in eGFR at Month 6 (only in subjects >=12 Months of age at Screening) in PH1, PH2, or PH3 subject subgroups

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End point title

Change from Baseline in eGFR at Month 6 (only in subjects >=12 Months of age at Screening) in PH1, PH2, or PH3 subject subgroups

End point description

This endpoint reported Change from Baseline in GFR estimated Cystatin C at Month 6 (only in subjects >=12 Months of age at Screening) in PH1, PH2, or PH3 subject subgroups. MITT Population included all subjects who received at least 1 dose of study intervention and have at least 1 post-baseline spot urinary oxalate to creatinine ratio. The eGFR was calculated using multivariate Schwartz equation using formula: eGFR=39.8*[ht/Scr]^0.456 [1.8/cysC]^0.418 [30/BUN]^0.0791.076^male[ht/1.4]^0.179 where ht (height) = metres, Scr (serum creatinine) = milligrams per decilitre (mg/dL), cysC (cystatin C) = mg/L, and BUN (blood urea nitrogen) = mg/dL. Here 'Number of subject analysed' signifies 'Overall number of subjects analysed'; 'n' signifies 'Number Analysed' i.e, number of subjects with available data for particular timepoint, for the respective arms; and "99999" signifies that data for these categories were not evaluable as number of subject for respective category was 0.

End point type

Secondary

End point timeframe

Baseline (Week 0), Month 6

End point values	Children 0 to <2 years	Children 2 to <6 years	Children 6 to 11 years
Number of subjects analysed	5	12	9
Units: millilitre/minute/standard surface area
arithmetic mean (standard deviation)
PH1: (n=3,8,8)	0.0 ( 17.06 )	0.3 ( 10.02 )	-0.8 ( 7.21 )
PH2: (n=0,4,1)	99999 ( 99999 )	3.5 ( 13.48 )	-7.0 ( 0 )
PH3: (n=2,0,0)	15.0 ( 9.90 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline (Week 0) to Month 6

Adverse event reporting additional description

AE: Any untoward medical occurrence in subject, temporally associated with use of study drug, whether or not considered related to study drug. TEAE: Any AE if they have an onset or worsen in severity after a subject receives the study. Safety population: All subjects who received at least 1 dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Children 0 to <2 years

Reporting group description

All subjects that included neonates (0 to <2 years) with PH and relatively intact renal function based upon eGFR and serum creatinine, received monthly dose of nedosiran (3.5 mg/kg, not to exceed 170 mg), subcutaneously from Day 1 though Month 6.

