E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted SDS < -1) in short children born small for gestational age (SGA), with a birth weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth (height velocity (HV) SDS < 0 during the last year) by 4 years of age or later |
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E.1.1.1 | Medical condition in easily understood language |
Short children born small for gestational age |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018747 |
E.1.2 | Term | Growth hormone |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
evaluation of the long-term effect of growth hormone treatment on the development of diabetes during the treatment period in short children born SGA |
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E.2.2 | Secondary objectives of the trial |
• report the incidence of anti-rhGH antibodies during treatment • evaluation of the efficacy (with respect to changes in height parameters) of Omnitrope® treatment in short children born SGA • evaluation of IGF-I and IGFBP-3 levels during treatment • evaluation of incidence and severity of adverse events
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pre-pubertal (Tanner stage I) children born SGA • Boys: equal or above 4 years of age (bilateral testicular volume < 4 ml) • Girls: equal or above 4 years of age (bilateral Tanner breast stage 1) 2. Growth disturbance defined as current height SDS < -2.5 (and parental adjusted SDS < -1) for chronological age and sex according to country specific references. If country specific references are not available, pre-defined published references will be used. 3. Birth weight and/or length below -2 SD for gestational age (according to country specific references). For the evaluation of gestational age, the date of the last menstrual period or ultrasonographic data obtained during the pregnancy should be used. If country specific references are not available, pre-defined published references will be used. 4. Height records between 18 months and 6 months prior to the start of GH treatment must be available. 5. Calculated height velocity SDS < 0 during the last year according to Prader 1989 6. Written informed consent of patient (for children who can read or understand) and parent or legal guardian
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E.4 | Principal exclusion criteria |
1. Onset of puberty 2. Closed epiphyses 3. Diabetes mellitus type I or type II 4. Fasting blood glucose equal or above 100 mg/dl (5.6 mmol/l) measured in venous blood sample 5. Abnormal findings in OGTT defined by equal or above 140 mg/dl (7.8 mmol/l) after 120 minutes 6. Known IGF-I level above +2SD for sex and age 7. 8. Acute critical illness e.g. suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure. 9. Known to be hepatitis B or hepatitis C positive or HIV-positive, known to have advanced diseases such as AIDS or tuberculosis 10. Any other disease, genetic disorder or malformation or treatment known to be associated with growth retardation, e.g. Turner or Noonan syndrome, Laron syndrome, Russell-Silver syndrome, Prader-Willi syndrome, skeletal dysplasias, chronic renal failure, cystic fibrosis, heart and liver diseases, malabsorption (coeliac disease), malnutrition, patients receiving radiation therapy of head or spinal cord 11. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin 12. Known or suspected hypersensitivity to rhGH or any of the excipients (e.g. benzyl alcohol) 13. Previous treatment with any hGH preparation 14. Oral, inhalative or parenteral treatment with glucosteroids, except for physiological replacement, or hypothyroidism which has been left untreated, or was inadequately treated, or treated for less than 3 months 15. Treatment with LHRH / gonadotropin releasing hormone (GnRH) analoga (e.g. triptorelin) 16. Treatment with antidiabetic medication (e.g. metformin, insulin) 17. Drug abuse, substance abuse, or alcohol abuse 18. Known to be immunocompromised 19. Intake of growth promoting medication, e.g. anabolic steroids 20. Use of other investigational drugs within 30 days of enrolment 21. Patients unwilling and/or parents/guardians who are not capable of ensuring compliance with the provisions of the study protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints: - Carbohydrate metabolism: Fasting plasma glucose and insulin levels will be measured at baseline, at 6 and 12 months, then annually during Omnitrope® treatment, and at the end of treatment. Glycosylated haemoglobin (HbA1C) will be measured at baseline, at 6 and 12 months and then annually during Omnitrope® treatment, and at the end of treatment. An oral glucose tolerance test (OGTT) will be performed at baseline, at 6 and 12 months and then annually during Omnitrope® treatment, and at the end of treatment. - Immunogenicity Anti-rhGH antibodies and E. coli host cell peptide (HCP) antibodies will be measured at baseline, at 3, 6, 9, 12, 18 and 24 months, then annually during Omnitrope® treatment, and at the end of treatment. - Safety lab / urine analysis Hematology, blood chemistry and urine analysis will be measured at baseline, at 6 and 12 months, then annually during Omnitrope® treatment, and at the end of treatment. - (Serious) Adverse events: Adverse events will be collected throughout the study. - Vital signs / weight: Vital signs (blood pressure, pulse) as well as weight and pubertal status will be examined at each visit. BMI will be calculated at each visit.
Efficacy endpoints: - Auxological: Height, height SDS, height velocity and height velocity SDS will be monitored at baseline, at every 3 months during Omnitrope® treatment and at the end of treatment. - Pharmacodynamic: IGF-I and IGFBP-3 serum levels will be assessed at baseline, at 3, 6, 9 and 12 months, then bi-annually during Omnitrope® treatment, and at the end of treatment. - Bone age: Bone age readings will be performed at baseline (if historical (screening) X-ray dates older than six months), at the end of each treatment year and at the end of treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim analyses are planned at the following time points:
• 2022 with data of patients who completed 1 year of follow-up
• 2026 with data of patients who completed 5 years of follow-up
• 2031 with data of patients who completed 10 years of follow-up
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Subjects will be followed for 10 years after the end of treatment according to Protocol.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 15 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 15 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |