Clinical Trial Results:
Long-term safety follow-up after growth hormone Treatment (rhGH) of short children born Small for Gestational Age (SGA)
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Summary
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EudraCT number |
2007-001364-72 |
Trial protocol |
HU DE CZ PL |
Global end of trial date |
31 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2019
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First version publication date |
15 May 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EP00-402
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01491854 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Hexal AG / Sandoz
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Sponsor organisation address |
Industriestr. 25, Holzkirchen, Germany, 83807
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Oct 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this study was to monitor short children born SGA who participated in study EP00-401 for the development of diabetes for a further 10 years after termination of rhGH treatment and to report the incidence of anti-rhGH antibodies (ADA) for 6 months after termination of
rhGH treatment.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jul 2009
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Czech Republic: 8
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Country: Number of subjects enrolled |
Georgia: 9
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Poland: 91
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Country: Number of subjects enrolled |
Romania: 8
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Worldwide total number of subjects |
118
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EEA total number of subjects |
109
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
13
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Adolescents (12-17 years) |
99
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Adults (18-64 years) |
6
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
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 | ||||||||||||||||
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Pre-assignment
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Screening details |
SAF : safety Analysis set FAS : full Analysis set | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Blinding implementation details |
NA
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Arms
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Arm title
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Monitoring of long-term safety | ||||||||||||||||
Arm description |
Long-term safety follow-up after the end of treatment with Omnitrope (single arm) | ||||||||||||||||
Arm type |
safety follow up | ||||||||||||||||
Investigational medicinal product name |
omnitrope
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
not applicable : this was an observational follow-up study without intake of any investigational drug or control Treatment.
Investigational drug was given in EP00-401 trial, and the experimental product given in the EP00-401 iis detailed here.
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Baseline characteristics reporting groups
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Reporting group title |
Monitoring of long-term safety
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Reporting group description |
Long-term safety follow-up after the end of treatment with Omnitrope (single arm) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Monitoring of long-term safety
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Reporting group description |
Long-term safety follow-up after the end of treatment with Omnitrope (single arm) | ||
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End point title |
Evaluate the long-term effect of growth hormone treatment on the development of diabetes after end of therapy. [1] | ||||||
End point description |
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
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End point type |
Primary
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End point timeframe |
5 years
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was performed |
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| No statistical analyses for this end point | |||||||
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End point title |
To evaluate the long term effects of rhGH on carbohydrate metabolism through fasting plasma glucose (FPG) Levels [2] | ||||||||||||||||
End point description |
Supportive to Primary Endpoint
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End point type |
Primary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was performed |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
To evaluate the long term effects of rhGH on carbohydrate metabolism through fasting Insulin levels [3] | ||||||||||||||||
End point description |
Supportive to Primary Endpoint
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End point type |
Primary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was performed |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
To evaluate the long term effects of rhGH on carbohydrate metabolism through glucose glycolsylated hemoglobin (HbA1c) [4] | ||||||||||||||||
End point description |
Supportive to Primary Endpoint
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End point type |
Primary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was performed |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
To evaluate the long term effects of rhGH on carbohydrate metabolism through HOMA and QUICKI scores [5] | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was performed |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
to evaluate IGF-I and IGFBP-3 levels for 10 years after end of growth hormone treatment | ||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
baseline, 6 months, 1 year , 5 years
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
To evaluate the incidence of anti-rhGH antibodies after 6 months after termination of growth hormone treatment. | ||||||||||||||
End point description |
number of participants with positive results for anti-drug antibody (ADA). Percentages indicated are calculated based on the total number of patients (118 participants).
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End point type |
Secondary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
to evaluate final height | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
baseline, 6 months, 1 year, 5 years
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
approximately 9 years
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Adverse event reporting additional description |
AE additional description
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Total
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Reporting group description |
Total | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Mar 2012 |
the main purpose of this amendement was to modify the inclusion criteria and the visit schedule and assessments |
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09 May 2012 |
This amendment aims to refrain from further assessment of host cell protein (HCP). |
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06 Jun 2013 |
This amendment aims to document changes regarding requirements for safety monitoring and harmonization of safety related sections in the protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated prematurely in accordance with the request to close study EP00-402 “EMEA/H/C/000607/MEA 10.2” submitted to the EMA on 29-Mar-2018 and adopted by the EMA on 28-Jun-2018 | |||
