Investigating the Long-term Efficacy and Safety of Two Do... | NCT01927861

ID	Type	Description	Link
U1111-1131-5892	Other Identifier	WHO
JapicCTI-132336	Registry Identifier	JAPIC

Label	Type	Description	Intervention Names
0.033 mg/kg/day	Experimental		Drug: somatropin
0.066 mg/kg/day	Experimental		Drug: somatropin

Name	Type	Description	Arm Group Labels	Other Names
somatropin	Drug	Administered subcutaneously (s.c., under the skin) in a daily regimen for at least 104 weeks. Subject will be offered to continue treatment for another 104 weeks.

Measure	Description	Time Frame
Change in Height SDS (Japanese National Reference Data)	Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline height SDS as a covariate. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the last observation carried forward (LOCF) method.	Baseline, week 104

Measure	Description	Time Frame
Height Velocity SDS	Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Asahikawa, Hokkaido		078-8510	Japan
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
32269181	Result	Horikawa R, Ogata T, Matsubara Y, Yokoya S, Ogawa Y, Nishijima K, Endo T, Ozono K. Long-term efficacy and safety of two doses of Norditropin(R) (somatropin) in Noonan syndrome: a 4-year randomized, double-blind, multicenter trial in Japanese patients. Endocr J. 2020 Aug 28;67(8):803-818. doi: 10.1507/endocrj.EJ19-0371. Epub 2020 May 9.
29109363

Label	URL
Clinical Trials at Novo Nordisk	View source

ID	Title	Description
FG000	NN-220 0.033 mg/kg/Day	Participants received subcutaneous (s.c.) injection of NN-220, 0.033 milligrams per kilogram per day (mg/kg/day) once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
FG001	NN-220 0.066 mg/kg/Day

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 26, 2018	Aug 19, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Height SDS (Japanese National Reference Data)

Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline height SDS as a covariate. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the last observation carried forward (LOCF) method.

FAS.

Posted

Least Squares Mean

Standard Error

Standard deviation score

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG00025 OG00126

Title

Denominators

Categories

Title	Measurements
	OG0000.84± 0.09 OG0011.47± 0.09

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The change from baseline (week 0) in the height SDS after 104 weeks of treatment was analysed using an ANCOVA model with treatment as a fixed effect and baseline height SDS as a covariate.	ANCOVA		< 0.0001		Treatment difference	0.63			2-Sided	95	0.38	0.88					Other

Secondary

Height Velocity SDS

Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 52) and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Baseline to week 52

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Secondary

Height Velocity SDS

Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 104) and height at week 52 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Week 52 to week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Secondary

Height Velocity

FAS.

Posted

Mean

Standard Deviation

Centimeters per year (cm/year)

Baseline to week 52

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Height Velocity

FAS.

Posted

Mean

Standard Deviation

cm/year

Week 52 to week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Incidence of Treatment Emergent Adverse Events

A treatment emergent adverse event (TEAE; for the pivotal phase) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than the date of visit 12 (104 weeks; end of pivotal phase). For withdrawal participants (if any), an adverse event with onset date no later than 7 days after the last day of NN-220 treatment was included.

Safety analysis set (SAS) which included all participants who received at least one dose of trial product (NN-220, 0.033 mg/kg/day or NN-220, 0.066 mg/kg/day).

Posted

Number

Events

During 104 weeks of treatment

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts

Secondary

Change in IGF-I (Insulin-like Growth Factor-I)

Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 104 weeks of treatment. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Nanograms per milliliter (ng/mL)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in HbA1c (Glycosylated Haemoglobin)

Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment.

SAS.

Posted

Mean

Standard Deviation

Percentage of HbA1c

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Erythrocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

10^12 cells per liter (10^12 cells/L)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

10^9 cells per liter (10^9 cells/L)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Haemoglobin)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Millimoles per liter (mmol/L)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Haematocrit)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of red blood cells

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Neutrophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of neutrophils

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Lymphocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of lymphocytes

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Monocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of monocytes

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Eosinophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of eosinophils

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Basophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of basophils

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)

Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL (low-density lipoprotein) cholesterol and HDL (high-density lipoprotein) cholesterol. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

mmol/L

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (r-GTP) and alkaline phosphatase. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Units per liter (U/L)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Total Protein)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Grams per deciliter (g/dL)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - blood urea nitrogen, sodium, potassium, chloride, total calcium and phosphorus. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

mmol/L

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Creatinine)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - creatinine. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Micromoles per liter (umol/L)

Baseline, Week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT

AUC (area under the curve) of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the oral glucose tolerance test (OGTT). Change from baseline results are presented as 'ratio to baseline'.

SAS.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio of AUC

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT

AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 104 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.

SAS. Number analyzed = participants with available data.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio of AUC

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Bone Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the radius, ulna and short bones (RUS) score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age.

SAS.

Posted

Mean

Standard Deviation

Years

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Bone Age/Chronological Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Change from baseline (week 0) in bone age/chronological age.

SAS.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Yearly Change in Bone Age/Change in Chronological Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from baseline (week 0) in bone age/change in chronological age was presented.

SAS.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Baseline, week 52

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Yearly Change in Bone Age/Change in Chronological Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 52 in bone age/change in chronological age was presented.

SAS.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Week 52, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)

Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Millimeters of mercury (mmHg)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Vital Signs (Pulse)

Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Beats per minute (beats/min)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Urinalysis (Protein, Glucose and Occult Blood)

The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 104 and categorised as negative, trace, 1+, 2+ and 3+. Missing values were imputed using the LOCF method. Number of participants in each category at baseline and week 104 are presented.

SAS.

Posted

Count of Participants

Participants

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Blood Coagulation Test (Prothrombin Time and APTT)

Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: Prothrombin time and APTT (activated partial thromboplastin time). Missing values were imputed using the LOCF method.

SAS.

Posted

Median

Full Range

Second (sec)

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in ECG

The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 104 and categorised as normal, abnormal NCS (not clinically significant) or abnormal CS (clinically significant). Number of participants in each ECG category at baseline and week 104 are presented. Missing values were imputed using the LOCF method.

SAS.

Posted

Count of Participants

Participants

Baseline, week 104

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Height SDS (Japanese National Reference Data)

Height SDS was calculated using the formula: SDS = (height - mean)/SD, where height was the height variable measured, mean and SD of height by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts

Secondary

Change in Height SDS (Noonan Syndrome Reference Data in Japanese)

Height SDS was calculated using the formula: Z=[(value/M)^L-1]/(S*L); where L, M and S are skewness (L), median (M) and coefficient of variation (S) of Japanese Noonan syndrome' height provided for each sex and age. For each participant, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The scores were centered around zero. Positive SDS indicated greater height and negative SDS indicated lesser height than the mean of the reference population. The change from baseline (week 0) in the height SDS after 208 weeks of treatment was analysed. Positive value in change from baseline indicated that SDS was better than baseline SDS. Missing values were imputed using the LOCF method.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Secondary

Height Velocity

FAS.

Posted

Mean

Standard Deviation

cm/year

Week 104 to week 156

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Height Velocity

FAS.

Posted

Mean

Standard Deviation

cm/year

Week 156 to week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Height Velocity SDS

Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 156) and height at week 104 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Week 104 to week 156

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Secondary

Height Velocity SDS

Height velocity is change in height per year. The height velocity was calculated as the difference between current height (week 208) and height at week 156 divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using the formula: SDS = (height velocity - mean)/SD, where height velocity was the height velocity variable measured, mean and SD of height velocity by sex and age for the reference population. The scores were centered around zero. Positive SDS indicated greater height velocity and negative SDS indicated lesser height velocity than the mean of the reference population.

FAS.

Posted

Mean

Standard Deviation

Standard deviation score

Week 156 to week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Secondary

Incidence of Treatment Emergent AEs

A treatment emergent AE (TEAE) was defined as an event that had onset date on or after the date of visit 2 (week 0; start of treatment) and no later than 7 days after the last day of NN-220 treatment.

SAS.

Posted

Number

Events

Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in IGF-I

Change from baseline (within 4 weeks prior to week 0) in IGF-I was evaluated after 208 weeks of treatment. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

ng/mL

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in HbA1c

Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Percentage of HbA1c

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Erythrocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

10^12 cells/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline, Week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Haemoglobin)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

mmol/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Haematocrit)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of red blood cells

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Neutrophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of neutrophils

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Lymphocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of lymphocytes

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Monocytes)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of monocytes

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Eosinophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of eosinophils

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Haematology: Basophils)

Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

Percentage of basophils

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)

Change from baseline (within 4 weeks prior to week 0) in lipids: total cholesterol, LDL cholesterol and HDL cholesterol. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

mmol/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - AST, ALT, r-GTP and alkaline phosphatase. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

U/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Total Protein)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

g/dL

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

mmol/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Clinical Laboratory Tests (Biochemistry: Creatinine)

Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - creatinine. Missing values were imputed using the LOCF method.

