E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Monocarboxylate Transporter 8 (MCT8) deficiency |
deficit del trasportatore 8 dei monocarbossilati (MCT8) |
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E.1.1.1 | Medical condition in easily understood language |
MCT 8 deficiency or AHDS (Allan-Herndon-Dudley syndrome) |
deficit MCT8 o sindrome di Allan-Herndon-Dudley |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10078564 |
E.1.2 | Term | Thyroid stimulating hormone deficiency |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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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 |
To evaluate the effects of tiratricol treatment on neurodevelopment in young MCT8 deficiency patients as measured by the Gross Motor Function Measure 88 (GMFM-88). |
Valutare gli effetti di tiratricol sul neurosviluppo in pazienti in età evolutiva con deficit di MCT8, misurata in base alla scala Gross Motor Function Measure (GMFM-88). |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the effect of tiratricol treatment on specific Motor Development milestones by individual item scores in the Gross Motor Function Measure test.
2) To evaluate the effect of tiratricol treatment on neurodevelopment in young MCT8 deficient patients as measured by the Bayley Scales of Infant Development (BSID-III).
3) Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features (serum T3 concentrations, tissue specific markers of thyroid hormone action). |
1. Valutare l'effetto del trattamento con tiratricol su specifici traguardi di sviluppo motorio in base ai punteggi individuali nel test Gross Motor Function Measure 2. Valutare l'effetto del trattamento con tiratricol sul neurosviluppo in base alle Bayley Scales of Infant Development (BSID-III) 3. Valutare l'effetto di tiratricol sulle caratteristiche tireotossiche cliniche e biochimiche (concentrazioni sieriche di T3, marcatori tessutali specifici dell'azione dell'ormone tiroideo). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent form from the parents or legal guardian. 2. Parents stated willingness to comply with all study procedures and availability for the duration of the study. 3. The participant should be aged between 0 and 30 months on the day of inclusion. 4. The participant should have a pathogenic mutation in the MCT8 gene.
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1. Modulo di consenso informato firmato e datato dai genitori o dal tutore legale. 2. I genitori hanno volontariamente dichiarato di rispettare tutte le procedure di studio e di essere disponibili per tutta la durata dello studio. 3. Il partecipante deve avere un'età compresa tra 0 e 30 mesi, al giorno dell'inclusione. 4. Il partecipante dovrebbe presentare una mutazione patogena nel gene MCT8. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with tiratricol. 2. Previous treatment with a combination of Propylthiouracil (PTU) and Levothyroxine (LT4). 3. Previous treatment with LT4 for a longer period than three months. 4. Treatment with LT4 within three months of baseline visit. 5. Major illness or recent major surgery (within four weeks of baseline visit 1) unrelated to MCT8 deficiency. 6. Known allergic reactions to components of the IMP. 7. Treatment with another investigational drug or participation in other interventional trial within three months prior to baseline visit 1. 8. Patients that have any contra-indication for tiratricol treatment as stated in the Investigators Brochure. |
1. Trattamento precedente con tiratricol. 2. Trattamento precedente con una combinazione di propiltiouracile (PTU) e levotiroxina (LT4). 3. Trattamento precedente con LT4 per un periodo più lungo di tre mesi. 4. Trattamento con LT4 entro tre mesi dalla visita basale. 5. Malattia grave o recente intervento chirurgico maggiore (entro quattro settimane dalla visita basale 1) non correlato al deficit di MCT8. 6. Reazioni allergiche note ai componenti dell'IMP. 7. Trattamento con un altro farmaco sperimentale o partecipazione ad altri studi interventistici entro tre mesi prima della visita basale 1. 8. Pazienti che hanno controindicazioni per il trattamento con tiratricol come indicato nell'Investigators brochure |
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E.5 End points |
E.5.1 | Primary end point(s) |
GMFM-88 score compared to natural history GMFM-88 scores from untreated patients. |
Punteggio GMFM-88 rispetto allo storico dei punteggi GMFM-88 di pazienti non trattati. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment. |
Dopo 24 mesi di trattamento rispetto al basale. Un'analisi intermedia verrà effettuata dopo 12 mesi di trattamento. |
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E.5.2 | Secondary end point(s) |
1) Gross Motor Function Measure test (GMFM-88) individual item score 10 and 24 compared to natural history scores from untreated patients. 2) Age equivalent (AE) score from the BSID compared to natural history AE scores from untreated patients. 3) Serum T3 (efficacy), peripheral thyroid hormone TH status (serum SHBG; serum creatine kinase, creatinine, blood pressure and body weight) (efficacy). |
1. Punteggi individuali GMFM-88 per le voci 10 e 24 rispetto allo storico dei punteggi di pazienti non trattati. 2. Punteggio equivalente di età (AE) dal BSID rispetto allo storico dei punteggi AE di pazienti non trattati 3. T3 sierico (efficacia), stato dell'ormone tiroideo periferico (SHBG sierico; creatina chinasi sierica, creatinina, pressione sanguigna e peso corporeo) (efficacia). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment. |
Dopo 24 mesi di trattamento rispetto al basale. Un'analisi intermedia verrà effettuata dopo 12 mesi di trattamento. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Tiratricol will be administered to all patients, orally in an individual dose titrated based on seru |
Tiratricol will be administered to all patients, orally in an individual dose titrated based on seru |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Tiratricol verrà somministrato a tutti i pazienti, per via orale in una singola dose titolata in bas |
Tiratricol will be administered to all patients, orally in an individual dose titrated based on seru |
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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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
United States |
France |
Germany |
Italy |
Netherlands |
United Kingdom |
Czechia |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |