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in accordance with the request to close study EP00-402 "EMEA/H/C/000607/MEA 10.2" submitted and adopted by the EMA
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This study is performed as part of the Marketing Authorisation Holder's post-marketing pharmacovigilance plan to investigate the long-term safety, in particular the diabetogenic potential and immunogenicity of rhGH therapy in short children born small for gestational age (SGA).
The purpose of this study is
to monitor short children born SGA who were treated with growth hormone in study EP00-401 for the development of diabetes for a further 10 years after termination of growth hormone treatment
and
to report the incidence of anti-rhGH antibodies and of E. coli host cell peptide (HCP) antibodies (ABs) for 6 months after termination of GH treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Monitoring of long-term safety | Other | Long-term safety follow-up after the end of treatment with Omnitrope (single arm) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bloodsampling | Other | Bloodsampling |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the Long-term Effect of Growth Hormone Treatment on the Development of Diabetes After End of Therapy. | Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria:
| 5 years |
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years |
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years |
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c) | Supportive to Primary Endpoint | baseline, 6 months, 1 year, 5 years |
| To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment | baseline, 6 months, 1 year , 5 years | |
| To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment. | 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sandoz Biopharmaceuticals Sandoz | Sandoz GmbH | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Ústí nad Labem | Czech Republic | 400 11 | Czechia | ||
| Novartis Investigative Site |
SAF : safety Analysis set FAS : full Analysis set
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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| ID | Title | Description |
|---|---|---|
| FG000 | Monitoring of Long-term Safety | Long-term safety follow-up after the end of treatment with Omnitrope (single arm) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 14, 2014 | Apr 29, 2019 |
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| baseline, 6 months, 1 year, 5 years |
| baseline, 6 months, 1 year, 5 years |
| to Evaluate Final Height | baseline, 6 months, 1 year, 5 years |
| Hradec Králové |
| 500 05 |
| Czechia |
| Novartis Investigative Site | Prague | 150 06 | Czechia |
| Novartis Investigative Site | Tbilisi | 144 | Georgia |
| Novartis Investigative Site | Nordrhein Westfalen | Sankt Augustin | 53757 | Germany |
| Novartis Investigative Site | München | 80337 | Germany |
| Novartis Investigative Site | Miskolc | 3526 | Hungary |
| Novartis Investigative Site | Poznai | Greater Poland Voivodeship | 60-572 | Poland |
| Novartis Investigative Site | Bydgoszcz | Kuyavian-Pomeranian Voivodeship | 85667 | Poland |
| Novartis Investigative Site | Wroclaw | Lower Silesian Voivodeship | 50-311 | Poland |
| Novartis Investigative Site | Wroclaw | Lower Silesian Voivodeship | 50-368 | Poland |
| Novartis Investigative Site | Rzeszów | Podkarpackie Voivodeship | 35-301 | Poland |
| Novartis Investigative Site | Katowice | Silesian Voivodeship | 40-752 | Poland |
| Novartis Investigative Site | Zabrze | Silesian Voivodeship | 41-800 | Poland |
| Novartis Investigative Site | Gdansk | 80 952 | Poland |
| Novartis Investigative Site | Krakow | 30-663 | Poland |
| Novartis Investigative Site | Lodz | 93-338 | Poland |
| Novartis Investigative Site | Szczecin | 71-252 | Poland |
| Novartis Investigative Site | Warsaw | 04 730 | Poland |
| Novartis Investigative Site | Kielce | Świętokrzyskie Voivodeship | 25734 | Poland |
| Novartis Investigative Site | Lasi | Iaşi | 700111 | Romania |
| Novartis Investigative Site | Bucharest | 20395 | Romania |
| Novartis Investigative Site | Cluj-Napoca | CLUJ | Romania |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Monitoring of Long-term Safety | Long-term safety follow-up after the end of treatment with Omnitrope (single arm) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | full Analysis set | Count of Participants | Participants |
| |||||||||||||||||
| Race/Ethnicity, Customized | FAS | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Evaluate the Long-term Effect of Growth Hormone Treatment on the Development of Diabetes After End of Therapy. | Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria:
| full Analysis set | Posted | Count of Participants | Participants | 5 years |
|
|
| ||||||||||||||||||||||||||
| Secondary | to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment | full Analysis set, with measure | Posted | Mean | Standard Deviation | nmol/L | baseline, 6 months, 1 year , 5 years |
|
|
| ||||||||||||||||||||||||||
| Secondary | To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment. | number of participants with positive results for anti-drug antibody (ADA). Percentages indicated are calculated based on the total number of patients (118 participants). | safety Analysis set | Posted | Count of Participants | Participants | No | baseline, 6 months, 1 year, 5 years |
|
| ||||||||||||||||||||||||||
| Primary | To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels | Supportive to Primary Endpoint | safety Analysis set with measure | Posted | Mean | Standard Deviation | mmol/L | baseline, 6 months, 1 year, 5 years |
|
| ||||||||||||||||||||||||||
| Primary | To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels | Supportive to Primary Endpoint | full Analysis set with measure | Posted | Mean | Standard Deviation | pmol/L | baseline, 6 months, 1 year, 5 years |
|
| ||||||||||||||||||||||||||
| Primary | To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c) | Supportive to Primary Endpoint | full Analysis set with measure | Posted | Mean | Standard Deviation | percentage | baseline, 6 months, 1 year, 5 years |
|
| ||||||||||||||||||||||||||
| Secondary | to Evaluate Final Height | Full Analysis set with measure | Posted | Mean | Standard Deviation | cm | baseline, 6 months, 1 year, 5 years |
|
|
| ||||||||||||||||||||||||||
| Primary | To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores | 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. | safety Analysis set with measure | Posted | Mean | Standard Deviation | score on a scale | baseline, 6 months, 1 year, 5 years |
|
|
approximately 9 years
AE additional description
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Total | Total | 1 | 118 | 8 | 118 | 23 | 118 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Chronic tonsillitis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (19.1) | Systematic Assessment |
| |
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| VIth nerve paralysis | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Oligomenorrhoea | Reproductive system and breast disorders | MedDRA (19.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypothyroidism | Endocrine disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (19.1) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (19.1) | Systematic Assessment |
|
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
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharma AG | 862-778-8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 28, 2018 | Apr 29, 2019 | SAP_001.pdf |
| Categories |
|---|
| IGF-1 baseline |
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| IGF-1 6 months |
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| IGF-1 1 year |
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| IGF-1 5 years |
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| IGFBP-3 baseline |
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| IGFBP-3 6 months |
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| IGFBP-3 1 year |
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| IGFBP-3 5 years |
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|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| FPG baseline |
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| ||||
| FPG 6 months |
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| FPG 1 year |
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| FPG 5 years |
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| Title | Denominators | Categories |
|---|
| baseline |
|
| ||||
| 6 months |
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| 1 year |
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| 5 years |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| baseline |
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| ||||
| 6 months |
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| 1 year |
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| 5 years |
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| baseline |
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| 6 months |
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| 1 year |
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| 5 years |
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