SAS.

Posted

Mean

Standard Deviation

umol/L

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT

AUC of glucose was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of glucose: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.

SAS. Number analyzed = participants with available data.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio of AUC

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT

AUC of insulin was calculated by the trapezoidal method. Change from baseline (within 4 weeks prior to week 0) in glucose tolerance (AUC of insulin: 30, 60, 90 and 120 min after oral glucose load) at week 208 was evaluated based on the OGTT. Change from baseline results are presented as 'ratio to baseline'.

SAS. Number analyzed = participants with available data.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio of AUC

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Bone Age

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Years

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Bone Age/Chronological Age

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Yearly Change in Bone Age/Change in Chronological Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 104 in bone age/change in chronological age was presented.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Week 104, week 156

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Yearly Change in Bone Age/Change in Chronological Age

X-ray picture of carpal bones of left hand was taken for bone age determination. Centralised evaluation of bone age was done by the RUS score method of Tanner-Whitehouse II (TW2). Yearly change from week 156 in bone age/change in chronological age was presented.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

Ratio (bone age/chronological age)

Week 156, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)

Systolic and diastolic blood pressure were measured after a 5-minute rest in sitting position. Change from baseline (week 0) in systolic blood pressure and diastolic blood pressure. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

mmHg

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Vital Signs (Pulse)

Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse. Missing values were imputed using the LOCF method.

SAS. Number analyzed = participants with available data.

Posted

Mean

Standard Deviation

beats/min

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in Urinalysis (Protein, Glucose and Occult Blood)

The urinalysis was the measurements of protein, glucose, and occult blood at baseline (within 4 weeks prior to week 0) and week 208 and categorised as negative, trace, 1+, 2+ and 3+. Number of participants in each category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.

SAS.

Posted

Count of Participants

Participants

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants

Secondary

Change in Blood Coagulation Test (Prothrombin Time and APTT)

Change from baseline (within 4 weeks prior to week 0) in blood coagulation test parameters: prothrombin time and APTT. Missing values were imputed using the LOCF method.

SAS.

Posted

Median

Full Range

sec

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Secondary

Change in ECG

The ECG was recorded after a 3-minute rest in supine position at baseline (within 4 weeks prior to week 0) and week 208 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 208 are presented. Missing values were imputed using the LOCF method.

SAS.

Posted

Count of Participants

Participants

Baseline, week 208

ID	Title	Description
OG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
OG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).

Units	Counts
Participants	OG000

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arnold-Chiari malformation	Congenital, familial and genetic disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Conductive deafness	Ear and labyrinth disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Craniosynostosis	Congenital, familial and genetic disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0011 events1 affected26 at risk
Dental caries	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected26 at risk
Febrile convulsion	Nervous system disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Gastroenteritis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Hamartoma	Congenital, familial and genetic disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Head banging	Psychiatric disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Phimosis	Congenital, familial and genetic disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Pneumonia	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Pneumonia mycoplasmal	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0011 events1 affected26 at risk
Polymyositis	Musculoskeletal and connective tissue disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Pulmonary artery therapeutic procedure	Surgical and medical procedures	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Salivary gland calculus	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected26 at risk
Supernumerary teeth	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Testicular swelling	Reproductive system and breast disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Tonsillitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk
Velopharyngeal incompetence	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected26 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG00110 events2 affected26 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0012 events2 affected26 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0018 events3 affected26 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0013 events2 affected26 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0004 events3 affected25 at risk EG0013 events2 affected26 at risk
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected26 at risk
Bronchitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0005 events4 affected25 at risk EG00112 events7 affected26 at risk
Bronchitis bacterial	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected26 at risk
Chillblains	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0004 events2 affected25 at risk EG0010 events0 affected26 at risk
Conjunctivitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0006 events5 affected25 at risk EG0016 events6 affected26 at risk
Conjunctivitis allergic	Eye disorders	MedDRA 18	Systematic Assessment	EG00011 events6 affected25 at risk EG0015 events5 affected26 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0012 events2 affected26 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0008 events6 affected25 at risk EG0015 events3 affected26 at risk
Dental caries	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0004 events4 affected25 at risk EG00111 events4 affected26 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected26 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG00012 events7 affected25 at risk EG0014 events3 affected26 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0012 events2 affected26 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0004 events3 affected25 at risk EG00113 events8 affected26 at risk
Enteritis	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0003 events2 affected25 at risk EG0011 events1 affected26 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0004 events3 affected25 at risk EG0011 events1 affected26 at risk
Gastroenteritis	Infections and infestations	MedDRA 18	Systematic Assessment	EG00014 events8 affected25 at risk EG00133 events14 affected26 at risk
Gingivitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0011 events1 affected26 at risk
Headache	Nervous system disorders	MedDRA 18	Systematic Assessment	EG00010 events6 affected25 at risk EG0015 events2 affected26 at risk
Hordeolum	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0015 events3 affected26 at risk
Hyperinsulinaemia	Metabolism and nutrition disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected26 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0013 events2 affected26 at risk
Impetigo	Infections and infestations	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0012 events2 affected26 at risk
Influenza	Infections and infestations	MedDRA 18	Systematic Assessment	EG00034 events20 affected25 at risk EG00131 events18 affected26 at risk
Miliaria	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG00110 events5 affected26 at risk
Molluscum contagiosum	Infections and infestations	MedDRA 18	Systematic Assessment	EG0003 events3 affected25 at risk EG0011 events1 affected26 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG000115 events19 affected25 at risk EG001121 events21 affected26 at risk
Nausea	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0011 events1 affected26 at risk
Otitis media	Infections and infestations	MedDRA 18	Systematic Assessment	EG0009 events7 affected25 at risk EG0019 events8 affected26 at risk
Otitis media acute	Infections and infestations	MedDRA 18	Systematic Assessment	EG0006 events4 affected25 at risk EG0011 events1 affected26 at risk
Pharyngitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0003 events2 affected25 at risk EG0016 events5 affected26 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected26 at risk
Pyrexia	General disorders	MedDRA 18	Systematic Assessment	EG00024 events9 affected25 at risk EG00112 events9 affected26 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0003 events3 affected25 at risk EG0010 events0 affected26 at risk
Rhinitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0001 events1 affected25 at risk EG0017 events4 affected26 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0004 events4 affected25 at risk EG0014 events4 affected26 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG0003 events2 affected25 at risk EG0013 events3 affected26 at risk
Seasonal allergy	Immune system disorders	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0011 events1 affected26 at risk
Sinusitis	Infections and infestations	MedDRA 18	Systematic Assessment	EG00014 events5 affected25 at risk EG0012 events2 affected26 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected26 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected26 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0016 events5 affected26 at risk
Streptococcal infection	Infections and infestations	MedDRA 18	Systematic Assessment	EG0003 events2 affected25 at risk EG0014 events3 affected26 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected26 at risk
Tinea pedis	Infections and infestations	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0019 events5 affected26 at risk
Toothache	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected26 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18	Systematic Assessment	EG00038 events8 affected25 at risk EG00143 events9 affected26 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 18	Systematic Assessment	EG00035 events7 affected25 at risk EG00130 events9 affected26 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 18	Systematic Assessment	EG0008 events5 affected25 at risk EG0012 events2 affected26 at risk
Varicella	Infections and infestations	MedDRA 18	Systematic Assessment	EG0002 events2 affected25 at risk EG0015 events5 affected26 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18	Systematic Assessment	EG0009 events4 affected25 at risk EG0013 events3 affected26 at risk

ID	Term
D030342	Genetic Diseases, Inborn
D009634	Noonan Syndrome

ID	Term
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D019465	Craniofacial Abnormalities
D009139	Musculoskeletal Abnormalities
D009140	Musculoskeletal Diseases
D006330	Heart Defects, Congenital
D018376	Cardiovascular Abnormalities
D002318	Cardiovascular Diseases
D006331	Heart Diseases
D000013	Congenital Abnormalities
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D013006	Growth Hormone
D010908	Pituitary Hormones, Anterior
D010907	Pituitary Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	NN-220 0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
BG001	NN-220 0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0.033 mg/kg/Day	Participants received s.c. injection of NN-220, 0.033 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).	0	25	9	25	24	25
EG001	0.066 mg/kg/Day	Participants received s.c. injection of NN-220, 0.066 mg/kg/day once daily for 234 weeks (104 weeks of pivotal phase + 104 weeks of extension phase + 26 weeks extended treatment phase).	0	26	10	26	26	26