Trial Outcomes & Findings for Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome (NCT NCT01927861)
NCT ID: NCT01927861
Last Updated: 2020-08-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
51 participants
Primary outcome timeframe
Baseline, week 104
Results posted on
2020-08-10
Participant Flow
The trial was conducted at 26 sites in Japan.
Participants were assigned to treatment for 104 weeks in the pivotal phase and for further 104 weeks in the extension phase and were offered to continue treatment in the extended treatment phase for 26 weeks.
Participant milestones
| Measure |
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).
|
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).
|
|---|---|---|
|
Pivotal Phase (104 Weeks)
STARTED
|
25
|
26
|
|
Pivotal Phase (104 Weeks)
COMPLETED
|
25
|
26
|
|
Pivotal Phase (104 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Extension Phase (104 Weeks)
STARTED
|
25
|
26
|
|
Extension Phase (104 Weeks)
COMPLETED
|
25
|
23
|
|
Extension Phase (104 Weeks)
NOT COMPLETED
|
0
|
3
|
|
Extended Treatment Phase (26 Weeks)
STARTED
|
15
|
14
|
|
Extended Treatment Phase (26 Weeks)
COMPLETED
|
15
|
14
|
|
Extended Treatment Phase (26 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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).
|
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).
|
|---|---|---|
|
Extension Phase (104 Weeks)
Adverse Event
|
0
|
2
|
|
Extension Phase (104 Weeks)
Unclassified
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
6.57 years
STANDARD_DEVIATION 2.42 • n=25 Participants
|
6.06 years
STANDARD_DEVIATION 2.25 • n=26 Participants
|
6.31 years
STANDARD_DEVIATION 2.32 • n=51 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=25 Participants
|
8 Participants
n=26 Participants
|
19 Participants
n=51 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=25 Participants
|
18 Participants
n=26 Participants
|
32 Participants
n=51 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Asian
|
25 Participants
n=25 Participants
|
26 Participants
n=26 Participants
|
51 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=51 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Height standard deviation score (SDS) (Japanese national reference data)
|
-3.24 Standard deviation score
STANDARD_DEVIATION 0.76 • n=25 Participants
|
-3.25 Standard deviation score
STANDARD_DEVIATION 0.71 • n=26 Participants
|
-3.24 Standard deviation score
STANDARD_DEVIATION 0.73 • n=51 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 104Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Height SDS (Japanese National Reference Data)
|
0.84 Standard deviation score
Standard Error 0.09
|
1.47 Standard deviation score
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline to week 52Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity SDS
|
2.80 Standard deviation score
Standard Deviation 1.13
|
5.01 Standard deviation score
Standard Deviation 1.92
|
SECONDARY outcome
Timeframe: Week 52 to week 104Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity SDS
|
0.58 Standard deviation score
Standard Deviation 1.59
|
2.65 Standard deviation score
Standard Deviation 1.76
|
SECONDARY outcome
Timeframe: Baseline to week 52Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity
|
7.88 Centimeters per year (cm/year)
Standard Deviation 0.87
|
9.90 Centimeters per year (cm/year)
Standard Deviation 1.49
|
SECONDARY outcome
Timeframe: Week 52 to week 104Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity
|
6.20 cm/year
Standard Deviation 0.95
|
7.99 cm/year
Standard Deviation 1.20
|
SECONDARY outcome
Timeframe: During 104 weeks of treatmentPopulation: 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).
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Incidence of Treatment Emergent Adverse Events
|
265 Events
|
306 Events
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in IGF-I (Insulin-like Growth Factor-I)
|
90.4 Nanograms per milliliter (ng/mL)
Standard Deviation 65.5
|
159.1 Nanograms per milliliter (ng/mL)
Standard Deviation 88.0
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 104 weeks of treatment.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in HbA1c (Glycosylated Haemoglobin)
|
0.14 Percentage of HbA1c
Standard Deviation 0.18
|
0.13 Percentage of HbA1c
Standard Deviation 0.20
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
|
0.106 10^12 cells per liter (10^12 cells/L)
Standard Deviation 0.300
|
0.165 10^12 cells per liter (10^12 cells/L)
Standard Deviation 0.234
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Leukocytes
|
-0.69 10^9 cells per liter (10^9 cells/L)
Standard Deviation 2.28
|
-1.01 10^9 cells per liter (10^9 cells/L)
Standard Deviation 1.77
|
|
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Thrombocytes
|
-6.9 10^9 cells per liter (10^9 cells/L)
Standard Deviation 60.2
|
-29.0 10^9 cells per liter (10^9 cells/L)
Standard Deviation 63.2
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
|
0.26 Millimoles per liter (mmol/L)
Standard Deviation 0.46
|
0.32 Millimoles per liter (mmol/L)
Standard Deviation 0.55
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
|
0.85 Percentage of red blood cells
Standard Deviation 2.11
|
0.94 Percentage of red blood cells
Standard Deviation 1.93
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
|
-4.28 Percentage of neutrophils
Standard Deviation 11.44
|
4.50 Percentage of neutrophils
Standard Deviation 9.01
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
|
2.80 Percentage of lymphocytes
Standard Deviation 9.07
|
-4.73 Percentage of lymphocytes
Standard Deviation 8.73
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Monocytes)
|
0.38 Percentage of monocytes
Standard Deviation 1.41
|
0.39 Percentage of monocytes
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
|
0.99 Percentage of eosinophils
Standard Deviation 2.95
|
-0.05 Percentage of eosinophils
Standard Deviation 1.33
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Basophils)
|
0.10 Percentage of basophils
Standard Deviation 0.36
|
-0.07 Percentage of basophils
Standard Deviation 0.27
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Total cholesterol
|
0.073 mmol/L
Standard Deviation 0.655
|
-0.110 mmol/L
Standard Deviation 0.371
|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
LDL cholesterol
|
0.040 mmol/L
Standard Deviation 0.521
|
-0.120 mmol/L
Standard Deviation 0.323
|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
HDL cholesterol
|
-0.020 mmol/L
Standard Deviation 0.212
|
-0.034 mmol/L
Standard Deviation 0.210
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
AST
|
-3.6 Units per liter (U/L)
Standard Deviation 2.9
|
-6.0 Units per liter (U/L)
Standard Deviation 4.3
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
ALT
|
-1.04 Units per liter (U/L)
Standard Deviation 3.10
|
-1.73 Units per liter (U/L)
Standard Deviation 4.20
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
r-GTP
|
0.4 Units per liter (U/L)
Standard Deviation 1.6
|
-3.7 Units per liter (U/L)
Standard Deviation 19.4
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Alkaline phosphatase
|
73.8 Units per liter (U/L)
Standard Deviation 76.3
|
124.3 Units per liter (U/L)
Standard Deviation 124.0
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
|
0.02 Grams per deciliter (g/dL)
Standard Deviation 0.38
|
-0.05 Grams per deciliter (g/dL)
Standard Deviation 0.27
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Blood urea nitrogen
|
-0.17 mmol/L
Standard Deviation 0.38
|
-0.21 mmol/L
Standard Deviation 0.44
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Sodium
|
-0.3 mmol/L
Standard Deviation 2.4
|
-0.2 mmol/L
Standard Deviation 2.6
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Potassium
|
-0.03 mmol/L
Standard Deviation 0.32
|
-0.15 mmol/L
Standard Deviation 0.41
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Chloride
|
-0.8 mmol/L
Standard Deviation 2.3
|
-1.3 mmol/L
Standard Deviation 1.9
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Total calcium
|
0.00 mmol/L
Standard Deviation 0.08
|
0.01 mmol/L
Standard Deviation 0.07
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Phosphorus
|
0.124 mmol/L
Standard Deviation 0.125
|
0.129 mmol/L
Standard Deviation 0.141
|
SECONDARY outcome
Timeframe: Baseline, Week 104Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - creatinine. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
|
1.8 Micromoles per liter (umol/L)
Standard Deviation 3.5
|
2.5 Micromoles per liter (umol/L)
Standard Deviation 3.4
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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'.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
|
0.98 Ratio of AUC
Geometric Coefficient of Variation 12.19
|
1.04 Ratio of AUC
Geometric Coefficient of Variation 17.75
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
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'.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
|
1.25 Ratio of AUC
Geometric Coefficient of Variation 45.08
|
1.72 Ratio of AUC
Geometric Coefficient of Variation 85.78
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Bone Age
|
2.07 Years
Standard Deviation 0.80
|
2.63 Years
Standard Deviation 0.94
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Bone Age/Chronological Age
|
0.047 Ratio (bone age/chronological age)
Standard Deviation 0.127
|
0.133 Ratio (bone age/chronological age)
Standard Deviation 0.127
|
SECONDARY outcome
Timeframe: Baseline, week 52Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Yearly Change in Bone Age/Change in Chronological Age
|
0.93 Ratio (bone age/chronological age)
Standard Deviation 0.66
|
1.28 Ratio (bone age/chronological age)
Standard Deviation 0.70
|
SECONDARY outcome
Timeframe: Week 52, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Yearly Change in Bone Age/Change in Chronological Age
|
1.15 Ratio (bone age/chronological age)
Standard Deviation 0.57
|
1.38 Ratio (bone age/chronological age)
Standard Deviation 0.91
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Diastolic blood pressure
|
2.3 Millimeters of mercury (mmHg)
Standard Deviation 13.2
|
6.3 Millimeters of mercury (mmHg)
Standard Deviation 15.8
|
|
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Systolic blood pressure
|
5.5 Millimeters of mercury (mmHg)
Standard Deviation 11.9
|
4.1 Millimeters of mercury (mmHg)
Standard Deviation 12.1
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS. Number analyzed = participants with available data.
Pulse was measured after a 5-minute rest in sitting position. Change from baseline (week 0) in pulse.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Vital Signs (Pulse)
|
-9.5 Beats per minute (beats/min)
Standard Deviation 15.7
|
1.8 Beats per minute (beats/min)
Standard Deviation 21.9
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Negative (Baseline)
|
23 Participants
|
22 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Trace (Baseline)
|
2 Participants
|
4 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Negative (Week 104)
|
18 Participants
|
16 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Trace (Week 104)
|
7 Participants
|
8 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 1+ (Week 104)
|
0 Participants
|
2 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 2+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 3+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Negative (Baseline)
|
25 Participants
|
26 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Trace (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Negative (Week 104)
|
25 Participants
|
26 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Trace (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 1+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 2+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 3+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Negative (Baseline)
|
24 Participants
|
25 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Trace (Baseline)
|
1 Participants
|
1 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Negative (Week 104)
|
25 Participants
|
20 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Trace (Week 104)
|
0 Participants
|
5 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 1+ (Week 104)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 2+ (Week 104)
|
0 Participants
|
1 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 3+ (Week 104)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Prothrombin time
|
0.50 Second (sec)
Interval -1.8 to 2.3
|
0.80 Second (sec)
Interval -0.6 to 2.3
|
|
Change in Blood Coagulation Test (Prothrombin Time and APTT)
APTT
|
0.60 Second (sec)
Interval -4.0 to 4.7
|
0.25 Second (sec)
Interval -9.1 to 5.6
|
SECONDARY outcome
Timeframe: Baseline, week 104Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in ECG
Normal (Baseline)
|
15 Participants
|
14 Participants
|
|
Change in ECG
Abnormal NCS (Baseline)
|
10 Participants
|
12 Participants
|
|
Change in ECG
Abnormal CS (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in ECG
Normal (Week 104)
|
16 Participants
|
13 Participants
|
|
Change in ECG
Abnormal NCS (Week 104)
|
9 Participants
|
13 Participants
|
|
Change in ECG
Abnormal CS (Week 104)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Height SDS (Japanese National Reference Data)
|
0.85 Standard deviation score
Standard Deviation 0.60
|
1.84 Standard deviation score
Standard Deviation 0.70
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Height SDS (Noonan Syndrome Reference Data in Japanese)
|
0.96 Standard deviation score
Standard Deviation 0.47
|
1.92 Standard deviation score
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: Week 104 to week 156Population: FAS.
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. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity
|
5.77 cm/year
Standard Deviation 1.26
|
7.01 cm/year
Standard Deviation 1.12
|
SECONDARY outcome
Timeframe: Week 156 to week 208Population: FAS.
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. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity
|
5.64 cm/year
Standard Deviation 1.23
|
6.11 cm/year
Standard Deviation 1.28
|
SECONDARY outcome
Timeframe: Week 104 to week 156Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity SDS
|
-0.39 Standard deviation score
Standard Deviation 1.61
|
1.44 Standard deviation score
Standard Deviation 1.25
|
SECONDARY outcome
Timeframe: Week 156 to week 208Population: FAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Height Velocity SDS
|
-0.73 Standard deviation score
Standard Deviation 1.52
|
0.92 Standard deviation score
Standard Deviation 1.69
|
SECONDARY outcome
Timeframe: Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period)Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Incidence of Treatment Emergent AEs
|
507 Events
|
539 Events
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in IGF-I
|
133.5 ng/mL
Standard Deviation 97.6
|
217.2 ng/mL
Standard Deviation 91.1
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
Change from baseline (within 4 weeks prior to week 0) in HbA1c was evaluated after 208 weeks of treatment.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in HbA1c
|
0.19 Percentage of HbA1c
Standard Deviation 0.13
|
0.20 Percentage of HbA1c
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - erythrocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Erythrocytes)
|
0.121 10^12 cells/L
Standard Deviation 0.328
|
0.095 10^12 cells/L
Standard Deviation 0.204
|
SECONDARY outcome
Timeframe: Baseline, Week 208Population: SAS. Number analyzed = participants with available data.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - leukocytes and thrombocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Leukocytes
|
-1.50 10^9 cells/L
Standard Deviation 2.22
|
-1.50 10^9 cells/L
Standard Deviation 1.57
|
|
Change in Clinical Laboratory Tests (Haematology: Leukocytes and Thrombocytes)
Thrombocytes
|
-27.5 10^9 cells/L
Standard Deviation 55.5
|
-56.6 10^9 cells/L
Standard Deviation 58.5
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haemoglobin. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Haemoglobin)
|
0.46 mmol/L
Standard Deviation 0.58
|
0.46 mmol/L
Standard Deviation 0.35
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - haematocrit. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Haematocrit)
|
1.24 Percentage of red blood cells
Standard Deviation 2.45
|
1.26 Percentage of red blood cells
Standard Deviation 1.63
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - neutrophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Neutrophils)
|
-1.23 Percentage of neutrophils
Standard Deviation 10.80
|
4.88 Percentage of neutrophils
Standard Deviation 9.41
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - lymphocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Lymphocytes)
|
-0.14 Percentage of lymphocytes
Standard Deviation 8.88
|
-5.70 Percentage of lymphocytes
Standard Deviation 8.86
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - monocytes. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Monocytes)
|
0.08 Percentage of monocytes
Standard Deviation 1.21
|
0.56 Percentage of monocytes
Standard Deviation 1.18
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - eosinophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Eosinophils)
|
1.30 Percentage of eosinophils
Standard Deviation 3.57
|
0.42 Percentage of eosinophils
Standard Deviation 1.44
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in haematological parameter - basophils. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Haematology: Basophils)
|
-0.01 Percentage of basophils
Standard Deviation 0.26
|
-0.12 Percentage of basophils
Standard Deviation 0.26
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
Total cholesterol
|
0.031 mmol/L
Standard Deviation 0.639
|
-0.110 mmol/L
Standard Deviation 0.609
|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
LDL cholesterol
|
-0.005 mmol/L
Standard Deviation 0.550
|
-0.173 mmol/L
Standard Deviation 0.523
|
|
Change in Clinical Laboratory Tests (Lipids: Total Cholesterol, LDL Cholesterol and HDL Cholesterol)
HDL cholesterol
|
0.036 mmol/L
Standard Deviation 0.275
|
0.056 mmol/L
Standard Deviation 0.173
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
AST
|
-5.4 U/L
Standard Deviation 2.4
|
-7.4 U/L
Standard Deviation 5.2
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
ALT
|
-1.28 U/L
Standard Deviation 2.65
|
-1.81 U/L
Standard Deviation 4.42
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
r-GTP
|
1.0 U/L
Standard Deviation 1.6
|
-3.5 U/L
Standard Deviation 22.8
|
|
Change in Clinical Laboratory Tests (Biochemistry: AST, ALT, r-GTP and Alkaline Phosphatase)
Alkaline phosphatase
|
113.9 U/L
Standard Deviation 126.4
|
84.8 U/L
Standard Deviation 140.9
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
Change from baseline (within 4 weeks prior to week 0) in biochemical parameter - total protein. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Total Protein)
|
0.02 g/dL
Standard Deviation 0.33
|
0.05 g/dL
Standard Deviation 0.37
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Blood urea nitrogen
|
-0.10 mmol/L
Standard Deviation 0.52
|
-0.15 mmol/L
Standard Deviation 0.53
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Sodium
|
0.9 mmol/L
Standard Deviation 2.1
|
1.4 mmol/L
Standard Deviation 2.5
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Potassium
|
-0.13 mmol/L
Standard Deviation 0.28
|
-0.09 mmol/L
Standard Deviation 0.38
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Chloride
|
-0.3 mmol/L
Standard Deviation 2.2
|
-0.2 mmol/L
Standard Deviation 2.2
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Total calcium
|
-0.02 mmol/L
Standard Deviation 0.07
|
-0.00 mmol/L
Standard Deviation 0.08
|
|
Change in Clinical Laboratory Tests (Biochemistry: Blood Urea Nitrogen, Sodium, Potassium, Chloride, Total Calcium and Phosphorus)
Phosphorus
|
0.036 mmol/L
Standard Deviation 0.111
|
0.111 mmol/L
Standard Deviation 0.103
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
Change from baseline (within 4 weeks prior to week 0) in biochemical parameters - creatinine. Missing values were imputed using the LOCF method.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Clinical Laboratory Tests (Biochemistry: Creatinine)
|
5.5 umol/L
Standard Deviation 4.4
|
6.7 umol/L
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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'.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Glucose Tolerance (AUC of Glucose) Based on the OGTT
|
1.03 Ratio of AUC
Geometric Coefficient of Variation 12.34
|
1.10 Ratio of AUC
Geometric Coefficient of Variation 14.55
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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'.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Glucose Tolerance (AUC of Insulin) Based on the OGTT
|
1.52 Ratio of AUC
Geometric Coefficient of Variation 49.97
|
2.38 Ratio of AUC
Geometric Coefficient of Variation 47.04
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Bone Age
|
3.89 Years
Standard Deviation 1.35
|
4.68 Years
Standard Deviation 1.11
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Bone Age/Chronological Age
|
0.049 Ratio (bone age/chronological age)
Standard Deviation 0.159
|
0.149 Ratio (bone age/chronological age)
Standard Deviation 0.151
|
SECONDARY outcome
Timeframe: Week 104, week 156Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Yearly Change in Bone Age/Change in Chronological Age
|
0.94 Ratio (bone age/chronological age)
Standard Deviation 0.70
|
0.97 Ratio (bone age/chronological age)
Standard Deviation 0.56
|
SECONDARY outcome
Timeframe: Week 156, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Yearly Change in Bone Age/Change in Chronological Age
|
0.87 Ratio (bone age/chronological age)
Standard Deviation 0.55
|
1.05 Ratio (bone age/chronological age)
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Diastolic blood pressure
|
5.8 mmHg
Standard Deviation 13.4
|
3.5 mmHg
Standard Deviation 8.4
|
|
Change in Vital Signs (Diastolic Blood Pressure and Systolic Blood Pressure)
Systolic blood pressure
|
6.8 mmHg
Standard Deviation 11.9
|
5.8 mmHg
Standard Deviation 16.1
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS. Number analyzed = participants with available data.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Vital Signs (Pulse)
|
-15.3 beats/min
Standard Deviation 14.2
|
-3.8 beats/min
Standard Deviation 16.5
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Negative (Baseline)
|
23 Participants
|
22 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Trace (Baseline)
|
2 Participants
|
4 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Negative (Week 208)
|
17 Participants
|
18 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: Trace (Week 208)
|
8 Participants
|
7 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 1+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 2+ (Week 208)
