Trial Outcomes & Findings for Long-term Safety Follow-up After Growth Hormone Treatment of Short Children Born Small for Gestational Age (NCT NCT01491854)
NCT ID: NCT01491854
Last Updated: 2019-08-14
Results Overview
Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria: * FPG ≥ 126 mg/dl (7.0 mmol/L) during blood sampling and/or during Oral Glucose Tolerance Test (OGTT) * 2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT * Investigator documenting diagnosis of diabetes mellitus type 2 during OGTT
Recruitment status
TERMINATED
Study phase
NA
Target enrollment
130 participants
Primary outcome timeframe
5 years
Results posted on
2019-08-14
Participant Flow
130 participants signed informed consent. Of the 130 enrolled subjects, 11 subjects had no post-baseline visit, leading to exclusion from the SAF/FAS. Another subject was excluded as he received treatment with Omnitrope, which was not consistent with the protocol. Accordingly, 118 subjects comprised the SAF and in the FAS
SAF : safety Analysis set FAS : full Analysis set
Participant milestones
| Measure |
Monitoring of Long-term Safety
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
Overall Study
STARTED
|
130
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
130
|
Reasons for withdrawal
| Measure |
Monitoring of Long-term Safety
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
Overall Study
mainly due to premature termination
|
93
|
|
Overall Study
Death
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Lost to Follow-up
|
33
|
Baseline Characteristics
full Analysis set
Baseline characteristics by cohort
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
Age, Continuous
|
14.79 years
STANDARD_DEVIATION 2.848 • n=5 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants • full Analysis set
|
|
Sex: Female, Male
Male
|
54 Participants
n=5 Participants • full Analysis set
|
|
Race/Ethnicity, Customized
Caucasian
|
118 Participants
n=5 Participants • FAS
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: full Analysis set
Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria: * FPG ≥ 126 mg/dl (7.0 mmol/L) during blood sampling and/or during Oral Glucose Tolerance Test (OGTT) * 2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT * Investigator documenting diagnosis of diabetes mellitus type 2 during OGTT
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
Evaluate the Long-term Effect of Growth Hormone Treatment on the Development of Diabetes After End of Therapy.
|
0 Participants
|
PRIMARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: safety Analysis set with measure
Supportive to Primary Endpoint
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels
FPG 6 months
|
-0.13 mmol/L
Standard Deviation 0.567
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels
FPG 1 year
|
-0.14 mmol/L
Standard Deviation 0.457
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels
FPG baseline
|
4.69 mmol/L
Standard Deviation 0.492
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels
FPG 5 years
|
-0.37 mmol/L
Standard Deviation 0.856
|
PRIMARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: full Analysis set with measure
Supportive to Primary Endpoint
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels
baseline
|
70.87 pmol/L
Standard Deviation 38.477
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels
6 months
|
-2.34 pmol/L
Standard Deviation 38.267
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels
1 year
|
-7.48 pmol/L
Standard Deviation 34.676
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels
5 years
|
3.40 pmol/L
Standard Deviation 52.526
|
PRIMARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: full Analysis set with measure
Supportive to Primary Endpoint
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c)
baseline
|
5.280 percentage
Standard Deviation 0.3569
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c)
6 months
|
-0.057 percentage
Standard Deviation 0.3621
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c)
1 year
|
-0.108 percentage
Standard Deviation 0.2931
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c)
5 years
|
-0.308 percentage
Standard Deviation 0.6036
|
PRIMARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: safety Analysis set with measure
Supportive to Primary Endpoint. HOMA = homeostasis model assessment for Insulin resistance: Healthy Range: 1.0 (0.5-1.4). \< 1.0 means you are insulin-sensitive which is optimal. \>1.9 indicates early insulin resistance. \> 2.9 indicates significant insulin resistance. The quantitative insulin sensitivity check index (QUICKI) measures insulin sensitivity, which is the inverse of insulin resistance. The QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. Lower numbers reflect greater insulin resistance.
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
HOMA score baseline
|
2.082 score on a scale
Standard Deviation 1.0336
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
HOMA score 6 months
|
-0.073 score on a scale
Standard Deviation 1.1447
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
HOMA score 1 year
|
-0.206 score on a scale
Standard Deviation 1.0170
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
HOMA score 5 years
|
0.094 score on a scale
Standard Deviation 1.8835
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
QUICKI score baseline
|
0.354 score on a scale
Standard Deviation 0.0459
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
QUICKI score 6 months
|
0.004 score on a scale
Standard Deviation 0.0350
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
QUICKI score 1 year
|
0.012 score on a scale
Standard Deviation 0.0413
|
|
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores
QUICKI score 5 years
|
0.022 score on a scale
Standard Deviation 0.0703
|
SECONDARY outcome
Timeframe: baseline, 6 months, 1 year , 5 yearsPopulation: full Analysis set, with measure
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGF-1 baseline
|
67.42 nmol/L
Standard Deviation 31.137
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGF-1 6 months
|
48.42 nmol/L
Standard Deviation 20.002
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGF-1 1 year
|
46.28 nmol/L
Standard Deviation 21.555
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGF-1 5 years
|
44.60 nmol/L
Standard Deviation 16.035
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGFBP-3 baseline
|
211.12 nmol/L
Standard Deviation 49.523
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGFBP-3 6 months
|
187.79 nmol/L
Standard Deviation 42.999
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGFBP-3 1 year
|
186.59 nmol/L
Standard Deviation 47.246
|
|
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment
IGFBP-3 5 years
|
180.00 nmol/L
Standard Deviation 26.470
|
SECONDARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: safety Analysis set
number of participants with positive results for anti-drug antibody (ADA). Percentages indicated are calculated based on the total number of patients (118 participants).
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment.
baseline
|
0 Participants
|
|
To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment.
6 months
|
1 Participants
|
|
To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment.
1 year
|
0 Participants
|
|
To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment.
5 years
|
0 Participants
|
SECONDARY outcome
Timeframe: baseline, 6 months, 1 year, 5 yearsPopulation: Full Analysis set with measure
Outcome measures
| Measure |
Monitoring of Long-term Safety
n=118 Participants
Long-term safety follow-up after the end of treatment with Omnitrope (single arm)
|
|---|---|
|
to Evaluate Final Height
baseline
|
152.63 cm
Standard Deviation 16.362
|
|
to Evaluate Final Height
6 months
|
152.41 cm
Standard Deviation 16.894
|
|
to Evaluate Final Height
1 year
|
152.43 cm
Standard Deviation 16.698
|
|
to Evaluate Final Height
5 years
|
150.42 cm
Standard Deviation 12.938
|
Adverse Events
Total
Serious events: 8 serious events
Other events: 23 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Total
n=118 participants at risk
Total
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Cardiac disorders
Arrhythmia
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Chronic tonsillitis
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Nasopharyngitis
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Pneumonia
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Sepsis
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Urinary tract infection
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Injury, poisoning and procedural complications
Head injury
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Nervous system disorders
Epilepsy
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Nervous system disorders
Syncope
|
1.7%
2/118 • approximately 9 years
AE additional description
|
|
Nervous system disorders
VIth nerve paralysis
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.85%
1/118 • approximately 9 years
AE additional description
|
|
Reproductive system and breast disorders
Oligomenorrhoea
|
0.85%
1/118 • approximately 9 years
AE additional description
|
Other adverse events
| Measure |
Total
n=118 participants at risk
Total
|
|---|---|
|
Endocrine disorders
Hypothyroidism
|
3.4%
4/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
7/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Pharyngitis
|
4.2%
5/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Respiratory tract infection
|
3.4%
4/118 • approximately 9 years
AE additional description
|
|
Infections and infestations
Upper respiratory tract infection
|
3.4%
4/118 • approximately 9 years
AE additional description
|
|
Nervous system disorders
Headache
|
2.5%
3/118 • approximately 9 years
AE additional description
|
|
Skin and subcutaneous tissue disorders
Acne
|
3.4%
4/118 • approximately 9 years
AE additional description
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER