Trial Outcomes & Findings for Efficacy and Safety of Recombinant Human Growth Hormone on Height Velocity in Subjects With Idiopathic Short Stature (NCT NCT01778023)

NCT ID: NCT01778023

Last Updated: 2017-06-02

Results Overview

Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Ht-V was calculated by Novo Nordisk.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 54 participants
• Primary outcome timeframe: After 6 months of treatment
• Results posted on: 2017-06-02

Participant Flow

The trial was conducted at 10 sites in Korea.

Participant milestones

Measure	Group A: 12-month GH Treatment For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Overall Study STARTED	36	18
Overall Study Exposed	36	15
Overall Study COMPLETED	36	15
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Measure	Group A: 12-month GH Treatment For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Overall Study Withdrawal by Subject	0	3

Baseline Characteristics

Efficacy and Safety of Recombinant Human Growth Hormone on Height Velocity in Subjects With Idiopathic Short Stature

Baseline characteristics by cohort

Measure	Group A: 12-month GH Treatment n=36 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Total n=51 Participants Total of all reporting groups
Age, Continuous	6.3 years STANDARD_DEVIATION 1.5 • n=5 Participants	5.9 years STANDARD_DEVIATION 1.2 • n=7 Participants	6.2 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	6 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	9 Participants n=7 Participants	28 Participants n=5 Participants
Height	107.7 cm STANDARD_DEVIATION 8.7 • n=5 Participants	105.8 cm STANDARD_DEVIATION 7.5 • n=7 Participants	107.1 cm STANDARD_DEVIATION 8.3 • n=5 Participants

PRIMARY outcome

Timeframe: After 6 months of treatment

Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B. Four (4) subjects had missing height at baseline visit.

Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Ht-V was calculated by Novo Nordisk.

Outcome measures

Measure	Group A: 12-month GH Treatment n=32 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Height Velocity (Ht-V)	12.02 cm/year Standard Error 0.29	6.87 cm/year Standard Error 0.43

SECONDARY outcome

Timeframe: After 6 months of treatment.

Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B. Four (4) subjects had missing height at baseline visit.

Height standard deviation scores (HSDS) were calculated using Korean growth data (reported by the Korea Centre for Disease Control and Prevention). The mean normal range for HSDS is from -2 to +2. Negative scores below -2 indicate a height below normal range, whereas positive scores above +2 indicate a height above normal.

Outcome measures

Measure	Group A: 12-month GH Treatment n=32 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Change in Ht-SDS (Height Standard Deviation Score)	0.76 Standard Deviation Score (SDS) Standard Error 0.04	0.19 Standard Deviation Score (SDS) Standard Error 0.06

SECONDARY outcome

Timeframe: After 6 months of treatment.

Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.

IGF-I (insulin-like growth factor-1) was measured at Visit 1 (screening),Visit 3 (3 months ± 7 days ),Visit 4 (6 months ± 7 days),Visit 5 (9 months ± 7 days ) and Visit 6 (12 months ± 7 days ). Change of IGF-I from baseline to 6 months treatment was calculated.

Outcome measures

Measure	Group A: 12-month GH Treatment n=36 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Change in IGF Related Factors: IGF-I (Insulin-like Growth Factor-I)	192.58 ng/ml Standard Error 14.00	28.03 ng/ml Standard Error 21.81

SECONDARY outcome

Timeframe: After 6 months of treatment.

Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.

IGFBP-3 was measured at Visit 1(screening), Visit 3 (3 months ± 7 days ), Visit 4 (6 months ± 7 days), 5 (9 months ± 7 days ) and 6 ( 12 months ± 7 days). Change of IGFBP-3 from baseline to 6 months treatment were calculated.

Outcome measures

Measure	Group A: 12-month GH Treatment n=36 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Change in IGF Related Factors: IGFBP-3 (Insulin-like Growth Factor Binding Protein-3)	0.89 mcg/mL Standard Error 0.19	0.22 mcg/mL Standard Error 0.30

SECONDARY outcome

Timeframe: After 6 months of treatment.

Population: Safety analysis set (SAS) :includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.

Change in bone age from the baseline to 6 months.

Outcome measures

Measure	Group A: 12-month GH Treatment n=36 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Change in Bone Age	0.5 years Standard Deviation 0.2	0.5 years Standard Deviation 0.2

SECONDARY outcome

Timeframe: Throughout the trial (12 months)

Population: Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.

AEs were collected throughout the trial in both groups.

Outcome measures

Measure	Group A: 12-month GH Treatment n=36 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 Participants Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Occurrence of Adverse Events	70 events	25 events

SECONDARY outcome

Timeframe: At the first 6 months and the last 6 months in group A

Population: Full analysis set (FAS) - included all randomised subjects in Group A who received at least one dose of the trial product and all randomised subjects in Group B.

Height velocity (Ht-V) (cm/year) is the change in height per year (after 6 months of treatment). Three sort of Ht-V was calculated from height data at Visit 2 (day 0), 4 (6 months ± 7 days) and 6 (12 months ± 7 days), as follows: Between Visits 2 and 4, between Visit 4 and 6 and between Visit 2 and 6. Ht-V was calculated by Novo Nordisk. It is the difference between Ht-V for the last 6 months and Ht-V for the first 6 months of treatment. This endpoint was only evaluated for Group A as per the trial protocol.

Outcome measures

Measure	Group A: 12-month GH Treatment n=32 Participants For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Ht-V (Height Velocity)	2.80 cm/year Interval 1.55 to 4.04	—

Adverse Events

Group A: 12-month GH Treatment

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Group B: 6-month Untreated + 6-month GH Treatment

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Group A: 12-month GH Treatment n=36 participants at risk For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 participants at risk Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Congenital, familial and genetic disorders Hydrocele	2.8% 1/36 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Pharyngotonsillitis	2.8% 1/36 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Pneumonia	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	2.8% 1/36 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Vascular disorders Kawasaki's disease	2.8% 1/36 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.

Other adverse events

Measure	Group A: 12-month GH Treatment n=36 participants at risk For 12 months, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.	Group B: 6-month Untreated + 6-month GH Treatment n=15 participants at risk Subjects participated in the trial for 12 months. For the first six months of the trial period, subjects were untreated. For the last six months of the trial period, a weekly dosage of 0.469 mg of somatropin (hGH) per kg of body weight was injected subcutaneously in the evening in seven (7) days per week using the Norditropin® Nordilet®.
Ear and labyrinth disorders Eye disorder	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
General disorders Chest pain	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
General disorders Pyrexia	5.6% 2/36 • Number of events 2 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Conjunctivitis	2.8% 1/36 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Influenza	8.3% 3/36 • Number of events 3 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Nasopharyngitis	41.7% 15/36 • Number of events 43 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	46.7% 7/15 • Number of events 14 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Rhinitis	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	13.3% 2/15 • Number of events 3 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Infections and infestations Upper respiratory tract	8.3% 3/36 • Number of events 3 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/36 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	6.7% 1/15 • Number of events 1 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.
Skin and subcutaneous tissue disorders Urticaria	8.3% 3/36 • Number of events 3 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.	0.00% 0/15 Safety analysis set - includes all subjects in Group A receiving at least one dose of the trial product and all subjects in Group B who had any available data after Visit 2.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee Novo Nordisk reserves the right to not release data until specified milestones, e.g. when the clinical trial report is available. At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
• Publication restrictions are in place

Restriction type: OTHER