|
0 Participants
|
1 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Protein: 3+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Negative (Baseline)
|
25 Participants
|
26 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Trace (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Negative (Week 208)
|
25 Participants
|
26 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: Trace (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 1+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 2+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Glucose: 3+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Negative (Baseline)
|
24 Participants
|
25 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Trace (Baseline)
|
1 Participants
|
1 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 1+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 2+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 3+ (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Negative (Week 208)
|
24 Participants
|
22 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: Trace (Week 208)
|
1 Participants
|
2 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 1+ (Week 208)
|
0 Participants
|
1 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 2+ (Week 208)
|
0 Participants
|
0 Participants
|
|
Change in Urinalysis (Protein, Glucose and Occult Blood)
Occult blood: 3+ (Week 208)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in Blood Coagulation Test (Prothrombin Time and APTT)
Prothrombin time
|
0.70 sec
Interval -0.3 to 2.4
|
1.20 sec
Interval -0.2 to 2.2
|
|
Change in Blood Coagulation Test (Prothrombin Time and APTT)
APTT
|
0.70 sec
Interval -5.3 to 5.0
|
0.80 sec
Interval -7.4 to 6.4
|
SECONDARY outcome
Timeframe: Baseline, week 208Population: SAS.
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.
Outcome measures
| Measure |
NN-220 0.033 mg/kg/Day
n=25 Participants
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).
|
NN-220 0.066 mg/kg/Day
n=26 Participants
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).
|
|---|---|---|
|
Change in ECG
Normal (Baseline)
|
15 Participants
|
14 Participants
|
|
Change in ECG
Abnormal NCS (Baseline)
|
10 Participants
|
12 Participants
|
|
Change in ECG
Abnormal CS (Baseline)
|
0 Participants
|
0 Participants
|
|
Change in ECG
Normal (Week 208)
|
20 Participants
|
16 Participants
|
|
Change in ECG
Abnormal NCS (Week 208)
|
5 Participants
|
9 Participants
|
|
Change in ECG
Abnormal CS (Week 208)
|
0 Participants
|
1 Participants
|
Adverse Events
0.033 mg/kg/Day
Serious events: 9 serious events
Other events: 24 other events
Deaths: 0 deaths
0.066 mg/kg/Day
Serious events: 10 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
0.033 mg/kg/Day
n=25 participants at risk
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).
|
0.066 mg/kg/Day
n=26 participants at risk
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).
|
|---|---|---|
|
Congenital, familial and genetic disorders
Arnold-Chiari malformation
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Ear and labyrinth disorders
Conductive deafness
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Congenital, familial and genetic disorders
Craniosynostosis
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Dental caries
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Nervous system disorders
Febrile convulsion
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Congenital, familial and genetic disorders
Hamartoma
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Psychiatric disorders
Head banging
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Congenital, familial and genetic disorders
Phimosis
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Pneumonia
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Pneumonia mycoplasmal
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Polymyositis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Surgical and medical procedures
Pulmonary artery therapeutic procedure
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Salivary gland calculus
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Supernumerary teeth
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Reproductive system and breast disorders
Testicular swelling
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Velopharyngeal incompetence
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
Other adverse events
| Measure |
0.033 mg/kg/Day
n=25 participants at risk
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).
|
0.066 mg/kg/Day
n=26 participants at risk
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).
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 10 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 8 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
12.0%
3/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Psychiatric disorders
Attention deficit/hyperactivity disorder
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Bronchitis
|
16.0%
4/25 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
26.9%
7/26 • Number of events 12 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Bronchitis bacterial
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Chillblains
|
8.0%
2/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Conjunctivitis
|
20.0%
5/25 • Number of events 6 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
23.1%
6/26 • Number of events 6 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Eye disorders
Conjunctivitis allergic
|
24.0%
6/25 • Number of events 11 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Contusion
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
24.0%
6/25 • Number of events 8 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Dental caries
|
16.0%
4/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
15.4%
4/26 • Number of events 11 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Diarrhoea
|
28.0%
7/25 • Number of events 12 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
12.0%
3/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
30.8%
8/26 • Number of events 13 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Enteritis
|
8.0%
2/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.0%
3/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Gastroenteritis
|
32.0%
8/25 • Number of events 14 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
53.8%
14/26 • Number of events 33 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Gingivitis
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Nervous system disorders
Headache
|
24.0%
6/25 • Number of events 10 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Hordeolum
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Metabolism and nutrition disorders
Hyperinsulinaemia
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Impetigo
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Influenza
|
80.0%
20/25 • Number of events 34 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
69.2%
18/26 • Number of events 31 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 10 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Molluscum contagiosum
|
12.0%
3/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Nasopharyngitis
|
76.0%
19/25 • Number of events 115 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
80.8%
21/26 • Number of events 121 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Nausea
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Otitis media
|
28.0%
7/25 • Number of events 9 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
30.8%
8/26 • Number of events 9 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Otitis media acute
|
16.0%
4/25 • Number of events 6 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Pharyngitis
|
8.0%
2/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 6 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Pharyngitis streptococcal
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
General disorders
Pyrexia
|
36.0%
9/25 • Number of events 24 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
34.6%
9/26 • Number of events 12 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.0%
3/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Rhinitis
|
4.0%
1/25 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
15.4%
4/26 • Number of events 7 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
16.0%
4/25 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
15.4%
4/26 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
8.0%
2/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Immune system disorders
Seasonal allergy
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
3.8%
1/26 • Number of events 1 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Sinusitis
|
20.0%
5/25 • Number of events 14 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 6 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Streptococcal infection
|
8.0%
2/25 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 4 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
0.00%
0/26 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Tinea pedis
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 9 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/25 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Upper respiratory tract infection
|
32.0%
8/25 • Number of events 38 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
34.6%
9/26 • Number of events 43 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
28.0%
7/25 • Number of events 35 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
34.6%
9/26 • Number of events 30 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
20.0%
5/25 • Number of events 8 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
7.7%
2/26 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Infections and infestations
Varicella
|
8.0%
2/25 • Number of events 2 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
19.2%
5/26 • Number of events 5 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
|
Gastrointestinal disorders
Vomiting
|
16.0%
4/25 • Number of events 9 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
11.5%
3/26 • Number of events 3 • Week 0 to week 234 (208 weeks treatment period + 26 weeks extended treatment period) + 7 days (follow-up period).
All presented AEs are TEAEs. A TEAE (for the entire trial) 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 trial product administration. Results are based on the SAS, which included all participants receiving at least one dose of trial product.
|
Additional Information
Clinical Reporting Anchor and Disclosure (1452)
Novo Nordisk A/S
Phone: (+1) 866-867-7178
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
- Publication restrictions are in place
Restriction type: OTHER