Reporting group title

Overall

Reporting group description

Reporting group title

Children 6 to 11 years

Reporting group description

Reporting group title

Children 2 to <6 years

Reporting group description

Serious adverse events	Children 0 to <2 years	Overall	Children 6 to 11 years	Children 2 to <6 years
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 5 (20.00%)	5 / 27 (18.52%)	1 / 9 (11.11%)	3 / 13 (23.08%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	1 / 9 (11.11%)	1 / 13 (7.69%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelocaliectasis
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Children 0 to <2 years	Overall	Children 6 to 11 years	Children 2 to <6 years
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	23 / 27 (85.19%)	7 / 9 (77.78%)	11 / 13 (84.62%)
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	1 / 5 (20.00%)	5 / 27 (18.52%)	2 / 9 (22.22%)	2 / 13 (15.38%)
occurrences all number	1	6	3	2
Pyrexia
subjects affected / exposed	4 / 5 (80.00%)	6 / 27 (22.22%)	2 / 9 (22.22%)	0 / 13 (0.00%)
occurrences all number	4	9	5	0
Injection site induration
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 5 (0.00%)	4 / 27 (14.81%)	0 / 9 (0.00%)	4 / 13 (30.77%)
occurrences all number	0	5	0	5
Epistaxis
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Rhinorrhoea
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Tonsillar hypertrophy
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0
Psychiatric disorders
Enuresis
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Irritability
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0
Tic
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Investigations
Cystatin C increased
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	2	2	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Hepatic enzyme increased
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Urinary sediment
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Immunisation reaction
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0
Skin laceration
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Headache
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Thrombocytopenia
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 5 (20.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	5	6	0	1
Diarrhoea
subjects affected / exposed	1 / 5 (20.00%)	4 / 27 (14.81%)	1 / 9 (11.11%)	2 / 13 (15.38%)
occurrences all number	1	5	1	3
Constipation
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Vomiting
subjects affected / exposed	2 / 5 (40.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	2	2	0	0
Odynophagia
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Nausea
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Skin and subcutaneous tissue disorders
Rash vesicular
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0
Rash
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	2	0	2
Macule
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	0 / 5 (0.00%)	3 / 27 (11.11%)	2 / 9 (22.22%)	1 / 13 (7.69%)
occurrences all number	0	6	4	2
Haematuria
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	1 / 9 (11.11%)	1 / 13 (7.69%)
occurrences all number	0	2	1	1
Dysuria
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	2 / 9 (22.22%)	0 / 13 (0.00%)
occurrences all number	0	2	2	0
Renal colic
subjects affected / exposed	1 / 5 (20.00%)	3 / 27 (11.11%)	2 / 9 (22.22%)	0 / 13 (0.00%)
occurrences all number	1	3	2	0
Nephrolithiasis
subjects affected / exposed	2 / 5 (40.00%)	3 / 27 (11.11%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	6	7	1	0
Glycosuria
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Renal disorder
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Urinary incontinence
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	2 / 13 (15.38%)
occurrences all number	0	2	0	2
Flank pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	2 / 13 (15.38%)
occurrences all number	0	2	0	2
Influenza
subjects affected / exposed	2 / 5 (40.00%)	3 / 27 (11.11%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	2	3	0	1
Respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	2 / 13 (15.38%)
occurrences all number	0	2	0	2
Nasopharyngitis
subjects affected / exposed	2 / 5 (40.00%)	4 / 27 (14.81%)	0 / 9 (0.00%)	2 / 13 (15.38%)
occurrences all number	4	8	0	4
Upper respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	3 / 27 (11.11%)	0 / 9 (0.00%)	3 / 13 (23.08%)
occurrences all number	0	8	0	8
Croup infectious
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
COVID-19
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Urinary tract infection
subjects affected / exposed	1 / 5 (20.00%)	3 / 27 (11.11%)	1 / 9 (11.11%)	1 / 13 (7.69%)
occurrences all number	1	4	2	1
Escherichia urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	4	4	0
Gastroenteritis
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	2	2	0	0
Scarlet fever
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Otitis media acute
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Hepatitis A
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Impetigo
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Urinary tract infection pseudomonal
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	1	1	0
Tonsillitis
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	1 / 9 (11.11%)	0 / 13 (0.00%)
occurrences all number	0	2	2	0
Metabolism and nutrition disorders
Iron deficiency
subjects affected / exposed	1 / 5 (20.00%)	2 / 27 (7.41%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	1	3	0	2
Obesity
subjects affected / exposed	0 / 5 (0.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	1 / 13 (7.69%)
occurrences all number	0	1	0	1
Vitamin D deficiency
subjects affected / exposed	1 / 5 (20.00%)	1 / 27 (3.70%)	0 / 9 (0.00%)	0 / 13 (0.00%)
occurrences all number	1	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Dec 2021

Amendment 1, version 2.0: The 15-Apr-2021 (Original Protocol, version 1.0) version of the protocol was amended to expand the population to include 6- to 11-year-old subjects. Other principal changes included changing the primary objective from safety to efficacy, adding pregnancy and contraception requirements, adding a maximum dose of 170 mg, updating the number of planned subjects from 15 to 25, and clarifying that the efficacy endpoints were presented by PH1, PH2, or PH3 subgroups. 1) Expanded population to include 6- to 11-year-old subjects. 2) Updated the primary endpoint to efficacy based upon spot urinary oxalate-to-creatinine ratio; safety endpoint was moved to secondary. 3) Added a maximum dose of 170 mg. 4) Clarified for subjects >=6 months of age at Screening, the dose was to remain constant throughout the study (i.e., the dose administered on Day 1 will be the dose administered at all following visits regardless of any change in body weight). 5) Updated number of planned subjects from 15 to 25. 6) Clarified that the secondary efficacy endpoint related to normalisation of spot urinary oxalate-to-creatinine ratio includes subjects with spot urinary oxalate-to-creatinine ratio <= the ULN or <=1.5 x ULN at any time point. 7) Clarified that the efficacy endpoints will be presented by PH1, PH2, or PH3 subgroups. 8) Other study related and administrative changes.

01 Nov 2022

Amendment 2, version 3.0: The 21-Dec-2021 version of the protocol was amended to expand the population to include <2-year-old subjects. 1) Expanded population to include 0- to 2-year-old subjects. 2) Corrected errors in the Schedule of assessment relating to recording of fluid intake. 3) Other administrative updates.

23 Feb 2023

Amendment 3, version 4.0: 1) Removed the 10 kg minimum body weight from the inclusion criteria. 2) Added text regarding maximum blood volume collection allowed based on body weight and to direct the Investigator to the Laboratory Manual for the blood draw priority list. 3) Updated study duration from 18 to 24 months. 4) Added text to allow for interval weight gain dose adjustments in concomitant therapy regimens. 5) Updated text to clarify the range of 4 to 7 days for reporting of fluid intake. 6) Added additional text denoting differences in response between participants with PH1 and PH2 in study. 7) Added text regarding spot urine collection in infants. 8) Added text to allow for interval weight gain dose adjustments in concomitant therapy regimens. 9) Other administrative updates

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2 Open-Label Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Nedosiran in Pediatric Patients from Birth to 11 Years of Age with Primary Hyperoxaluria and Relatively Intact Renal Function

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

Primary: Percent change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

Primary: Absolute change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

Primary: Absolute change from Baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in PH1, PH2, or PH3 subject subgroups

Secondary: Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Secondary: Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Secondary: Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature

Secondary: Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature

Secondary: Change from Baseline in 12-lead ECG- RR Interval

Secondary: Change from Baseline in 12-lead ECG- RR Interval

Secondary: Change from Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate

Secondary: Change from Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate

Secondary: Change from Baseline in 12-lead ECG-QTcF Interval, Aggregate

Secondary: Change from Baseline in 12-lead ECG-QTcF Interval, Aggregate

Secondary: Change from Baseline in 12-lead ECG-QT Interval, Aggregate

Secondary: Change from Baseline in 12-lead ECG-QT Interval, Aggregate

Secondary: Change from Baseline in 12-lead ECG-QRS Duration, Aggregate

Secondary: Change from Baseline in 12-lead ECG-QRS Duration, Aggregate

Secondary: Change from Baseline in 12-lead ECG-PR Interval, Aggregate

Secondary: Change from Baseline in 12-lead ECG-PR Interval, Aggregate

Secondary: Change from Baseline in Subjects with Significant Findings- Physical Examination

Secondary: Change from Baseline in Subjects with Significant Findings- Physical Examination

Secondary: Change from Baseline in vital sign assessment-Body Mass Index

Secondary: Change from Baseline in vital sign assessment-Body Mass Index

Secondary: Change from Baseline in vital sign assessment-Weight

Secondary: Change from Baseline in vital sign assessment-Weight

Secondary: Change from Baseline in vital sign assessment- Height

Secondary: Change from Baseline in vital sign assessment- Height

Secondary: Change from Baseline in vital sign assessment-Oral Body Temperature

Secondary: Change from Baseline in vital sign assessment-Oral Body Temperature

Secondary: Change from Baseline in vital sign assessment-Respiratory Rate

Secondary: Change from Baseline in vital sign assessment-Respiratory Rate

Secondary: Change from Baseline in vital sign assessment-Heart Rate

Secondary: Change from Baseline in vital sign assessment-Heart Rate

Secondary: Change from Baseline in Haematology assessment: Haemoglobin

Secondary: Change from Baseline in Haematology assessment: Haemoglobin

Secondary: Change from Baseline in vital sign assessment-Systolic Blood Pressure and Diastolic Blood Pressure

Secondary: Change from Baseline in vital sign assessment-Systolic Blood Pressure and Diastolic Blood Pressure

Secondary: Change from Baseline in Haematology assessment: Erythrocytes

Secondary: Change from Baseline in Haematology assessment: Erythrocytes

Secondary: Change from Baseline in Haematology assessment: Haematocrit

Secondary: Change from Baseline in Haematology assessment: Haematocrit

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Volume

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Volume

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Haemoglobin

Secondary: Change from Baseline in Haematology assessment: Erythrocytes Mean Corpuscular Haemoglobin

Secondary: Change from Baseline in Haematology Assessment: Erythrocytes Mean Corpuscular Haemoglobin Concentration

Secondary: Change from Baseline in Haematology Assessment: Erythrocytes Mean Corpuscular Haemoglobin Concentration

Secondary: Change from Baseline in Haematology assessment: Reticulocytes

Secondary: Change from Baseline in Haematology assessment: Reticulocytes

Secondary: Change from Baseline in Haematology assessment: Platelets

Secondary: Change from Baseline in Haematology assessment: Platelets

Secondary: Change from Baseline in Haematology assessment: Leukocytes

Secondary: Change from Baseline in Haematology assessment: Leukocytes

Secondary: Change from Baseline in Haematology assessment: Lymphocytes

Secondary: Change from Baseline in Haematology assessment: Lymphocytes

Secondary: Change from Baseline in Haematology assessment: Monocytes

Secondary: Change from Baseline in Haematology assessment: Monocytes

Secondary: Change from Baseline in Haematology assessment: Mean Platelet Volume

Secondary: Change from Baseline in Haematology assessment: Mean Platelet Volume

Secondary: Change from Baseline in Haematology assessment: Basophils

Secondary: Change from Baseline in Haematology assessment: Basophils

Secondary: Change from Baseline in Haematology assessment: Eosinophils

Secondary: Change from Baseline in Haematology assessment: Eosinophils

Secondary: Change from Baseline in Haematology assessment: Neutrophils

Secondary: Change from Baseline in Haematology assessment: Neutrophils

Secondary: Change from Baseline in Haematology assessment: Eosinophils/Leukocytes

Secondary: Change from Baseline in Haematology assessment: Eosinophils/Leukocytes

Secondary: Change from Baseline in Haematology assessment: Monocytes/Leukocytes

Secondary: Change from Baseline in Haematology assessment: Monocytes/Leukocytes

Clinical Trial Results:
A Phase 2 Open-Label Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Nedosiran in Pediatric Patients from Birth to 11 Years of Age with Primary Hyperoxaluria and Relatively Intact Renal Function