E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Kabuki Syndrome (KS, OMIM 147920) with a mutation in MLL2 gene. |
Kabuki Syndroom (KS, OMIM 147920) met een mutatie in MLL2 gen. |
|
E.1.1.1 | Medical condition in easily understood language |
Kabuki syndrome children. Some of the clinical signs and symptoms in KS children are obesity, hypertension, hypotonia and short stature. |
Kabuki Syndroom kinderen. Een deel van de klinische tekenen en symptomen bij KS kinderen zijn overgewicht, hoge bloeddruk, hypotonie en kleine gestalte. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
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 |
The primary objective of this study is to assess the relation between the short term metabolic changes after start of rhGH therapy and the long term change in height SDS after one year of treatment. |
Het primaire doel van deze studie is het beoordelen van de relatie tussen de korte termijn metabole veranderingen na start van rhGH therapie en de lange termijn verandering in de lengte SDS na een jaar behandeling. |
|
E.2.2 | Secondary objectives of the trial |
Secondly, we want to assess the effects of GH on metabolic risk parameters which are typical parameters for the metabolic syndrome in adults. |
Ten tweede willen we de effecten van GH te beoordelen op metabole risicofactoren parameters die kenmerkend zijn voor het metabool syndroom bij volwassenen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children with the MML2 mutation.
-Children who meet at least four out of five KS characteristics:
#Facial features: long palpebral fissures with eversion of outer third, arched eyebrows with sparse outer half, prominent and/or misshapen ears, and depressed nasal tip.
#Skeletal abnormalities.
#Intellectual disability (mild to moderate).
#Postnatal short stature.
#Abnormalities of dermal ridges.
-Informed consent.
-Age ≥ four years.
|
-Kinderen met de MML2 mutatie.
-Kinderen die aan ten minste vier van de vijf KS kenmerken:
# Facial eigenschappen: lange oogspleten met eversie van de buitenste derde, gebogen wenkbrauwen met spaarzame buitenste helft, opvallende en / of misvormde oren, neus en naar beneden hangende tip.
# Skeletafwijkingen.
# Verstandelijke handicap (licht tot matig).
# Postnatale klein gestalte.
#Abnormale dermatoglyfen.
-Informed consent.
-Leeftijd ≥ vier jaar. |
|
E.4 | Principal exclusion criteria |
-Children with a chronological or bone age greater than 8 years for girls and 10 years for boys, because of the influence of puberty.
-Extremely low dietary intake (less than minimal required intake for age according to WHO criteria).
-Use of medication that might interfere with growth during GH therapy, such as corticosteroids and sex steroids.
|
-Kinderen met een chronologische of bot leeftijd hoger dan 8 jaar voor meisjes en 10 jaar voor jongens, vanwege de invloed van de puberteit.
-Extreem lage inname via de voeding (minder dan minimaal benodigde inname voor leeftijd volgens WHO-criteria).
-Gebruik van medicatie die kunnen interfereren met de groei tijdens de GH therapie, zoals corticosteroïden en geslachtshormonen. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Is there an increase in TEE during 6 weeks treatment with rhGH in children with Kabuki Syndrome?
What is the relation between the short-term (6 weeks) change in TEE as measured with the DLW technique and the long term change in height SDS during treatment with rhGH?
What is the effect of rhGH treatment on metabolic risk parameters typical for the metabolic syndrome in adults? |
Is er een toename van de TEE gedurende 6 weken behandeling met groeihormoon bij kinderen met Kabuki syndroom?
Wat is de relatie tussen de korte termijn (6 weken) verandering in de TEE gemeten met de DLW techniek en de lange termijn verandering in de lengte SDS tijdens de behandeling met rhGH? |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Increase in TEE during 6 weeks treatment and the long term change in height SDS during treatment with rhGH after one year. |
Een toename van de TEE gedurende 6 weken behandeling met groeihormoon en de lange termijn verandering in de lengte SDS na een jaar. |
|
E.5.2 | Secondary end point(s) |
To assess the long (1 year) term safety of growth hormone therapy on metabolic risk parameters and body composition. |
Wat is het effect van de groeihormoon behandeling op metabole risicofactoren parameters typisch zijn voor het metabool syndroom bij volwassenen? |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After one year of treament with growth hormone. |
Na een jaar groeihormoon behandeling. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
|
The study period for each individual is 1 year, which will be for 1 year were included. The study ends when the last visit of the last subject is done. |
De studieduur voor ieder individu is 1 jaar, waarbij gedurende 1 jaar geincludeerd zal worden. De studie eindigd wanneer bij de laatste proefpersoon de laatste controle plaats vindt. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |