E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pre-pubertal drug naïve growth-deficient children with insufficient endogenous growth hormone secretion |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate that the LB03002 is clinically comparable to daily Genotropin® in terms of its safety and efficacy features. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Pre-pubertal children (boys age: > 3 and <12 years or girls: age >3 and <11 years) with isolated GH insufficiency, GH insufficiency as part of multiple pituitary hormone deficiencies, or organic GH insufficiency. If GH insufficiency occurred after treatment for any brain tumour, the patient has to be at least one year in clinical remission which has to be confirmed by computer tomography (CT) or magnetic resonance imaging (MRI) scan (with contrast) within 3 months prior to study entry Children with negative signs for intracranial tumour or tumour growth as confirmed with a CT or MRI scan (with contrast) within 12 months prior to inclusion or at inclusion visit Confirmed diagnosis of GH insufficiency as determined by two different GH provocation tests, defined as a peak plasma GH level of ≤7 ng/ml No prior exposure to rhGH therapy (GH-treatment naive) Height (HT), except in children suffering from organic GH insufficiency, of at least 2.0 standard deviations (SD) (HT SDS ≤-2.0) below the mean height for chronological age (CA) and sex according to the 2000 standards from the Centers for Disease Control and Prevention (CDC) (www.cdc.gov/growthcharts). Height velocity (HV) of at least 1 SD (HV SDS ≤-1) below the mean HV for CA and sex according to the standards of Prader et al (1989). The minimum time between two standard height measurements should be at least 6 month before inclusion. Baseline IGF-I level of at least 0.5 SD (IGF-1 SDS ≤-0.5) below the mean IGF-1 level standardised for age and sex according to the central laboratory reference values. Written informed consent of parent or legal guardian of subject |
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E.4 | Principal exclusion criteria |
Any clinically significant abnormality likely to affect growth or the ability to evaluate growth, such as, but not limited to, chronic diseases like renal insufficiency, spinal cord irradiation, and malnutrition (BMI must be above -2SD and below +2SD of mean BMI for the chronological age and sex according to the 2000 CDC standards, and albumin must be above lower limit of normal (LLN) of the central laboratory for a patient to be included). Patients with overt diabetes mellitus (Fasting blood sugar >126 mg/dl or 7 mmol/l) and impaired fasting sugar (Fasting blood sugar >100 mg/dl or 5.5 mmol/l after repeated blood analysis) Chromosomal abnormalities and medical "syndromes" (Turner's syndrome, Laron syndrome, Noonan syndrome or absence of growth hormone receptors), with the exception of septo-optic dysplasia Congenital abnormalities (causing skeletal abnormalities), Russell-Silver Syndrome, skeletal dysplasias Closed epiphyses Other growth promoting medication such as anabolic steroids, with the exception of pituitary hormone replacement therapy, thyroxine, hydrocortisone and desmopressin (DDAVP) replacement therapies Children requiring glucocorticoid therapy (e.g. asthma) that are on the dose of more than 400 µg/d of inhaled budesonide or equivalents inhaled for longer than 1 month during a calendar year Bone age (BA) higher than chronological age Poorly controlled or uncontrolled pituitary insufficiencies of other axes (e.g., thyroid-stimulating hormone, adrenocorticotropic hormone/cortisol, vasopressin deficiency): Children who are on stable replacement therapy for less than 6 months for thyroid replacement therapy, and less than 3 months for other hormonal deficiencies prior to enrolment Major medical conditions and/or presence of contraindication to rhGH treatment Known or suspected HIV-positive patient or patient with advanced diseases such as AIDS or tuberculosis Drug, substance, or alcohol abuse Known hypersensitivity to the components of study medication Evidence of tumour growth or malignant disease Presence of anti-hGH antibodies at screening The patient and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the height velocity (HV) at the end of 12 months treatment. The HV developed by patients treated with LB03002 will be compared to the control arm receiving daily dose of Genotropin® 0.03 mg/kg/day using non-inferiority tests.
Safety endpoints are: Incidence of adverse events after 1, 3, 6, 9, 12 months of treatment; Incidence of anti-hGH antibody formation after 1, 3, 6, 9, 12 months treatment; Incidence of anti-S. cerevisiae protein antibody formation after 1, 3, 6, 9, and 12 months treatment; Global tolerability assessment (investigator and patient) Investigator's local tolerability assessment; Subject's local tolerability assessment; IGF-I levels after 1, 3, 6, 9, 12 months treatment; IGFBP-3 levels after 1, 3, 6, 9, 12 months treatment; Difference of IGF-I SDS and IGFBP-3 SDS after 1, 3, 6, 9, 12 months treatment; Blood glucose, fasting insulin level, HbA1c, thyroid panel tests, lipid panel tests, cortisol levels after 1, 3, 6, 9, 12 months treatment; All other haematology and biochemical parameters after 3, 6, 9, 12 months treatment; Physical examination after 1, 3, 6, 9, 12 months treatment; Vital signs after 1, 3, 6, 9, 12 months treatment; |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Study end will be the finalisation of the Study Report, which is expected for March 2007. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |